D. Andrew Wilkinson

Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy

Conventional methods for intraoperative histopathologic diagnosis are labour- and time-intensive, and may delay decision-making during brain-tumour surgery. Stimulated Raman scattering (SRS) microscopy, a label-free optical process, has been shown to rapidly detect brain-tumour infiltration in fresh, unprocessed human tissues. Here, we demonstrate the first application of SRS microscopy in the operating room by using a portable fibre-laser-based microscope and unprocessed specimens from 101 neurosurgical patients. We also introduce an image-processing method – stimulated Raman histology (SRH) – which leverages SRS images to create virtual haematoxylin-and-eosin-stained slides, revealing essential diagnostic features. In a simulation of intraoperative pathologic consultation in 30 patients, we found a remarkable concordance of SRH and conventional histology for predicting diagnosis (Cohens kappa, κ > 0.89), with accuracy exceeding 92%. We also built and validated a multilayer perceptron based on quantified SRH image attributes that predicts brain-tumour subtype with 90% accuracy. Our findings provide insight into how SRH can now be used to improve the surgical care of brain tumour patients.

Early Open and Endovascular Thoracic Aortic Repair for Complicated Type B Aortic Dissection

BACKGROUND Aortic repair for acute (<2 weeks) or subacute (2 to 8 weeks) type B dissection is performed for rupture, impending rupture, or malperfusion. Thoracic aortic endovascular repair (TEVAR) has been suggested as a more suitable, less invasive alternative to open descending aortic repair for type B dissection, but a comparative analysis is warranted. METHODS Seventy-three patients with type B dissection (1995 to 2012) underwent early open descending aortic repair (n = 24) or TEVAR (n = 49). Mean age was 66.3 years. Intervention occurred in the acute (n = 53) or subacute (n = 20) period for malperfusion (n = 8), rupture (n = 22), or factors portending rupture, including rapid expansion (n = 26), uncontrolled pain (n = 18), aortic size greater than 5.0 cm (n = 26), or refractory hypertension (n = 2). Twenty-six had multiple indications. Patients undergoing TEVAR were older and had an increased incidence of coronary artery disease and renal impairment (all p < 0.05). RESULTS Thirty-day mortality was 12% (n = 9). Morbidity included stroke (n = 7), dialysis (n = 6), paralysis (n = 4), and tracheostomy (n = 7). A composite outcome of mortality and these morbidities independently correlated with presentation with frank rupture (p < 0.01) or limb ischemia (p = 0.03), but not treatment strategy (p = 0.3). Ten-year Kaplan-Meier survival was 57.5% and similar between groups (p = 0.74). Independent predictors of late mortality included perioperative stroke and presentation with rupture during late follow-up (both p < 0.02). Five-year freedom from aortic reintervention or rupture was similar between TEVAR (80.0%) and open descending aortic repair (82.8%; p = 0.45). CONCLUSIONS Early aortic repair for complicated type B dissection is associated with high rates of morbidity, late mortality, and reintervention. Despite its use in a higher risk group, outcomes seen with TEVAR were similar to open repair, thus supporting the recent paradigm shift toward an endovascular approach.

Intraventricular Hemorrhage: the Role of Blood Components in Secondary Injury and Hydrocephalus

Intraventricular hemorrhage (IVH) is characterized by an influx of blood into the ventricles of the brain. It has a highly morbid prognosis and develops in more than 12,000 premature infants every year in the USA [1, 2]. Within the last two decades, about 31 % of successfully resuscitated very preterm infants—born prior to 30-week gestational age—experienced IVH, one third of which were of grade 3 or 4 severity [3]. Furthermore, the incidence of severe IVH has increased over the last 20 years. In addition to the severe neurological deficits associated with the disease, high-grade IVH can lead to posthemorrhagic hydrocephalus (PHH), with 48 % of patients sustaining grades 3 and 4 IVH developing PHH. When combined, IVH-PHH is a dauntingly critical condition, and one whose pathology is not completely understood. In addition to infants, IVH is also seen in patients with intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), two major types of hemorrhagic stroke with high morbidity and mortality [4–10]. IVH occurs in up to 50 % of patients with primary ICH and 45 % of patients with aneurysmal SAH [11–13]. Recent studies have found IVH is a predictor of poor outcome after ICH [11, 12]. The international surgical trial in intracerebral hemorrhage showed that in ICH patients, IVH lowers the rate of favorable outcomes and is associated with hydrocephalus in more than 50 % of adult patients [11]. IVH is also an independent prognostic factor for poor outcome in SAH patients, and acute hydrocephalus occurs in 20–30 % of such patients [13]. In addition, blood in the ventricle may contribute to hydrocephalus after traumatic brain injury [14]. Despite this, there is a scarcity of research into the field of IVH when compared to ICH or SAH. Studies of ICH and SAH have shown increasing recognition of the importance of particular blood components in brain damage [6, 15–17]. Although the body of literature regarding the role of blood components in IVH is far smaller than in ICH or SAH, a similar focus is apparent—the roles of hemoglobin and its degradation products, plasma components and the coagulation cascade, platelets, and leukocytosis in the pathogenesis of IVH are becoming more apparent (Fig. 1).

Injury mechanisms in acute intracerebral hemorrhage

ABSTRACT Intracerebral hemorrhage (ICH) is the most common hemorrhagic stroke subtype, and rates are increasing with an aging population. Despite an increase in research and trials of therapies for ICH, mortality remains high and no interventional therapy has been demonstrated to improve outcomes. We review known mechanisms of injury, recent clinical trial results, and newly discovered signaling pathways involved in hematoma clearance. Enthusiasm remains high for methods of minimally invasive clot removal as well as pharmacologic strategies to improve recovery after ICH, both of which are currently being evaluated in clinical trials. This article is part of the Special Issue entitled ‘Cerebral Ischemia’. HighlightsIntracerebral hemorrhage remains a deadly hemorrhagic stroke subtype.Trials of interventional strategies have failed to show a beneficial effect.Multiple trials of minimally invasive clot removal strategies are underway.Studies of hematoma clearance mechanisms may reveal pharmacologic targets.

The choroid plexus as a site of damage in hemorrhagic and ischemic stroke and its role in responding to injury

While the impact of hemorrhagic and ischemic strokes on the blood–brain barrier has been extensively studied, the impact of these types of stroke on the choroid plexus, site of the blood-CSF barrier, has received much less attention. The purpose of this review is to examine evidence of choroid plexus injury in clinical and preclinical studies of intraventricular hemorrhage, subarachnoid hemorrhage, intracerebral hemorrhage and ischemic stroke. It then discusses evidence that the choroid plexuses are important in the response to brain injury, with potential roles in limiting damage. The overall aim of the review is to highlight deficiencies in our knowledge on the impact of hemorrhagic and ischemic strokes on the choroid plexus, particularly with reference to intraventricular hemorrhage, and to suggest that a greater understanding of the response of the choroid plexus to stroke may open new avenues for brain protection.

Trends in surgical treatment of Chiari malformation Type I in the United States

OBJECTIVE The goal of this analysis was to define temporal and geographic trends in the surgical treatment of Chiari malformation Type I (CM-I) in a large, privately insured health care network. METHODS The authors examined de-identified insurance claims data from a large, privately insured health care network of over 58 million beneficiaries throughout the United States for the period between 2001 and 2014 for all patients undergoing surgical treatment of CM-I. Using a combination of International Classification of Diseases (ICD) diagnosis codes and Current Procedural Terminology (CPT) codes, the authors identified CM-I and associated diagnoses and procedures over a 14-year period, highlighting temporal and geographic trends in the performance of CM-I decompression (CMD) surgery as well as commonly associated procedures. RESULTS There were 2434 surgical procedures performed for CMD among the beneficiaries during the 14-year interval; 34% were performed in patients younger than 20 years of age. The rate of CMD increased 51% from the first half to the second half of the study period among younger patients (p < 0.001) and increased 28% among adult patients between 20 and 65 years of age (p < 0.001). A large sex difference was noted among adult patients; 78% of adult patients undergoing CMD were female compared with only 53% of the children. Pediatric patients undergoing CMD were more likely to be white with a higher household net worth. Regional variability was identified among rates of CMD as well. The average annual rate of surgery ranged from 0.8 surgeries per 100,000 insured person-years in the Pacific census division to 2.0 surgeries per 100,000 insured person-years in the East South Central census division. CONCLUSIONS Analysis of a large nationwide health care network showed recently increasing rates of CMD in children and adults over the past 14 years.

Penetrating Head Injury by a Nail Gun: Case Report, Review of the Literature, and Management Considerations

Our objective is to discuss penetrating head injuries (PHIs) which, although rare, lead to considerable morbidity and mortality. One of the most significant culprits of PHI is the nail gun, which was introduced in 1959 and has gained substantial popularity. We describe our successful strategy for removing an 8-cm nail that penetrated through the orbit and middle cranial fossa, with the tip lodged within the posterior fossa. Vascular imaging and balloon test occlusion are imperative in circumstances where vessel sacrifice is necessary. In addition, positioning of balloons within large vessels that are in close proximity to the penetrating object is necessary to control bleeding that may occur during removal of the object. It is of paramount importance to have a multidisciplinary team participating in the management and eventual removal of foreign objects within the intracranial compartment. Included is a review of the literature and a discussion on management approaches to such injuries.

Aggressive Myeloid Sarcoma Causing Recurrent Spinal Cord Compression

OBJECTIVE Myeloid sarcoma is a rare extramedullary solid tumor comprised of immature myeloid precursor cells, most commonly associated with acute myelogenous leukemia (AML). We present the case of a patient with a history of Shwachman-Diamond syndrome and AML who presented with myeloid sarcoma causing acute spinal cord compression. CASE DESCRIPTION The patient was a 20-year-old man who presented with acute onset weakness and numbness in his lower extremities. Magnetic resonance imaging revealed a thoracic dorsal epidural mass. Despite the history of AML, we elected to forego image-guided biopsy and up-front radiation due to the rapidly progressive nature of his myelopathy. Immediate surgical decompression was performed, but the patient had recurrence of tumor leading to further compression 13 days postoperatively. Subsequently, emergent radiation was performed, leading to resolution of cord compression and local disease control. CONCLUSIONS To our knowledge, there are no randomized controlled trials examining the appropriate timing for postoperative radiation. Because most typical neuro-oncologic cases have no need for immediate postoperative radiation, our practice has been to wait 14 days to initiate postoperative radiation to ensure wound healing. One unique feature of our case was the rapid recurrence of symptoms due to tumor progression. Given this observation, we believe that radiation therapy should be considered as soon as possible after confirmatory pathology diagnosis for patients presenting with neurological compromise due to myeloid sarcoma of the spine.

Impact of Weekend Presentation on Short-Term Outcomes and Choice of Clipping vs Coiling in Subarachnoid Hemorrhage.

BACKGROUND Presentation on a weekend is commonly associated with higher mortality and a decreased likelihood of receiving invasive procedures. OBJECTIVE To determine whether weekend presentation influences mortality, discharge destination, or type of treatment received (clip vs coil) in subarachnoid hemorrhage (SAH). METHODS We performed a serial cross-sectional retrospective study using the Nationwide Inpatient Sample. All adult discharges with a primary diagnosis of SAH (ICD-9-CM 435) from 2005 to 2010 were included, and records with trauma or arteriovenous malformation were excluded. Unadjusted and adjusted associations between weekend presentation and 3 outcomes (in-hospital mortality, discharge destination, and treatment with clip vs coil) were estimated using chi-square tests and multilevel logistic regression. RESULTS A total of 46 093 admissions for nontraumatic SAH were included in the sample; 24.6% presented on a weekend, 68.9% on a weekday, and 6.5% had unknown day of presentation. Weekend admission was not a significant predictor of inpatient mortality (25.4% weekend vs 24.9% weekday; P = .44), or a combined poor outcome measure of mortality or discharge to long-term acute care or hospice (30.3% weekend vs 29.4% weekday; P = .23). Among those treated for aneurysm obliteration, the proportion of clipped vs coiled did not change with weekend vs weekday presentation (21.5% clipped with weekend presentation vs 21.6% weekday, P = .95; 21.5% coiled with weekend presentation vs 22.4% weekday, P = .19). CONCLUSION Presentation with nontraumatic SAH on a weekend did not influence mortality, discharge destination, or type of treatment received (clip vs coil) compared with weekday presentation.

Early initiation of chemoradiation following index craniotomy is associated with decreased survival in high-grade glioma

The Stupp protocol of post-resection external beam radiation therapy and concomitant temozolomide is the standard of care for patients with newly-diagnosed glioblastoma, with expanded use in anaplastic astrocytoma. However, the optimal interval between surgery and these adjuvant therapies, and its impact on survival, is unknown. To investigate this, de-identified claims from a large, private health insurance database were queried to identify adult patients who underwent index craniotomy for resection of a supratentorial neoplasm during the period 2005–2014 and began postoperative radiation and temozolomide within 13 weeks of surgery. A total of 2535 patients were assigned to groups based on interval from surgery to first radiation treatment of up to 4 weeks, 4–6 weeks, or 6–13 weeks. Of these, 1098 patients began radiation treatment within 4 weeks of craniotomy, 1019 between 4 and 6 weeks, and 418 between 6 and 13 weeks. There was significant regional variation in treatment schedule in the United States. Survival was calculated based on time from first craniotomy to death. Kaplan–Meier plot and multivariate Cox proportional hazard regression demonstrated a statistically significant association between earliest postoperative radiation and decreased survival (hazard ratio 1.31), along with older age and male sex. Earlier initiation of postoperative radiation for high-grade glioma is not associated with increased survival. Rather, beginning radiation treatment within 4 weeks of craniotomy was associated with significantly worse survival compared to initiation of treatment 4–13 weeks after craniotomy. This is the largest population-based study to date regarding timing of Stupp protocol initiation.