Explore the vast range of titles available.

Magnetic resonance-guided focused ultrasound in combination with intravenously injected microbubbles has been shown to transiently open the blood–brain barrier, and reduce beta-amyloid and tau pathology in animal models of Alzheimer’s disease. Here, we used focused ultrasound to open the blood–brain barrier in five patients with early to moderate Alzheimer’s disease in a phase I safety trial. In all patients, the blood–brain barrier within the target volume was safely, reversibly, and repeatedly opened. Opening the blood–brain barrier did not result in serious clinical or radiographic adverse events, as well as no clinically significant worsening on cognitive scores at three months compared to baseline. Beta-amyloid levels were measured before treatment using [ 18 F]-florbetaben PET to confirm amyloid deposition at the target site. Exploratory analysis suggested no group-wise changes in amyloid post-sonication. The results of this safety and feasibility study support the continued investigation of focused ultrasound as a potential novel treatment and delivery strategy for patients with Alzheimer’s disease. Magnetic resonance-guided focused ultrasound with injected microbubbles has been used to temporarily open the blood–brain barrier (BBB) in animal models of Alzheimer's disease (AD). Here, the authors use this technology to non-invasively open the BBB in 5 patients with mild-to-moderate AD in a phase I trial, and show that the procedure is safe.

Magnetic resonance-guided focused ultrasound (MRgFUS), in conjunction with circulating microbubbles, is an emerging technology that can transiently enhance the permeability of the blood-brain barrier (BBB) locally and non-invasively to facilitate targeted drug delivery to the brain. In this clinical trial, the feasibility and safety of BBB modulation in the putamen were evaluated for biweekly therapeutic agent delivery in patients with Parkinson’s disease. The performance of the clinical MRgFUS system’s cavitation feedback controller for active power modulation throughout the exposures was examined. The putamen was targeted unilaterally by an ExAblate Neuro MRgFUS system operating at 220 kHz. Definity microbubbles were infused via a saline bag gravity drip at a rate of 4 µL/kg per 5 min. A cavitation emissions-based feedback controller was employed to modulate the acoustic power automatically according to prescribed target cavitation dose levels. BBB opening was measured by Gadolinium (Gd)-enhanced T1-weighted MR imaging, and the presence of potential micro-hemorrhages induced by the exposures was assessed via T2*-weighted MR imaging. A total of 12 treatment sessions were carried out across four patients, with target cavitation dose levels ranging from 0.20–0.40. BBB permeability in the targeted putamen was elevated successfully in all treatments, with a 14% ± 6% mean increase in Gd-enhanced T1-weighted MRI signal intensity relative to the untreated contralateral side. No indications of red blood cell extravasations were observed on MR imaging scans acquired one day following each treatment session. The cavitation emissions-based feedback controller was effective in modulating acoustic power levels to ensure BBB permeability enhancement while avoiding micro-hemorrhages, however, further technical advancements are warranted to improve its performance for use across a wide variety of brain diseases.

To measure how frequently somatosensory-evoked potentials (SEPs) are used in comatose patients after traumatic brain injury (TBI) and hypoxic ischemic encephalopathy (HIE), how SEPs contribute to outcome prediction and clinical decision making, and how available they are to clinicians. A novel factual and scenario-based survey instrument to measure patterns of SEPs use in comatose patients due to HIE or TBI was distributed to critical care, neurology, and neurosurgical physicians across Canada. The analysis was based on 86 completed surveys from specialists in neurology (36), neurosurgery (24), and critical care (22). Most (73%) of respondents reported that SEPs were available. When provided clinical vignettes, only 36% indicated that they would use them in TBI and 49% would use them in HIE. When respondents ranked the various methods available for establishing prognosis for awakening, SEP was ranked after cerebral blood flow and magnetic resonance imaging. The majority did not accurately estimate chances of awakening when SEP responses were bilaterally absent. There are significant opportunities to optimize the use of SEPs in comatose patients including standardizing SEP testing and reporting, better communicating results to critical care physicians, and improving the understanding regarding the recommended use and interpretation of these tests.

The blood-brain barrier (BBB) has long limited therapeutic access to brain tumor and peritumoral tissue. In animals, MR-guided focused ultrasound (MRgFUS) with intravenously injected microbubbles can temporarily and repeatedly disrupt the BBB in a targeted fashion, without open surgery. Our objective is to demonstrate safety and feasibility of MRgFUS BBB opening with systemically administered chemotherapy in patients with glioma in a phase I, single-arm, open-label study. Five patients with previously confirmed or suspected high-grade glioma based on imaging underwent the MRgFUS in conjunction with administration of chemotherapy (n = 1 liposomal doxorubicin, n = 4 temozolomide) one day prior to their scheduled surgical resection. Samples of “sonicated” and “unsonicated” tissue were measured for the chemotherapy by liquid-chromatography-mass spectrometry. Complete follow-up was three months. The procedure was well-tolerated, with no adverse clinical or radiologic events related to the procedure. The BBB within the target volume showed radiographic evidence of opening with an immediate 15–50% increased contrast enhancement on T1-weighted MRI, and resolution approximately 20 hours after. Biochemical analysis of sonicated versus unsonicated tissue suggest chemotherapy delivery is feasible. In this study, we demonstrated transient BBB opening in tumor and peritumor tissue using non-invasive low-intensity MRgFUS with systemically administered chemotherapy was safe and feasible. The characterization of therapeutic delivery and clinical response to this treatment paradigm requires further investigation.

MR-guided focused ultrasound (MRgFUS) can temporarily permeabilize the blood-brain barrier (BBB), noninvasively, to allow therapeutics access to the central nervous system. However, its secondary and potential neuromodulation effects are not well understood. We aimed to characterize the functional impact of MRgFUS BBB opening in human subjects, based on the phase I trial in patients with Alzheimer's disease. We analyzed for changes in bilateral frontoparietal networks in resting state functional MRI from five subjects after BBB opening in the right frontal lobe. We found a transient functional connectivity decrease within only the ipsilateral frontoparietal network that was recovered by the next day. Additionally, baseline to month three comparisons did not reveal any significant differences from matched-controls from the Alzheimer's Disease Neuroimaging Initiative. Overall, MRgFUS may transiently affect neurologic function, but the functional organization is restored at one day and remains unchanged at three months. This first in human data has implications for the development of MRgFUS as a drug delivery platform to pathologic brain tissue and potential use for non-invasive neuromodulation. •Focused ultrasound causes transient mechanical disruption of blood-brain barrier.•First-in-human data; ultrasound to prefrontal cortex decreases functional connectivity.•Reductions are isolated to ipsilateral frontoparietal network, recovered next day.•Ensuing functional organization unaffected at month 3 and compared to matched controls.•Implications for technology's safety and potential for non-invasive neuromodulation.

Patient recall of information about procedures, including risks and benefits and potential outcomes, is often insufficient. We sought to determine whether a multimedia educational tool enhances the informed consent discussion for elective neurosurgical procedures by increasing patient knowledge of the procedure. Adult patients from a single neurosurgical site eligible for 4 neurosurgical procedures (lumbar spine or cervical spine decompression for degenerative disease, craniotomy for brain tumour or trigeminal neuralgia treatment) were offered enrolment. Patients were randomly assigned to either the control arm (standard consent discussion) or the intervention arm (review of an e-book containing information tailored to their disease/injury plus standard consent discussion). Participants completed a 14-item questionnaire before and after the consent discussion. Questionnaires were completed by 38 participants, 18 in the control group and 20 in the intervention group. The mean age was 62.2 (standard deviation [SD] 13.6) years and did not differ significantly between the 2 groups. The mean baseline questionnaire scores were similar for the control and intervention groups (20.4 [SD 7.3] v. 20.6 [SD 6.7]). However, the mean scores on the follow-up questionnaire were significantly different between the 2 groups (20.2 [SD 4.0] v. 23.2 [SD 4.9], = 0.02). There was no change in the scores on the 2 questionnaires in the control group, whereas, in the intervention group, the mean score was significantly higher after the intervention ( = 0.03). The use of an electronic booklet appears to improve patients’ knowledge of their surgical procedure. The use of multimedia booklets in clinical practice could help standardize and optimize the consent process, ensuring that patients receive the relevant information to make a truly informed decision.

Patient recall of information about procedures, including risks and benefits and potential outcomes, is often insufficient. We sought to determine whether a multimedia educational tool enhances the informed consent discussion for elective neurosurgical procedures by increasing patient knowledge of the procedure. Adult patients from a single neurosurgical site eligible for 4 neurosurgical procedures (lumbar spine or cervical spine decompression for degenerative disease, craniotomy for brain tumour or trigeminal neuralgia treatment) were offered enrolment. Patients were randomly assigned to either the control arm (standard consent discussion) or the intervention arm (review of an e-book containing information tailored to their disease/injury plus standard consent discussion). Participants completed a 14-item questionnaire before and after the consent discussion. Questionnaires were completed by 38 participants, 18 in the control group and 20 in the intervention group. The mean age was 62.2 (standard deviation [SD] 13.6) years and did not differ significantly between the 2 groups. The mean baseline questionnaire scores were similar for the control and intervention groups (20.4 [SD 7.3] v. 20.6 [SD 6.7]). However, the mean scores on the follow-up questionnaire were significantly different between the 2 groups (20.2 [SD 4.0] v. 23.2 [SD 4.9], p = 0.02). There was no change in the scores on the 2 questionnaires in the control group, whereas, in the intervention group, the mean score was significantly higher after the intervention (p = 0.03). The use of an electronic booklet appears to improve patients’ knowledge of their surgical procedure. The use of multimedia booklets in clinical practice could help standardize and optimize the consent process, ensuring that patients receive the relevant information to make a truly informed decision. Ce que les patients retiennent au sujet de leurs interventions, incluant les risques, les avantages et les résultats potentiels sont souvent insuffisants. Nous avons voulu déterminer si un outil d’enseignement multimédia peut faciliter la discussion entourant le consentement éclairé en prévision d’interventions neurochirurgicales non urgentes, en renseignant davantage les patients au sujet de leurs interventions. On a invité les patients adultes d’un centre de neurochirurgie admissibles à 4 types de différents d’interventions neurochirurgicale (décompression de la colonne lombaire ou cervicale pour maladie dégénérative, craniotomie pour tumeur cérébrale ou traitement de la névralgie du trijumeau) à s’inscrire à l’étude. Les patients ont été assignés aléatoirement soit au groupe témoin (discussion standard sur le consentement), soit au groupe soumis à l’intervention (utilisation d’une publication électronique contenant de l’information adaptée à leur maladie/lésion en plus de la discussion standard sur le consentement). Les participants ont répondu à un questionnaire en 14 points avant et après la discussion sur le consentement. Trente-huit participants ont répondu au questionnaire, 18 dans le groupe témoin et 20 dans le groupe soumis à l’intervention. L’âge moyen était de 62,2 ans (écart-type [É.-T.] 13,6 ans) et n’était pas significativement différent entre les 2 groupes. Les scores moyens au questionnaire de départ étaient similaires pour les 2 groupes (20,4 [É.-T. 7,3] c. 20,6 [É.-T. 6,7]). Par contre, les scores moyens au questionnaire de suivi ont été significativement différents entre les 2 groupes (20,2 [É.-T. 4,0] c. 23,2 [É.-T. 4,9], p = 0,02). On n’a observé aucun changement des scores entre les 2 questionnaires du groupe témoin, tandis que dans le groupe soumis à l’intervention, le score moyen a été significativement plus élevé après l’intervention (p = 0,03). L’utilisation d’un document électronique semble améliorer les connaissances des patients au sujet de leurs interventions chirurgicales. L’utilisation de documents multimédias dans la pratique clinique pourrait aider à standardiser et optimiser le processus de consentement et faire en sorte que les patients reçoivent une information pertinente pour prendre une décision réellement éclairée.

Novel neurointerventions present innovative therapeutic approaches to a range of treatment-refractory disorders. We sought to characterize factors that inform and define translational readiness for first-in-human (FIH) neuromodulatory trials. We used a two-part methodology involving a scoping review of the biomedical literature on the readiness of FIH trials for both neurological and non-neurological applications, and semi-structured interviews with stakeholders about decision-making for neuromodulation using magnetic resonance-guided focused ultrasound as a case example. One hundred and thirty factors relevant to FIH readiness were identified in the scoping review. Trial design, adequacy of preclinical evidence, and risk were ubiquitous across biotechnologies. Target organ, target function, and inadequacy of animal models were dominant in the neurointervention literature. Interview results on the relative importance of these factors reveal divergent values, priorities, and understandings both between patients and clinicians and between patients affected by different conditions. Readiness of neurotechnology for FIH trials is defined by a multitude of interacting factors that pertain to clinical and nonclinical priorities, perceptions, and values.

The proportionally fewer female African American nursing faculty at predominately White institutions (PWIs) have frequently reported adverse employment conditions in academia. The faculty within nursing schools at PWIs does not reflect society’s diversity. The problem addressed through this study is the low number of female African American nursing faculty in PWIs. The purpose of this basic qualitative study was to examine the experiences of non-tenured female African American nursing faculty at PWIs. The conceptual framework that informed this study is Crenshaw’s intersectionality. The research question addressed the experiences of non-tenured female African American nursing faculty at PWIs. Six non-tenured female African American nursing faculty from PWIs across the United States participated in semi-structured interviews. The key findings revealed that institutional racism contributed to the lack of faculty wanting to attain tenure, a convoluted tenure process for those on the tenure track, and the interactions with White colleagues in faculty meetings created toxic work environments. Implications for positive social change include providing context for the experiences of non-tenured female African American nursing faculty at PWIs. Nursing academia at PWIs acknowledging that institutional racism affects female African American faculty and promoting sincere conversations surrounding diversity, equity, and inclusion may mitigate these factors. The end goals for these conversations are to create safe spaces for female African American nursing faculty, develop and implement actionable items for dismantling the institutional pillars that uphold racism, inequity, and the lack of diversity in nursing academia.

BackgroundAwareness to neurocognitive issues after mild traumatic brain injury (mTBI) is increasing, but currently no imaging markers are available for mTBI. Advanced structural imaging recently showed microstructural tissue changes and axonal injury, mild but likely sufficient to lead to functional deficits. Magnetoencephalography (MEG) has high temporal and spatial resolution, combining structural and electrophysiological information, and can be used to examine brain activation patterns of regions involved with specific tasks.Methods16 adults with mTBI and 16 matched controls were submitted to neuropsychological testing (Wechsler Abbreviated Scale of Intelligence (WASI); Conners; Alcohol Use Disorders Identification Test (AUDIT); Generalised Anxiety Disorder Seven-item Scale (GAD-7); Patient Health Questionnaire (PHQ-9); Symptom Checklist and Symptom Severity Score (SCAT2)) and MEG while tested for mental flexibility (Intra-Extra Dimensional set-shifting tasks). Three-dimensional maps were generated using synthetic aperture magnetometry beamforming analyses to identify differences in regional activation and activation times. Reaction times and accuracy between groups were compared using 2×2 mixed analysis of variance.FindingsWhile accuracy was similar, patients with mTBI reaction time was delayed and sequence of activation of brain regions disorganised, with involvement of extra regions such as the occipital lobes, not used by controls. Examination of activation time showed significant delays in the right insula and left posterior parietal cortex in patients with mTBI.ConclusionsPatients with mTBI showed significant delays in the activation of important areas involved in executive function. Also, more regions of the brain are involved in an apparent compensatory effort. Our study suggests that MEG can detect subtle neural changes associated with cognitive dysfunction and thus, may eventually be useful for capturing and tracking the onset and course of cognitive symptoms associated with mTBI.