A look into stent-related thrombus-burden: Bivalirudin versus heparin.

Use of optical coherence tomography (OCT) adds an assessment of thrombus burden remaining on stents after PCI for acute coronary syndromes. Potential variations in stent-related thrombus burden can be documented by OCT as a function of peri-procedural pharmacology supporting the use of OCT in future hypothesis testing. Bivalirudin remains a reliable and expensive alternative to heparin in cases of HIT or patients at high bleeding risk during transfemoral PCI.

Symmetrical Peripheral Gangrene Associated with Low Output Cardiac Failure.

Symmetrical peripheral gangrene (SPG) is a rare entity characterized by ischemic changes of the distal extremities with maintained vascular integrity. We present the case of a 64-year-old man with bilateral necrotic toes and deranged liver function tests. This was thought to be related to severely depressed ejection fraction from non-ischemic etiology, presumably chronic alcohol ingestion. We hope that awareness of SPG and association with a low output state will aid in early detection and prevention.

Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity.

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain's connectivity pattern, allowing us to discover genetic variants that affect the human brain's wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer's disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.

Abnormal hippocampal morphology in dissociative identity disorder and post-traumatic stress disorder correlates with childhood trauma and dissociative symptoms.

Smaller hippocampal volume has been reported in individuals with post-traumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization are still unclear. Brain structural magnetic resonance imaging scans were analyzed for 33 outpatients (17 with DID and 16 with PTSD only) and 28 healthy controls (HC), all matched for age, sex, and education. DID patients met criteria for PTSD (PTSD-DID). Hippocampal global and subfield volumes and shape measurements were extracted. We found that global hippocampal volume was significantly smaller in all 33 patients (left: 6.75%; right: 8.33%) compared with HC. PTSD-DID (left: 10.19%; right: 11.37%) and PTSD-only with a history of childhood traumatization (left: 7.11%; right: 7.31%) had significantly smaller global hippocampal volume relative to HC. PTSD-DID had abnormal shape and significantly smaller volume in the CA2-3, CA4-DG and (pre)subiculum compared with HC. In the patient groups, smaller global and subfield hippocampal volumes significantly correlated with higher severity of childhood traumatization and dissociative symptoms. These findings support a childhood trauma-related etiology for abnormal hippocampal morphology in both PTSD and DID and can further the understanding of neurobiological mechanisms involved in these disorders.

Neuroimaging, nutrition, and iron-related genes.

Several dietary factors and their genetic modifiers play a role in neurological disease and affect the human brain. The structural and functional integrity of the living brain can be assessed using neuroimaging, enabling large-scale epidemiological studies to identify factors that help or harm the brain. Iron is one nutritional factor that comes entirely from our diet, and its storage and transport in the body are under strong genetic control. In this review, we discuss how neuroimaging can help to identify associations between brain integrity, genetic variations, and dietary factors such as iron. We also review iron's essential role in cognition, and we note some challenges and confounds involved in interpreting links between diet and brain health. Finally, we outline some recent discoveries regarding the genetics of iron and its effects on the brain, suggesting the promise of neuroimaging in revealing how dietary factors affect the brain.

Advances in Neuro-Oncological Imaging: An Update on Diagnostic Approach to Brain Tumors.

This study delineates the pivotal role of imaging within the field of neurology, emphasizing its significance in the diagnosis, prognostication, and evaluation of treatment responses for central nervous system (CNS) tumors. A comprehensive understanding of both the capabilities and limitations inherent in emerging imaging technologies is imperative for delivering a heightened level of personalized care to individuals with neuro-oncological conditions. Ongoing research in neuro-oncological imaging endeavors to rectify some limitations of radiological modalities, aiming to augment accuracy and efficacy in the management of brain tumors. This review is dedicated to the comparison and critical examination of the latest advancements in diverse imaging modalities employed in neuro-oncology. The objective is to investigate their respective impacts on diagnosis, cancer staging, prognosis, and post-treatment monitoring. By providing a comprehensive analysis of these modalities, this review aims to contribute to the collective knowledge in the field, fostering an informed approach to neuro-oncological care. In conclusion, the outlook for neuro-oncological imaging appears promising, and sustained exploration in this domain is anticipated to yield further breakthroughs, ultimately enhancing outcomes for individuals grappling with CNS tumors.

Brain Cell-based Genetic Subtyping and Drug Repositioning for Alzheimer Disease.

Alzheimer's Disease (AD) is characterized by its complex and heterogeneous etiology and gradual progression, leading to high drug failure rates in late-stage clinical trials. In order to better stratify individuals at risk for AD and discern potential therapeutic targets we employed a novel procedure utilizing cell-based co-regulated gene networks and polygenic risk scores (cbPRSs). After defining genetic subtypes using extremes of cbPRS distributions, we evaluated correlations of the genetic subtypes with previously defined AD subtypes defined on the basis of domain-specific cognitive functioning and neuroimaging biomarkers. Employing a PageRank algorithm, we identified priority gene targets for the genetic subtypes. Pathway analysis of priority genes demonstrated associations with neurodegeneration and suggested candidate drugs currently utilized in diabetes, hypertension, and epilepsy for repositioning in AD. Experimental validation utilizing human induced pluripotent stem cell (hiPSC)-derived astrocytes demonstrated the modifying effects of estradiol, levetiracetam, and pioglitazone on expression of APOE and complement C4 genes, suggesting potential repositioning for AD.

Maximizing power to track Alzheimer's disease and MCI progression by LDA-based weighting of longitudinal ventricular surface features.

We propose a new method to maximize biomarker efficiency for detecting anatomical change over time in serial MRI. Drug trials using neuroimaging become prohibitively costly if vast numbers of subjects must be assessed, so it is vital to develop efficient measures of brain change. A popular measure of efficiency is the minimal sample size (n80) needed to detect 25% change in a biomarker, with 95% confidence and 80% power. For multivariate measures of brain change, we can directly optimize n80 based on a Linear Discriminant Analysis (LDA). Here we use a supervised learning framework to optimize n80, offering two alternative solutions. With a new medial surface modeling method, we track 3D dynamic changes in the lateral ventricles in 2065 ADNI scans. We apply our LDA-based weighting to the results. Our best average n80-in two-fold nested cross-validation-is 104 MCI subjects (95% CI: [94,139]) for a 1-year drug trial, and 75AD subjects [64,102]. This compares favorably with other MRI analysis methods. The standard "statistical ROI" approach applied to the same ventricular surfaces requires 165 MCI or 94AD subjects. At 2 years, the best LDA measure needs only 67 MCI and 52AD subjects, versus 119 MCI and 80AD subjects for the stat-ROI method. Our surface-based measures are unbiased: they give no artifactual additive atrophy over three time points. Our results suggest that statistical weighting may boost efficiency of drug trials that use brain maps.

Unbiased tensor-based morphometry: improved robustness and sample size estimates for Alzheimer's disease clinical trials.

Various neuroimaging measures are being evaluated for tracking Alzheimer's disease (AD) progression in therapeutic trials, including measures of structural brain change based on repeated scanning of patients with magnetic resonance imaging (MRI). Methods to compute brain change must be robust to scan quality. Biases may arise if any scans are thrown out, as this can lead to the true changes being overestimated or underestimated. Here we analyzed the full MRI dataset from the first phase of Alzheimer's Disease Neuroimaging Initiative (ADNI-1) from the first phase of Alzheimer's Disease Neuroimaging Initiative (ADNI-1) and assessed several sources of bias that can arise when tracking brain changes with structural brain imaging methods, as part of a pipeline for tensor-based morphometry (TBM). In all healthy subjects who completed MRI scanning at screening, 6, 12, and 24months, brain atrophy was essentially linear with no detectable bias in longitudinal measures. In power analyses for clinical trials based on these change measures, only 39AD patients and 95 mild cognitive impairment (MCI) subjects were needed for a 24-month trial to detect a 25% reduction in the average rate of change using a two-sided test (α=0.05, power=80%). Further sample size reductions were achieved by stratifying the data into Apolipoprotein E (ApoE) ε4 carriers versus non-carriers. We show how selective data exclusion affects sample size estimates, motivating an objective comparison of different analysis techniques based on statistical power and robustness. TBM is an unbiased, robust, high-throughput imaging surrogate marker for large, multi-site neuroimaging studies and clinical trials of AD and MCI.

Hippocampal structure and human cognition: key role of spatial processing and evidence supporting the efficiency hypothesis in females.

Here we apply a method for automated segmentation of the hippocampus in 3D high-resolution structural brain MRI scans. One hundred and four healthy young adults completed twenty one tasks measuring abstract, verbal, and spatial intelligence, along with working memory, executive control, attention, and processing speed. After permutation tests corrected for multiple comparisons across vertices (p < .05) significant relationships were found for spatial intelligence, spatial working memory, and spatial executive control. Interactions with sex revealed significant relationships with the general factor of intelligence (g), along with abstract and spatial intelligence. These correlations were mainly positive for males but negative for females, which might support the efficiency hypothesis in women. Verbal intelligence, attention, and processing speed were not related to hippocampal structural differences.

Comparison of Lumbosacral Fusion Grade in Patients after Transforaminal and Anterior Lumbar Interbody Fusion with Minimum 2-Year Follow-Up.

OBJECTIVE: Generally, anterior lumbar interbody fusion (ALIF) was believed superior to transforaminal lumbar interbody fusion (TLIF) in induction of fusion. However, many studies have reported comparable results in lumbosacral fusion rate between the two approaches. This study aimed to evaluate the realistic lumbosacral arthrodesis rates following ALIF and TLIF in patients with degenerative spondylolisthesis as measured by CT and radiology. METHODS: Ninety-six patients who underwent single-level L5-S1 fusion through ALIF (n = 48) or TLIF (n = 48) for degenerative spondylolisthesis at the Spine Center, University of California San Francisco, between October 2014 and December 2017 were retrospectively evaluated. Fusion was independently evaluated and categorized as solid fusion, indeterminate fusion, or pseudarthroses by two radiologists using the modified Brantigan-Steffee-Fraser (mBSF) grade. Clinical data on sex, age, body mass index, Meyerding grade, smoking status, follow-up times, complications, and radiological parameters including disc height, disc angle, segmental lordosis, and overall lumbar lordosis were collected. The fusion results and clinical and radiographic data were statistically compared between the ALIF and TLIF groups by using t-test or chi-square test. RESULTS: The mean follow-up period was 37.5 (ranging from 24 to 51) months. Clear, solid radiographic fusions were higher in the ALIF group compared with the TLIF group at the last follow-up (75% vs 47.9%, p = 0.006). Indeterminate fusion occurred in 20.8% (10/48) of ALIF cases and in 43.8% (21/48) of TLIF cases (p = 0.028). Radiographic pseudarthrosis was not significantly different between the TLIF and ALIF groups (16.7% vs 8.3%; p = 0.677). In subgroup analysis of the patients without bone morphogenetic protein (BMP), the solid radiographic fusion rate was significantly higher in the ALIF group than that in the TLIF group (78.6% vs 45.5%; p = 0.037). There were no differences in sex, age, body mass index, Meyerding grade, smoking status, or follow-up time between the two groups (p > 0.05). The ALIF group had more improvement in disc height (7.8 mm vs 4.7 mm), disc angle (5.2° vs 1.5°), segmental lordosis (7.0° vs 2.5°), and overall lumbar lordosis (4.7° vs 0.7°) compared with the TLIF group (p < 0.05). Overall complication rates were similar between the TLIF and ALIF groups (10.4% vs 8.33%; p > 0.999). CONCLUSIONS: With a minimum 2-year radiographic analysis of arthrodesis at lumbosacral level by radiologists, the rate of solid radiographic fusions was higher in the ALIF group compared with the TLIF group, whereas the TLIF group had a higher rate of indeterminate fusion. Radiographic pseudarthrosis did not differ significantly between the TLIF and ALIF groups.

Differential putaminal morphology in Huntington's disease, frontotemporal dementia and Alzheimer's disease.

OBJECTIVE: Direct neuronal loss or deafferentation of the putamen, a critical hub in corticostriatal circuits, may result in diverse and distinct cognitive and motoric dysfunction in neurodegenerative disease. Differential putaminal morphology, as a quantitative measure of corticostriatal integrity, may thus be evident in Huntington's disease (HD), Alzheimer's disease (AD) and frontotemporal dementia (FTD), diseases with differential clinical dysfunction. METHODS: HD (n = 17), FTD (n = 33) and AD (n = 13) patients were diagnosed according to international consensus criteria and, with healthy controls (n = 17), were scanned on the same MRI scanner. Patients underwent brief cognitive testing using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Ten MRI scans from this dataset were manually segmented as a training set for the Adaboost algorithm, which automatically segmented all remaining scans for the putamen, yielding the following subset of the data: 9 left and 12 right putamen segmentations for AD; 25 left and 26 right putamina for FTD; 16 left and 15 right putamina for HD; 12 left and 12 right putamina for controls. Shape analysis was performed at each point on the surface of each structure using a multiple regression controlling for age and sex to compare radial distance across diagnostic groups. RESULTS: Age, but not sex and intracranial volume (ICV), were significantly different in the segmentation subgroups by diagnosis. The AD group showed significantly poorer performance on cognitive testing than FTD. Mean putaminal volumes were HD < FTD < AD ≤ controls, controlling for age and ICV. The greatest putaminal shape deflation was evident in HD, followed by FTD, in regions corresponding to the interconnections to motoric cortex. CONCLUSIONS: Differential patterns of putaminal atrophy in HD, FTD and AD, with relevance to corticostriatal circuits, suggest the putamen may be a suitable clinical biomarker in neurodegenerative disease.

Surface-based TBM boosts power to detect disease effects on the brain: an N=804 ADNI study.

Computational anatomy methods are now widely used in clinical neuroimaging to map the profile of disease effects on the brain and its clinical correlates. In Alzheimer's disease (AD), many research groups have modeled localized changes in hippocampal and lateral ventricular surfaces, to provide candidate biomarkers of disease progression for drug trials. We combined the power of parametric surface modeling and tensor-based morphometry to study hippocampal differences associated with AD and mild cognitive impairment (MCI) in 490 subjects (97 AD, 245 MCI, 148 controls) and ventricular differences in 804 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI; 184 AD, 391 MCI, 229 controls). We aimed to show that a new multivariate surface statistic based on multivariate tensor-based morphometry (mTBM) and radial distance provides a more powerful way to detect localized anatomical differences than conventional surface-based analysis. In our experiments, we studied correlations between hippocampal atrophy and ventricular enlargement and clinical measures and cerebrospinal fluid biomarkers. The new multivariate statistics gave better effect sizes for detecting morphometric differences, relative to other statistics including radial distance, analysis of the surface tensor and the Jacobian determinant. In empirical tests using false discovery rate curves, smaller sample sizes were needed to detect associations with diagnosis. The analysis pipeline is generic and automated. It may be applied to analyze other brain subcortical structures including the caudate nucleus and putamen. This publically available software may boost power for morphometric studies of subcortical structures in the brain.

Accurate measurement of brain changes in longitudinal MRI scans using tensor-based morphometry.

This paper responds to Thompson and Holland (2011), who challenged our tensor-based morphometry (TBM) method for estimating rates of brain changes in serial MRI from 431 subjects scanned every 6 months, for 2 years. Thompson and Holland noted an unexplained jump in our atrophy rate estimates: an offset between 0 and 6 months that may bias clinical trial power calculations. We identified why this jump occurs and propose a solution. By enforcing inverse-consistency in our TBM method, the offset dropped from 1.4% to 0.28%, giving plausible anatomical trajectories. Transitivity error accounted for the minimal remaining offset. Drug trial sample size estimates with the revised TBM-derived metrics are highly competitive with other methods, though higher than previously reported sample size estimates by a factor of 1.6 to 2.4. Importantly, estimates are far below those given in the critique. To demonstrate a 25% slowing of atrophic rates with 80% power, 62 AD and 129 MCI subjects would be required for a 2-year trial, and 91 AD and 192 MCI subjects for a 1-year trial.

Imaging of the post-operative orbit and associated complications.

Dedicated post-operative radiological evaluation following ophthalmologic procedures is relatively uncommon. However, given the ever-growing ophthalmologic procedural advancements and the increasing utilization of neuroimaging for myriad indications, the orbits are often imaged incidentally in a delayed post-procedural state. Regardless of the clinical scenario, it is important for neuroradiologists and other specialists commonly exposed to orbital imaging to be aware of both expected and abnormal post-operative imaging findings because misinterpreted normal features or unrecognized complications can result in vision-threatening delays in treatment or mismanagement. In this review article, we discuss many common ophthalmologic procedures, their indications, and most likely complications. We also provide illustrative operative photographs and radiological imaging examples. By understanding the surgical intent, recognizing the devices that are commonly used, and developing familiarity with the appearance of post-operative complications, pitfalls in interpretation can be avoided and patient outcomes ultimately improved.

Takotsubo Cardiomyopathy Associated with Polycythemia Vera.

Takotsubo cardiomyopathy is characterized by transient apical ballooning with preserved basal ventricular function triggered by physical or emotional stressors. We present a case of a 75-year-old man referred to our facility for the management of acute myocardial infarction later diagnosed as takotsubo cardiomyopathy. We believe platelet-mediated adrenaline release from massive thrombocytosis might have been the precipitating factor for the pathogenesis of takotsubo cardiomyopathy.

Perioperative genitourinary infection associated with sodium-glucose co-transporter 2 inhibitor use.

Context: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel treatment approved for type 2 diabetes mellitus to lower hyperglycemia, systolic blood pressure, and promote weight loss. Commonly reported serious adverse events include increased mycotic urogenital infections, orthostatic hypotension, and normoglycemic ketoacidosis. Case report: We present a case of a 47-year old man with a history of type 2 diabetes mellitus initiated on the SGLT-2 inhibitor canagliflozin preoperatively before a penile implant, who presented with late postoperative MRSA bacteremia and scrotal abscess requiring implant extraction. Conclusion: As the SGLT-2 inhibitors are gaining in popularity, prescribers must be aware of the potential adverse genitourinary infectious outcomes. Providers should use caution and avoid initiating SGLT-2 inhibitors in the perioperative setting, and may even consider holding or discontinuing this medication in the setting of impending GU surgery.

Low back pain after a dental procedure: a case of Streptococcus viridans vertebral osteomyelitis.

Vertebral osteomyelitis due to Streptococcus viridans following a dental procedure is a rarely reported phenomenon. We discuss the case of a 67-year-old immunocompetent woman who presented with low back pain of 3 weeks duration associated with subjective fever and chills. On admission, the MRI of the lumbar spine showed L5-S1 vertebral osteomyelitis with associated paravertebral and epidural abscesses. Subsequently, detailed history was retaken and the patient reported having had a maxillary tooth extraction followed by a dental implant 2 months prior to the onset of her symptoms. Blood and abscess fluid cultures grew S. viridans Transthoracic echocardiogram showed no evidence of endocarditis. The patient was started on intravenous ceftriaxone but her treatment course was complicated by agranulocytosis requiring a switch to vancomycin. She required a total of 9 weeks of intravenous antibiotics for complete clinical cure.