24/7/365 Neuroradiologist Coverage Improves Resident Perception of Educational Experience, Referring Physician Satisfaction, and Turnaround Time.

PURPOSE: To quantitatively and qualitatively assess the impact of attending neuroradiology coverage on radiology resident perceptions of the on-call experience, referring physician satisfaction, and final report turnaround times. MATERIALS AND METHODS: 24/7/365 attending neuroradiologist coverage began in October 2016 at our institution. In March 2017, an online survey of referring physicians, (emergency medicine, neurosurgery, and stroke neurology) and radiology residents was administered at a large academic medical center. Referring physicians were queried regarding their perceptions of patient care, report accuracy, timeliness, and availability of attending radiologists before and after the implementation of overnight neuroradiology coverage. Radiology residents were asked about their level of independence, workload, and education while on-call. Turnaround time (TAT) was measured over a 5-month period before and after the implementation of overnight neuroradiology coverage. RESULTS: A total of 28 of 64 referring physicians surveyed responded, for a response rate of 67%. Specifically, 19 of 23 second (junior resident on-call) and third year radiology residents (senior resident on-call) replied, 4 of 4 stroke neurology fellows replied, 8 of 21 neurosurgery residents, and 16 of 39 emergency medicine residents replied. Ninety-five percent of radiology residents stated they had adequate independence on call, 100% felt they have enough faculty support while on call, and 84% reported that overnight attending coverage has improved the educational value of their on-call experience. Residents who were present both before and after the implementation of TAT metrics thought their education, and independence had been positively affected. After overnight neuroradiology coverage, 85% of emergency physicians perceived improved accuracy of reports, 69% noted improved timeliness, and 77% found that attending radiologists were more accessible for consultation. The surveyed stroke neurology fellows and neurosurgery residents reported positive perception of the TAT, report quality, and availability of accessibility of attending radiologist. CONCLUSIONS: In concordance with prior results, overnight attending coverage significantly reduced turnaround time. As expected, referring physicians report increased satisfaction with overnight attending coverage, particularly with respect to patient care and report accuracy. In contrast to some prior studies, radiology residents reported both improved educational value of the on-call shifts and preserved independence. This may be due to the tasking the overnight neuroradiology attending with dual goals of optimized TAT, and trainee growth. Unique implementation including subspecialty trained attendings may facilitate radiology resident independence and educational experience with improved finalized report turnaround.

Diagnostic Performance of Glymphatic System Evaluation Using Diffusion Tensor Imaging in Idiopathic Normal Pressure Hydrocephalus and Mimickers.

PURPOSE: To investigate the pathological change of the glymphatic system in idiopathic normal pressure hydrocephalus (iNPH) using diffusion tensor imaging (DTI) analysis. MATERIALS AND METHODS: 24 right-handed patients were referred to our hydrocephalus clinic for assessment of ventriculomegaly and gait impairment. 12 of 24 were diagnosed as pseudo-iNPH (piNPH) based on assessment by a neurologist. Diffusivity maps in the direction of the x-axis (right-to-left) (Dx), y-axis (anterior-to-posterior) (Dy), and z-axis (inferior-to-superior) (Dz) were computed. The diffusion map was coregistered to International Consortium for Brain Mapping (ICBM) DTI-81 atlas. The analysis along the perivascular space (ALPS) index was defined as mean (Dxpro, Dypro)/mean (Dypro, Dzasc), where Dxpro and Dxasc are Dx values in the projection and association fiber areas, respectively. Evans index and callosal angle were also assessed on each case. RESULTS: ALPS indexes of the control, piNPH, and iNPH cases were 1.18 ± 0.08, 1.08 ± 0.03, and 0.94 ± 0.06, respectively, and there were significant differences among the groups (control vs. piNPH, P = 0.003; control vs. iNPH P < 0.001; piNPH vs. iNPH, P < 0.001). Area under curve (AUC) was 0.92, 1.00, and 1.00 on control vs. piNPH, control vs. iNPH, and piNPH vs. iNPH on ROC analysis. Between piNPH and NPH, ALPS index has higher diagnostic performance than Evans index and callosal angle (AUC = 1.00 vs. 0.84, P = 0.028; AUC = 1.00 vs. 0.74, P = 0.016). CONCLUSION: Atlas-based ALPS index using the DTI method differentiated among iNPH, piNPH, and controls clearly.

Incidental finding of tumor while investigating subarachnoid hemorrhage: ethical considerations and practical strategies.

High-resolution neuroimaging modalities are used often in studies involving healthy volunteers. Subsequently, a significant increase in the incidental discovery of asymptomatic intracranial abnormalities raised the important ethical issues of when follow-up and treatment may be necessary. We examined the literature to establish a practical set of criteria for approaching incidental findings. Our objective is to develop an algorithm for when follow-up may be important and to provide recommendations that would increase the likelihood of follow-up. A systematic literature search was performed using the PubMed and MEDLINE databases to identify articles describing brain tumors and intracranial aneurysms. The treatment algorithm we present suggests that incidental intracranial masses suspicious for glioma should be biopsied or resected, while other masses are to be followed with serial imaging based on the expected growth pattern. Lack of follow-up can result in adverse outcomes that can be mitigated by using technology to facilitate communication and improve follow-up care. The importance of training physicians to be good communicators is also stressed. New technology including automated telephone systems, texting and email will improve access to patients and hopefully encourage compliance and follow-up.

Progesterone treatment alters neurotrophin/proneurotrophin balance and receptor expression in rats with traumatic brain injury.

PURPOSE: The neuroactive steroid progesterone (PROG) has been shown to be an effective treatment for traumatic brain injury (TBI) both in animal models and in humans, but the signaling pathways involved have not yet been fully described. Here we characterize the protein expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and their pro-proteins and receptors following PROG treatment for TBI. METHODS: To evaluate whether PROG treatment given after TBI alters mature and proneurotrophin protein balance and the expression of receptors involved in apoptotic and cell survival signaling, we used Western blots in tissue obtained 24 h, 72 h, and 7 days after injury from rats with bilateral frontal cortical contusions. RESULTS: Compared to controls, PROG reduced levels of pro-apoptotic NGF precursor (proNGF) at 24 h and 7 days post-injury, reduced levels of pro-apoptotic BDNF precursor (proBDNF) and the BDNF receptor TrkB at all time points, and increased levels of mature NGF at 72 h. Levels of mature BDNF were decreased at 24 and 72 h. These observations were associated with reduced markers of apoptosis and improved behavioral parameters in PROG-treated rats. CONCLUSIONS: Some of PROG's protective effects after TBI are mediated, in part, by simultaneous induction of pro-survival neurotrophin signaling and inhibition of apoptotic proneurotrophin signaling.

Progesterone and vitamin d hormone as a biologic treatment of traumatic brain injury in the aged.

There is growing recognition that traumatic brain injury is a highly variable and complex systemic disorder that is refractory to therapies that target individual mechanisms. It is even more complex in elderly persons, in whom frailty, previous comorbidities, altered metabolism, and a long history of medication use are likely to complicate the secondary effects of brain trauma. Progesterone, one of the few neuroprotective agents that has shown promise for the treatment of acute brain injury, is now in national and international phase 3 multicenter trials. New findings show that vitamin D hormone (VDH) and VDH deficiency in the aging process (and across the developmental spectrum) may interact with progesterone and treatment for traumatic brain injury. In this article we review the use of progesterone and VDH as biologics-based therapies along with recent studies demonstrating that the combination of progesterone and VDH may promote better functional outcomes than either treatment independently.

Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats.

Administration of the neurosteroid progesterone (PROG) has been shown to be beneficial in a number of brain injury models and in two recent clinical trials. Given widespread vitamin D deficiency and increasing traumatic brain injuries (TBIs) in the elderly, we investigated the interaction of vitamin D deficiency and PROG with cortical contusion injury in aged rats. Vitamin D deficient (VitD-deficient) animals showed elevated inflammatory proteins (TNFα, IL-1ß, IL-6, NFκB p65) in the brain even without injury. VitD-deficient rats with TBI, whether given PROG or vehicle, showed increased inflammation and greater open-field behavioral deficits compared to VitD-normal animals. Although PROG was beneficial in injured VitD-normal animals, in VitD-deficient subjects neurosteroid treatment conferred no improvement over vehicle. A supplemental dose of 1,25-dihydroxyvitamin D(3) (VDH) given with the first PROG treatment dramatically improved results in VitD-deficient rats, but treatment with VDH alone did not. Our results suggest that VitD-deficiency can increase baseline brain inflammation, exacerbate the effects of TBI, and attenuate the benefits of PROG treatment; these effects may be reversed if the deficiency is corrected.

Traumatic brain injury and aging: is a combination of progesterone and vitamin D hormone a simple solution to a complex problem?

Although progress is being made in the development of new clinical treatments for traumatic brain injury (TBI), little is known about whether such treatments are effective in older patients, in whom frailty, prior medical conditions, altered metabolism, and changing sensitivity to medications all can affect outcomes following a brain injury. In this review we consider TBI to be a complex, highly variable, and systemic disorder that may require a new pharmacotherapeutic approach, one using combinations or cocktails of drugs to treat the many components of the injury cascade. We review some recent research on the role of vitamin D hormone and vitamin D deficiency in older subjects, and on the interactions of these factors with progesterone, the only treatment for TBI that has shown clinical effectiveness. Progesterone is now in phase III multicenter trial testing in the United States. We also discuss some of the potential mechanisms and pathways through which the combination of hormones may work, singly and in synergy, to enhance survival and recovery after TBI.

Combination treatment with progesterone and vitamin D hormone may be more effective than monotherapy for nervous system injury and disease.

More than two decades of pre-clinical research and two recent clinical trials have shown that progesterone (PROG) and its metabolites exert beneficial effects after traumatic brain injury (TBI) through a number of metabolic and physiological pathways that can reduce damage in many different tissues and organ systems. Emerging data on 1,25-dihydroxyvitamin D(3) (VDH), itself a steroid hormone, have begun to provide evidence that, like PROG, it too is neuroprotective, although some of its actions may involve different pathways. Both agents have high safety profiles, act on many different injury and pathological mechanisms, and are clinically relevant, easy to administer, and inexpensive. Furthermore, vitamin D deficiency is prevalent in a large segment of the population, especially the elderly and institutionalized, and can significantly affect recovery after CNS injury. The combination of PROG and VDH in pre-clinical and clinical studies is a novel and compelling approach to TBI treatment.

"Thinking about not-thinking": neural correlates of conceptual processing during Zen meditation.

Recent neuroimaging studies have identified a set of brain regions that are metabolically active during wakeful rest and consistently deactivate in a variety the performance of demanding tasks. This "default network" has been functionally linked to the stream of thoughts occurring automatically in the absence of goal-directed activity and which constitutes an aspect of mental behavior specifically addressed by many meditative practices. Zen meditation, in particular, is traditionally associated with a mental state of full awareness but reduced conceptual content, to be attained via a disciplined regulation of attention and bodily posture. Using fMRI and a simplified meditative condition interspersed with a lexical decision task, we investigated the neural correlates of conceptual processing during meditation in regular Zen practitioners and matched control subjects. While behavioral performance did not differ between groups, Zen practitioners displayed a reduced duration of the neural response linked to conceptual processing in regions of the default network, suggesting that meditative training may foster the ability to control the automatic cascade of semantic associations triggered by a stimulus and, by extension, to voluntarily regulate the flow of spontaneous mentation.

Progesterone and its metabolite allopregnanolone differentially regulate hemostatic proteins after traumatic brain injury.

Our laboratory has shown in numerous experiments that the neurosteroids progesterone (PROG) and allopregnanolone (ALLO) improve molecular and functional outcomes after traumatic brain injury (TBI). As coagulopathy is an important contributor to the secondary destruction of nervous tissue, we hypothesized that PROG and ALLO administration may also have a beneficial effect on coagulation protein expression after TBI. Adult male Sprague-Dawley rats were given bilateral contusions of the medial frontal cortex followed by treatments with PROG (16 mg/kg), ALLO (8 mg/kg), or vehicle (22.5% hydroxypropyl-beta-cyclodextrin). Controls received no injury or injections. Progesterone generally maintained procoagulant (thrombin, fibrinogen, and coagulation factor XIII), whereas ALLO increased anticoagulant protein expression (tissue-type plasminogen activator, tPA). In addition, PROG significantly increased the ratio of tPA bound to neuroserpin, a serine protease inhibitor that can reduce the activity of tPA. Our findings suggest that in a model of TBI, where blood loss may exacerbate injury, it may be preferable to treat patients with PROG, whereas it might be more appropriate to use ALLO as a treatment for thrombotic stroke, where a reduction in coagulation would be more beneficial.

Neurosteroids reduce inflammation after TBI through CD55 induction.

The inflammatory cascade that follows traumatic brain injury may lead to secondary cell death and can impede recovery of function. Complement factors and their convertases are increased in glia after brain injury and lead to the production of inflammatory products that kill vulnerable neurons. Progesterone and its metabolite allopregnanolone (5alpha-pregnan-3beta-ol-20-one) have been shown to reduce the expression of inflammatory cytokines in the acute stages of brain injury, although how they do this is not completely understood. In this study we show that both progesterone and allopregnanolone treatments enhance the production of CD55 following contusion injuries of the cerebral cortex in rats. CD55, a single-chain type 1 cell surface protein, is a potent inhibitor of the complement convertases which are activators of the inflammatory cascade. The increased expression of CD55 could be an important mechanism by which steroids help to reduce the cerebral damage caused by inflammation.

Progesterone improves acute recovery after traumatic brain injury in the aged rat.

Recent evidence has demonstrated that treatment with progesterone can attenuate many of the pathophysiological events following traumatic brain injury (TBI) in young adult rats, but this effect has not been investigated in aged animals. In this study, 20-month-old male Fischer 344 rats with bilateral contusions of the frontal cortex (n = 4 per group) or sham operations received 8, 16, or 32 mg/kg of progesterone or vehicle. Locomotor activity was measured at 72 h to assess behavioral recovery. Brain tissue was harvested at 24, 48, and 72 h, and Western blotting was performed for inflammatory and apoptotic factors. Edema was assessed at 48 h by measuring brain water content. Injured animals treated with 8 and 16 mg/kg progesterone showed decreased expression of COX-2, IL-6, and NFkappaB at all time points, indicating a reduction in the acute inflammatory process compared to vehicle. The 16 mg/kg group also showed reduced apoptosis at all time points as well as decreased edema and improved locomotor outcomes. Thus, in aged male rats, treatment with 16 mg/kg progesterone improves short-term motor recovery and attenuates edema, secondary inflammation, and cell death after TBI.

Age effects on gray matter volume and attentional performance in Zen meditation.

Zen meditation, a Buddhist practice centered on attentional and postural self-regulation, has been speculated to bring about beneficial long-term effects for the individual, ranging from stress reduction to improvement of cognitive function. In this study, we examined how the regular practice of meditation may affect the normal age-related decline of cerebral gray matter volume and attentional performance observed in healthy individuals. Voxel-based morphometry for MRI anatomical brain images and a computerized sustained attention task were employed in 13 regular practitioners of Zen meditation and 13 matched controls. While control subjects displayed the expected negative correlation of both gray matter volume and attentional performance with age, meditators did not show a significant correlation of either measure with age. The effect of meditation on gray matter volume was most prominent in the putamen, a structure strongly implicated in attentional processing. These findings suggest that the regular practice of meditation may have neuroprotective effects and reduce the cognitive decline associated with normal aging.

Neurobiological substrates of dread.

Given the choice of waiting for an adverse outcome or getting it over with quickly, many people choose the latter. Theoretical models of decision-making have assumed that this occurs because there is a cost to waiting-i.e., dread. Using functional magnetic resonance imaging, we measured the neural responses to waiting for a cutaneous electric shock. Some individuals dreaded the outcome so much that, when given a choice, they preferred to receive more voltage rather than wait. Even when no decision was required, these extreme dreaders were distinguishable from those who dreaded mildly by the rate of increase of neural activity in the posterior elements of the cortical pain matrix. This suggests that dread derives, in part, from the attention devoted to the expected physical response and not simply from fear or anxiety. Although these differences were observed during a passive waiting procedure, they correlated with individual behavior in a subsequent choice paradigm, providing evidence for a neurobiological link between the experienced disutility of dread and subsequent decisions about unpleasant outcomes.