Subarachnoid blood acutely induces spreading depolarizations and early cortical infarction.

See Ghoshal and Claassen (doi:10.1093/brain/awx226) for a scientific commentary on this article. Early cortical infarcts are common in poor-grade patients after aneurysmal subarachnoid haemorrhage. There are no animal models of these lesions and mechanisms are unknown, although mass cortical spreading depolarizations are hypothesized as a requisite mechanism and clinical marker of infarct development. Here we studied acute sequelae of subarachnoid haemorrhage in the gyrencephalic brain of propofol-anaesthetized juvenile swine using subdural electrode strips (electrocorticography) and intraparenchymal neuromonitoring probes. Subarachnoid infusion of 1­2 ml of fresh blood at 200 µl/min over cortical sulci caused clusters of spreading depolarizations (count range: 12­34) in 7/17 animals in the ipsilateral but not contralateral hemisphere in 6 h of monitoring, without meaningful changes in other variables. Spreading depolarization clusters were associated with formation of sulcal clots (P < 0.01), a high likelihood of adjacent cortical infarcts (5/7 versus 2/10, P < 0.06), and upregulation of cyclooxygenase-2 in ipsilateral cortex remote from clots/infarcts. In a second cohort, infusion of 1 ml of clotted blood into a sulcus caused spreading depolarizations in 5/6 animals (count range: 4­20 in 6 h) and persistent thick clots with patchy or extensive infarction of circumscribed cortex in all animals. Infarcts were significantly larger after blood clot infusion compared to mass effect controls using fibrin clots of equal volume. Haematoxylin and eosin staining of infarcts showed well demarcated zones of oedema and hypoxic-ischaemic neuronal injury, consistent with acute infarction. The association of spreading depolarizations with early brain injury was then investigated in 23 patients [14 female; age (median, quartiles): 57 years (47, 63)] after repair of ruptured anterior communicating artery aneurysms by clip ligation (n = 14) or coiling (n = 9). Frontal electrocorticography [duration: 54 h (34, 66)] from subdural electrode strips was analysed over Days 0­3 after initial haemorrhage and magnetic resonance imaging studies were performed at ∼ 24­48 h after aneurysm treatment. Patients with frontal infarcts only and those with frontal infarcts and/or intracerebral haemorrhage were both significantly more likely to have spreading depolarizations (6/7 and 10/12, respectively) than those without frontal brain lesions (1/11, P's < 0.05). These results suggest that subarachnoid clots in sulci/fissures are sufficient to induce spreading depolarizations and acute infarction in adjacent cortex. We hypothesize that the cellular toxicity and vasoconstrictive effects of depolarizations act in synergy with direct ischaemic effects of haemorrhage as mechanisms of infarct development. Results further validate spreading depolarizations as a clinical marker of early brain injury and establish a clinically relevant model to investigate causal pathologic sequences and potential therapeutic interventions.

Fractures in Spinal Ankylosing Disorders: A Narrative Review of Disease and Injury Types, Treatment Techniques, and Outcomes.

INTRODUCTION: Spinal ankylosing disorders encompass ankylosing spondylitis (AS), disseminated hyperostosis of the spine, and end-stage spondylosis. All these result in a stiffened and frequently deformed spinal column. This makes the spinal column highly susceptible to severe injuries that are commonly associated with unfavorable outcomes. Improved understanding of the underlying disease processes and clinical comorbidities may alter the poor injury related morbidity and mortality outcomes. METHODS: A systematic review of the MEDLINE and PubMed databases was performed using the following key words to identify articles published between 2001 and 2016: "ankylosing spondylitis," "epidemiology," "DISH," "treatment," "outcome," and/or "fracture." Articles were read for data on methodology (retrospective vs. prospective), type of treatment, number of patients, mean patient age, and mean follow-up. RESULTS: Twenty-one identified articles were analyzed. Average age was 63.4 years. Most patients were men. Ground level fall or low energy trauma caused most injuries. Diagnosis was delayed in 15%-41% cases. Hyperextension fracture patterns were most common. Cervical spine fractures were more common than thoracolumbar fractures, with the highest prevalence between C5 and C7. Neurologic deficits were encountered in 21%-100% of patients. Operative fixation and fusion were performed in 40%-100% of patients. Mortality was reported between 0% and 32% at 1 year postinjury. Complications were encountered in 84% of patients, mostly in the form of pneumonia, respiratory failure, and pseudoarthrosis. Neurologic deterioration has been reported in 16% of patients. Fusion was successful in 87%-100% of patients. Neurologic deficits improved in function in 6%-66% at the final follow-up. CONCLUSIONS: Because of the stiffening of the spinal column, patients with spinal ankylosing disorders are preferably evaluated for spinal fractures and ligamentous injuries after even trivial trauma. Spinal injuries in patients with AS are difficult to diagnose on plain radiographs; computed tomography and magnetic resonance imaging are recommended instead. The entire spine should be scanned for multilevel involvement. Although osteoporosis makes fixation of spine implants a significant concern, the literature has reported that most patients with AS treated surgically had good outcomes. Numerous studies have reported risks associated with conservative management.

Vertebral Osteomyelitis Due to Granulicatella Adiacens, a Nutritionally Variant Streptococci.

Vertebral osteomyelitis is a common pathology affecting the spine. We present the case of a 46-year-old male who was diagnosed with progressive L2 vertebral osteomyelitis due to a rare pathogen, Granulicatella adiacens. Granulicatella adiacens is part of the normal body flora and is often difficult to culture on traditional mediums. The patient required a lateral corpectomy and posterior fixation for spinal stabilization and source control.

Prosthetic treatment of hip fractures in the elderly patient.

As the elderly population in our society significantly increases, the incidence of displaced femoral neck fractures will increase proportionally. Three surgical procedures are available to treat such fractures: internal fixation, hemiarthroplasty (unipolar or bipolar), and total hip arthroplasty. Long-term costs and efficacy of these three procedures vary, primarily due to postoperative complications. Thus, it is imperative that all surgeons conduct a proper preoperative evaluation of each patient before choosing the optimal treatment plan. Internal fixation has been shown to be more beneficial for physiologically younger patients who sustain displaced femoral neck fractures. However, the choice between hemiarthroplasty and total hip arthroplasty in the geriatric patient remains difficult. This article aims to provide a practical algorithm for the treatment of these patients.

Brachyury expression in tailless Molgulid ascidian embryos.

The T-box transcription factor gene Brachyury is important for the differentiation of notochord in all chordates, including the ascidians Halocynthia roretzi and Ciona intestinalis. We isolated Brachyury from molgulid ascidians, which have evolved tailless larvae multiple times independently, and found the genes appear functional by cDNA sequence analyses. We then compared the expression of Mocu-Bra in tailed Molgula oculata embryos to two tailless species, Molgula occulta (Mocc-Bra) and Molgula tectiformis (Mt-Bra). Here we show that both tailless species express Brachyury in the notochord lineage during embryogenesis. Initial expression of Mocu-Bra is normal in tailed M. oculata embryos; 10 precursor notochord cells divide twice to result in 40 notochord cells that converge and extend to make a notochord down the center of the tail. In contrast, in tailless Molgula occulta, Mocc-Bra expression disappears prematurely, and there is only one round of division, resulting in 20 cells in the final notochord lineage that never converge or extend. In M. occulta x M. oculata hybrid embryos, expression of Mocu-Bra is prolonged, and the embryos form a tail with 20 notochord cells that converge and extend normally. However, in Molgula tectiformis, a different tailless ascidian, Mt-Bra was expressed only in the 10 notochord precursor cells, which never divide, converge, or extend. In summary, neither Brachyury function nor the early establishment of the notochord lineage appears to be impaired in tailless embryos. In light of these results, we are continuing to investigate how and why notochord development is lost in tailless molgulid ascidian embryos.