Transcirculation Pipeline embolization device deployment: a rescue technique.

The Pipeline embolization device (PED) has become a very important tool in the treatment of nonruptured cerebral aneurysms. However, a patient's difficult anatomy or vascular stenosis may affect the device delivery. The purpose of this article was to describe an alternate technique for PED deployment when ipsilateral anatomy is not amenable for catheter navigation. A 44-year-old woman with a symptomatic 6-mm right superior hypophyseal artery aneurysm and a known history of right internal carotid artery dissection presented for PED treatment of her aneurysm. An angiogram showed persistence of the arterial dissection with luminal stenosis after 6 months of dual antiplatelet treatment. The contralateral internal carotid artery was catheterized and the PED was deployed via a transcirculation approach, using the anterior communicating artery. Transcirculation deployment of a PED is a viable option when ipsilateral anatomy is difficult or contraindicated for this treatment.

Tau imaging in neurodegenerative diseases.

Aggregated tau protein is a major neuropathological substrate central to the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration and chronic traumatic encephalopathy. In AD, it has been shown that the density of hyperphosphorylated tau tangles correlates closely with neuronal dysfunction and cell death, unlike ß-amyloid. Until now, diagnostic and pathologic information about tau deposition has only been available from invasive techniques such as brain biopsy or autopsy. The recent development of selective in-vivo tau PET imaging ligands including [(18)F]THK523, [(18)F]THK5117, [(18)F]THK5105 and [(18)F]THK5351, [(18)F]AV1451(T807) and [(11)C]PBB3 has provided information about the role of tau in the early phases of neurodegenerative diseases, and provided support for diagnosis, prognosis, and imaging biomarkers to track disease progression. Moreover, the spatial and longitudinal relationship of tau distribution compared with ß - amyloid and other pathologies in these diseases can be mapped. In this review, we discuss the role of aggregated tau in tauopathies, the challenges posed in developing selective tau ligands as biomarkers, the state of development in tau tracers, and the new clinical information that has been uncovered, as well as the opportunities for improving diagnosis and designing clinical trials in the future.

Cortical hypermetabolism in MCI subjects: a compensatory mechanism?

PURPOSE: Alzheimer's disease (AD) is associated with amyloid accumulation that takes place decades before symptoms appear. Cognitive impairment in AD is associated with reduced glucose metabolism. However, neuronal plasticity/compensatory mechanisms might come into play before the onset of dementia. The aim of this study was to determine whether there is evidence of cortical hypermetabolism as a compensatory mechanism before amyloid deposition takes place in subjects with amnestic mild cognitive impairment (aMCI). METHODS: Nine AD subjects and ten aMCI subjects had both [(11)C]PIB and [(18)F]FDG PET scans with arterial input in order to quantify the amyloid deposition and glucose metabolism in vivo in comparison with healthy control subjects who underwent either [(11)C]PIB or [(18)F]FDG PET scans. The [(11)C]PIB PET scans were quantified using [(11)C]PIB target region to cerebellum uptake ratio images created by integrating the activity collected from 60 to 90 min, and regional cerebral glucose metabolism was quantified using spectral analysis. RESULTS: In MCI subjects, cortical hypermetabolism was observed in four amyloid-negative subjects and one amyloid-positive subject, while hypometabolism was seen in five other MCI subjects with high amyloid load. Subjects with hypermetabolism and low amyloid did not convert to AD during clinical follow-up for 18 months in contrast to four amyloid-positive hypometabolic subjects who did convert to AD. CONCLUSION: This preliminary study suggests that compensatory hypermetabolism can occur in aMCI subjects, particularly in those who are amyloid-negative. The increase in metabolic rate in different cortical regions with predominance in the occipital cortex may be a compensatory response to the neuronal damage occurring early in the disease process. It may also reflect recruitment of relatively minimally affected cortical regions to compensate for reduced function in the temporoparietal cortical association areas.

Synthetic organotelluride compounds induce the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisiae.

BACKGROUND: Resistance to fluconazole, a commonly used azole antifungal, is a challenge for the treatment of fungal infections. Resistance can be mediated by overexpression of ABC transporters, which promote drug efflux that requires ATP hydrolysis. The Pdr5p ABC transporter of Saccharomyces cerevisiae is a well-known model used to study this mechanism of antifungal resistance. The present study investigated the effects of 13 synthetic compounds on Pdr5p. RESULTS: Among the tested compounds, four contained a tellurium-butane group and shared structural similarities that were absent in the other tested compounds: a lateral hydrocarbon chain and an amide group. These four compounds were capable of inhibiting Pdr5p ATPase activity by more than 90%, they demonstrated IC50 values less than 2 µM and had an uncompetitive pattern of Pdr5p ATPase activity inhibition. These organotellurides did not demonstrate cytotoxicity against human erythrocytes or S. cerevisiae mutant strains (a strain that overexpress Pdr5p and a null mutant strain) even in concentrations above 100 µM. When tested at 100 µM, they could reverse the fluconazole resistance expressed by both the S. cerevisiae mutant strain that overexpress Pdr5p and a clinical isolate of Candida albicans. CONCLUSIONS: We have identified four organotellurides that are promising candidates for the reversal of drug resistance mediated by drug efflux pumps. These molecules will act as scaffolds for the development of more efficient and effective efflux pump inhibitors that can be used in combination therapy with available antifungals.

Diagnosis and treatment of arterial dissections.

Dissections of the cervical and intracranial vessels represent an important source of stroke in those less than 50 years of age. This can occur spontaneously or following trauma, minor or major. Rapid diagnosis is essential to limit subsequent sequelae and modern computed tomographic angiography represents an appropriately sensitive modality. Treatment must be individualized to the patient and can consist of an antiplatelet regimen, anticoagulation, or endovascular intervention. No evidence demonstrates superiority of either medical modality and even aspirin alone may be efficacious. Consideration should be given to this in the multi-trauma population in which more aggressive anticoagulation is contraindicated. In addition, thrombolytic administration should not be withheld would it otherwise be indicated. Endovascular intervention is reserved for those with hemodynamically significant narrowing, enlarging pseudoaneurysms, fistulas formation, or subarachnoid hemorrhage.

Evaluation of two quantitative analysis methods of optical coherence tomography for detection of enamel demineralization and comparison with microhardness.

BACKGROUND AND OBJECTIVE: We aimed to evaluate in the same study two quantitative methods for quantification of incipient caries in human dental enamel by using optical coherence tomography (OCT): the optical attenuation coefficient and the area under the A-scan signal, and to compare their results with those obtained from microhardness analysis. STUDY DESIGN/MATERIALS AND METHODS: One hundred and sixty samples were obtained from 40 sound human third molars, which had their crowns sectioned. Simulated caries were created by a pH cycling method. OCT measurements were performed on the samples, before and after the induced demineralization. We determined the total optical attenuation coefficient from the OCT signal in each site and evaluated the sensitivity and specificity of this approach to the detection of the demineralization. Also, the areas under the OCT curves (AUC-OCT) and those from sectional microhardness tests (AUC-MH) were compared. RESULTS: Both the analysis of the optical attenuation coefficient and the AUC-OCT were adequate to efficiently distinguish sound and demineralized samples with sensitivity of 0.93 and specificity of 0.96. The AUC-MH and the AUC-OCT data presented linear relationship and correlation of 0.99. CONCLUSION: Both methods for signal analysis from OCT allowed detection of demineralization with good performance. The AUC-OCT approach enables obtaining a linear relation with the microhardness results, for a quantitative assessment of mineral loss in human teeth.

Batch and Continuous Flow Total Synthesis of Cannabidiol.

Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the synthesis of olivetolic acid derivatives and utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring (R)-(+)-limonene by photocatalysis. Key reactions, including the synthesis of olivetolic ester and a Friedel-Crafts alkylation, are successfully adapted to continuous flow, resulting in improved yields and selectivities. This study not only offers a scalable and efficient route for cannabidiol synthesis but also contributes to the synthetic approaches to access cannabinoids (diversity synthesis), with potential applications in medicinal and industrial contexts.

Comparison of MRI based and PET template based approaches in the quantitative analysis of amyloid imaging with PIB-PET.

RATIONALE: [(11)C]Pittsburgh compound-B (PIB) has been the most widely used positron emission tomography (PET) imaging agent for brain amyloid. Several longitudinal studies evaluating the progression of Alzheimer's disease (AD), and numerous therapeutic intervention studies are underway using [(11)C]PIB PET as an AD biomarker. Quantitative analysis of [(11)C]PIB data requires the definition of regional volumes of interest. This investigation systematically compared two data analysis routes both using a probabilistic brain atlas with 11 bilateral regions. Route 1 used individually segmented structural magnetic resonance images (MRI) for each subject while Route 2 used a standardised [(11)C]PIB PET template. METHODS: A total of 54 subjects, 20 with probable Alzheimer's disease (AD), 14 with amnestic Mild Cognitive Impairment (MCI) and 20 age-matched healthy controls, were scanned at two imaging centres either in London (UK) or in Turku (Finland). For all subjects structural volumetric MRI and [(11)C]PIB PET scans were acquired. Target-to-cerebellum ratios 40 min to 60 min post injection were used as outcome measures. Regional read outs for grey matter target regions were generated for both routes. Based on a composite neocortical, frontal, posterior cingulate, combined posterior cingulate and frontal cortical regions, scans were categorised into either 'PIB negative' (PIB-) or 'PIB positive' (PIB+) using previously reported cut-off target-to-cerebellar ratios of 1.41, 1.5 and 1.6, respectively. RESULTS: Target-to-cerebellum ratios were greater when defined with a [(11)C]PIB PET template than with individual MRIs for all cortical regions regardless of diagnosis. This difference was highly significant for controls (p<0.001, paired samples t-test), less significant for MCIs and borderline for ADs. Assignment of subjects to raised or normal categories was the same with both routes with a 1.6 cut-off while with lower cut off using frontal cortex, and combined frontal cortex and posterior cingulate demonstrated similar results, while posterior cingulate alone demonstrated significantly higher proportion of controls as amyloid positive by Route 2. CONCLUSIONS: Definition of cortical grey matter regions is more accurate when individually segmented MRIs (Route 1) were used rather than a population-based PET template (Route 2). The impact of this difference depends on the grey-to-white matter contrast in the PET images; specifically seen in healthy controls with high white matter and low grey matter uptake. When classifying AD, MCI and control subjects as normal or abnormal using large cortical regions; discordance was found between the MRI and template approach for those few subjects who presented with cortex-to-cerebellum ratios very close to the pre-assigned cut-off. However, posterior cingulate alone demonstrated significant discordance in healthy controls using template based approach. This study, therefore, demonstrates that the use of a [(11)C]PIB PET template (Route 2) is adequate for clinical diagnostic purposes, while MRI based analysis (Route 1) remains more appropriate for clinical research.

A Transcriptomic Comparative Study of Cranial Vasculature.

In genetic studies of cerebrovascular diseases, the optimal vessels to use as controls remain unclear. Our goal is to compare the transcriptomic profiles among 3 different types of control vessels: superficial temporal artery (STA), middle cerebral arteries (MCA), and arteries from the circle of Willis obtained from autopsies (AU). We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed upregulation of genes associated with tRNA/rRNA processing. Moreover, our results suggest that the matched case-control study design, which involves control STA samples collected from the same subjects of matched aneurysm samples in our study, can improve the identification of non-inherited disease-associated genes. Given the challenges associated with obtaining fresh intracranial arteries from healthy individuals, our study suggests that using MCA, AU, or paired STA samples as controls are feasible strategies for future large-scale studies investigating cerebral vasculopathies. However, the intrinsic differences of each type of control should be taken into consideration when interpreting the results. With the limitations of each control type, it may be most optimal to use multiple tissues as controls.

Can target-to-pons ratio be used as a reliable method for the analysis of [11C]PIB brain scans?

RATIONALE: (11)C]PIB is the most widely used PET imaging marker for amyloid in dementia studies. In the majority of studies the cerebellum has been used as a reference region. However, cerebellar amyloid may be present in genetic Alzheimer's (AD), cerebral amyloid angiopathy and prion diseases. Therefore, we investigated whether the pons could be used as an alternative reference region for the analysis of [(11)C]PIB binding in AD. The aims of the study were to: 1) Evaluate the pons as a reference region using arterial plasma input function and Logan graphical analysis of binding. 2) Assess the power of target-to-pons ratios to discriminate controls from AD subjects. 3) Determine the test-retest reliability in AD subjects. 4) Demonstrate the application of target-to-pons ratio in subjects with elevated cerebellar [(11)C]PIB binding. METHODS: 12 sporadic AD subjects aged 65 ± 4.5 yrs with a mean MMSE 21.4 ± 4 and 10 age-matched control subjects had [(11)C]PIB PET with arterial blood sampling. Three additional subjects (two subjects with pre-symptomatic presenilin-1 mutation carriers and one probable familial AD) were also studied. Object maps were created by segmenting individual MRIs and spatially transforming the gray matter images into standard stereotaxic MNI space and then superimposing a probabilistic atlas. Cortical [(11)C]PIB binding was assessed with an ROI (region of interest) analysis. Parametric maps of the volume of distribution (V(T)) were generated with Logan analysis. Additionally, parametric maps of the 60-90 min target-to-cerebellar ratio (RATIO(CER)) and the 60-90 min target-to-pons ratio (RATIO(PONS)) were computed. RESULTS: All three approaches were able to differentiate AD from controls (p<0.0001, nonparametric Wilcoxon rank sum test) in the target regions with RATIO(CER) and RATIO(PONS) differences higher than V(T) with use of an arterial input function. All methods had a good reproducibility (intraclass correlation coefficient>0.83); RATIO(CER) performed best closely followed by RATIO(PONS). The two subjects with presenilin-1 mutations and the probable familial AD case showed no significant differences in cortical binding using RATIO(CER), but the RATIO(PONS) approach revealed higher [(11)C]PIB binding in cortex and cerebellum. CONCLUSION: This study established 60-90 min target-to-pons RATIOs as a reliable method of analysis in [(11)C]PIB PET studies where cerebellum is not an appropriate reference region.

Somatic Variants in SVIL in Cerebral Aneurysms.

Background and Objectives: While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms. Methods: We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results. Results: Somatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway. Discussion: We propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.

Chronic hypoxia upregulates adenosine 2a receptor expression in chromaffin cells via hypoxia inducible factor-2α: role in modulating secretion.

Catecholamine (CAT) release from chromaffin tissue plays an essential role in the fetus which develops in a low O2 environment (hypoxia). To address molecular mechanisms regulating CAT secretion in low O2, we exposed a fetal chromaffin-derived cell line (MAH cells) to chronic hypoxia (CHox; 2% O2, 24h) and assessed gene expression using microarrays, quantitative RT-PCR, and western blot. CHox caused a dramatic ∼12× upregulation of adenosine A2a receptor (A2aR) mRNA, an effect critically dependent upon hypoxia-inducible factor (HIF)-2α which bound the promoter of the A2aR gene. In amperometric studies, acute hypoxia and high K⁺ (30 mM) evoked quantal CAT secretion that was enhanced after CHox, and further potentiated during simultaneous A2aR activation by adenosine. A2aR activation also enhanced stimulus-induced rise in intracellular Ca²âº in control, but not HIF-2α-deficient, MAH cells. Thus, A2aR, adenosine, and HIF-2α are key contributors to the potentiation of CAT secretion in developing chromaffin cells during chronic hypoxia.

Quantitative assessment of postural alignment in young adults based on photographs of anterior, posterior, and lateral views.

OBJECTIVE: Postural assessment through photography is a simple method that allows the acquisition of quantitative values to define the alignment of body segments. The purpose of this study was to quantitatively assess the postural alignment of several body segments in standing through anterior, posterior, and lateral views. METHODS: In this cross-sectional study, 122 subjects were initially evaluated. Seven subjects were excluded from the study after cluster analysis. The final sample had 115 subjects, 75% women with a mean age of 26 ± 7 years. Photographs were taken from anterior, posterior, and lateral views after placement of markers on specific anatomical points. Photographs were analyzed using free Postural Analysis Software/Software of Postural Analysis (PAS/SAPO). Quantitative values for postural analysis variables were ascertained for head, upper and lower limbs, and trunk, along with the frequency of inclinations to the left and to the right. RESULTS: Regarding the head, 88% of the sample presented some inclination, 67% of which was to the right. There was a predominance of right inclination of the shoulder and pelvis in 68% and 43% of study subjects, respectively. Lower limbs presented mean alignment of 178° in the anterior view, and the trunk showed predominant right inclination in 66% of participants. CONCLUSION: Small asymmetries were observed in anterior and posterior views. This study suggests that there is no symmetry in postural alignment and that small asymmetries represent the normative standard for posture in standing.

Deep brain stimulation of the orbitofrontal projections for the treatment of intermittent explosive disorder.

Intermittent explosive disorder (IED) is characterized by a dysfunction in the greater limbic system leading an individual to experience sudden aggressive behavior with little or no environmental perturbation. This report describes a procedure for the treatment of IED in a 19-year-old woman with a history of IED, having had episodes of severe violent attacks against family, dating to early childhood. Due to the severity and intractability of the illness, deep brain stimulation was performed, targeting the orbitofrontal projections to the hypothalamus. The patient's history and the procedure, management, and rationale are described in detail.

2-Cyclo-hexyl-4-methyl-tetra-hydro-pyran-4-ol.

In the title compound, C(12)H(22)O(2), the 4-methyl-tetra-hydro-pyran-4-ol ring adopts a conformation close to that of a chair and with the two O atoms syn; the cyclo-hexyl group occupies an equatorial position and adopts a chair conformation. In the crystal packing, supra-molecular chains along the b axis are sustained by O-H⋯O hydrogen bonds. These are connected into undulating layers in the ab plane by C-H⋯O inter-actions.

Early entrapment of fourth ventricle following Pseudomonas meningitis in extreme prematurity: Case report.

Trapped fourth ventricle (TFV) as a complication of post-hemorrhagic hydrocephalus (PHH) is widely reported in the pediatric population with a prior history of ventriculo-peritoneal (VP) shunt placement. Characterized by disproportionate dilatation of the fourth ventricle on serial neuro-imaging, it is rarely encountered in the early course of preterm infants and the differentiating clinical features are subtle and non-specific. Clinical alertness and sonographic correlation hold the key to early diagnosis. We report an early emergence of TFV in an extremely low gestational age newborn (ELGAN) following fulminant Pseudomonas aeruginosa meningitis, approach to management, and the neurological outcome. Fourth ventricle entrapment as a complication of perinatally acquired Pseudomonas aeruginosa meningitis in a surviving ELGAN is extremely rare.

Diffusion Tensor Imaging and Tractography Utilized in the Resection of a Midbrain Cavernous Malformation.

Background: Diffusion tensor imaging (DTI) is a magnetic resonance-based imaging technique that can provide important information about the underlying structure and integrity of the white matter in the brain. Tractography, a DTI postprocessing technique, can provide a detailed model of individual white matter fiber tracts. Knowledge of these tracts may be beneficial in the surgical planning and execution for neurosurgical patients. Case Report: We review the basic principles behind DTI and present an illustrative case in which DTI was used to delineate the relationship of eloquent white matter tracts to a cavernous malformation in a patient undergoing resection. Conclusion: The use of DTI during preoperative planning allows the neurosurgeon to understand if a lesion is disrupting, infiltrating, or altering the course of local white matter tracts. With the combined use of DTI and intraoperative neuronavigation, the neurosurgeon can better identify and avoid white matter tracts, not only in the local area of resection but also during approach to the lesion, thereby reducing the risk of damage to vital cortical pathways and subsequent functional impairment.

Interhemispheric Paracallosal Approach for an Arteriovenous Malformation of the Atrium: A Novel Technique.

Background: Intraventricular lesions present a surgical challenge because of the complexity of the ventricular anatomy, various perforating arteries, and eloquent brain areas surrounding the system. The ventricular atrium is particularly challenging because of the cingulate gyrus, corpus callosum, optic pathways, and significant vascular structures. We present the case of a patient for whom we used a new surgical approach to reach a lesion in the ventricular atrium. Case Report: A 26-year-old male presented with an intraventricular hemorrhage, acute hydrocephalus, and a grade III arteriovenous malformation (AVM) in the atrium of the left lateral ventricle. We approached the AVM through a posterior parietooccipital paracallosal interhemispheric approach. Instead of transecting the cingulate cortex as is traditionally done, we gently retracted the cingulate gyrus and made a small paracallosal incision to reach the atrium of the left lateral ventricle. The surgery was uneventful. The patient recovered well and was discharged home on postoperative day 3 without any deficits. Conclusion: This case illustrates a novel variation to an established approach to the ventricular atrium. With this technique, the surgeon minimizes disruption of brain tissue and thereby avoids the associated postoperative deficits associated with traditional approaches (transcortical, transcingulate, and conventional transcallosal). Tractography studies and a large cohort of patients are necessary to ensure the reproduction of good outcomes.

Carotid Web Stenting.

Background: Carotid webs are luminal, shelf-like protrusions at the carotid bulb. Considered to be a variant of fibromuscular dysplasia, carotid webs have been observed principally in African American females. The association between carotid webs and recurrent ischemic strokes continues to be established as patients without traditional stroke risk factors are found to have carotid webs as the only possible cause of symptomatic deficits. The majority of patients undergo endarterectomy; few stent placements are reported. We present the case of an African American female who underwent stent placement for treatment and secondary prevention of stroke attributed to a carotid web. Case Report: A 33-year-old African American female presented with acute onset left hemiparesis and left facial droop. Alteplase was administered; multiphase head and neck computed tomography angiography revealed an occlusion of the right middle cerebral artery with a web at the carotid bulb. Aspiration catheter thrombectomy achieved a Thrombolysis in Cerebral Infarction (TICI) score of 3. She was placed on 2 antiplatelet agents, and 3 weeks later she underwent stent placement. Follow-up digital subtraction angiography at 3 months showed obliteration of the right carotid artery web and satisfactory integration of the stent into the vessel wall. She was reassessed at 1 year and reported no neurologic symptoms. Conclusion: Although carotid webs are most commonly treated with endarterectomy, they may be amenable to stent therapy with favorable clinical outcomes as shown with this patient.

Commentary: The Tulane University-Ochsner Clinic Foundation Neurosurgery Program: 75 Years of History, Including the Program's Rebirth After Katrina.

Neurosurgery training in New Orleans began when Dr Dean Echols became the head of Neurosurgery for the Ochnser Clinic and Charity Hospital in 1944. The oldest in Louisiana, the Tulane-Ochsner program has trained 63 board-certified neurosurgeons since its founding, including 5 chairmen. The program has a colorful history linked to New Orleans. Its residents have enjoyed training at Charity Hospital, Tulane Hospital and Clinics, Veterans Affairs Medical Center, and the Ochsner Clinic Foundation.