Regional Dysfunction Research Articles

Invariant structural and functional brain regions associated with tinnitus: A meta-analysis.

Tinnitus is a common, functionally disabling condition of often unknown etiology. Neuroimaging research to better understand tinnitus is emerging but remains limited in scope. Voxel-based physiology (VBP) studies detect tinnitus-associated pathophysiology by group-wise contrast (tinnitus vs controls) of resting-state indices of hemodynamics, metabolism, and neurovascular coupling. Voxel-based morphometry (VBM) detects tinnitus-associated neurodegeneration by group-wise contrast of structural MRI. Both VBP and VBM studies routinely report results as atlas-referenced coordinates, suitable for coordinate-based meta-analysis (CBMA). Here, 17 resting-state VBP and 8 VBM reports of tinnitus-associated regional alterations were meta-analyzed using activation likelihood estimation (ALE). Acknowledging the need for data-driven insights, ALEs were performed at two levels of statistical rigor: corrected for multiple comparisons and uncorrected. The corrected ALE applied cluster-level inference thresholding by intensity (z-score > 1.96; p < 0.05) followed by family-wise error correction for multiple comparisons (p < .05, 1000 permutations) and fail-safe correction for missing data. The corrected analysis identified one significant cluster comprising five foci in the posterior cingulate gyrus and precuneus, that is, not within the primary or secondary auditory cortices. The uncorrected ALE identified additional regions within auditory and cognitive processing networks. Taken together, tinnitus is likely a dysfunction of regions spanning multiple canonical networks that may serve to increase individuals’ interoceptive awareness of the tinnitus sound, decrease capacity to switch cognitive sets, and prevent behavioral and cognitive attention to other stimuli. It is noteworthy that the most robust tinnitus-related abnormalities are not in the auditory system, contradicting collective findings of task-activation literature in tinnitus.

Post-systolic shortening index by echocardiography evaluation of dyssynchrony in the non-dilated and hypertrophied left ventricle

Abstract Background Post-systolic shortening index (PSI) is defined as myocardial shortening that occurs after aortic valve closure, and is an emerging measure of regional LV contractile dysfunction. PSI measurement variability amongst software vendor and its relationship with mechanical dyssynchrony and mechanical dispersion index (MDI) remains unknown. We evaluated PSI by speckle-tracking echocardiography from several vendors in patients with increased left ventricular wall thickness, and associations with MDI. Methods This is a prospective cross-sectional study of 70 patients (36 hypertrophic cardiomyopathy [HCM], 18 cardiac amyloidosis and 16 healthy controls) undergoing clinically indicated echocardiography. PSI was measured using QLAB/aCMQ (Philips), QLAB/LV auto-trace (Philips), EchoPAC (GE), Velocity Vector Imaging (Siemens), and EchoInsight (EPSILON) software packages, and calculated as 100% × (post systolic strain − end-systole strain)/post systolic strain. Results There was a significant difference in mean PSI among controls 2.1±0.6%, HCM 6.1±2.6% and cardiac amyloidosis 6.8±2.7% (p&amp;lt;0.001). Variations between software vendors were significant in patients with pathologic increases in LV wall thickness (for HCM p=0.03, for amyloidosis p=0.008), but not in controls (p=0.11), as seen in Figure 1. Furthermore, there were moderate correlations between PSI and both MDI (r=0.77) and left ventricular global longitudinal strain (r=0.69), as seen in Figure 2. Conclusion PSI was greater in HCM and cardiac amyloidosis patients than controls, and a valuable tool for dyssynchrony evaluation, with moderate correlations to MDI and strain. However, there were significant variations in PSI measurements by software vendor especially in patients with pathological increase in LV wall thickness, suggesting that separate vendor-specific thresholds for abnormal PSI are required. Funding Acknowledgement Type of funding sources: None.

Mitral annulus strain by 3D echo reveals regional annular dysfunction in Barlow's disease

Abstract Background Barlow's disease (BD) provides both diagnostic and therapeutic challenges. Annular dilation is typically seen in BD, however, data on regional deformation is lacking. Purpose We hypothesized that mitral annulus dilates non-homogenously during ventricular systole in BD. A method to calculate annular regional strain was developed and applied in a subset of BD patients and healthy controls. Methods Ten patients with BD and late systolic mitral regurgitation and nine healthy controls were studied. For each subject, the mitral annulus was segmented throughout the cardiac cycle using 3D echocardiography. Twelve evenly distributed geometrical points were annotated along the annular perimeter, enabling the creation of periodic degree-3 spline curves parameterized by arc length at each discrete time-frame. The motion of the mitral annulus was then acquired by assuming that heterogeneity in annular strain is small and finding the point-wise map that minimized the total displacement between the consecutive curves. Then, the end-diastolic annular curve was divided into 200 evenly distributed points around the annular perimeter, and the point-wise mapping was implemented to create a continuous movement of the discretized annulus throughout the cycle. Annular strain was then calculated for each individual line segment. The method presented herein is validated by comparing the strain between sonomicrometric crystals in pigs and the method described above. The timescale was normalized from ED (end-diastole) to mitral valve opening for each individual. The regional strains of the annulus were calculated with the ED configuration as reference. Results Hemodynamic data are presented in Table 1. In BD annulus area increased from 16.6±3.2 to 21.7±4.2 cm2 at end-diastole and peak systole, respectively (p&amp;lt;0.001). In controls, annulus area at end-diastole and end-systole was 9.6±2.2 cm2 and 9.2±1.8 cm2, respectively (NS). Figure 1 demonstrates non-homogenous regional strain at peak systole, with the most severe deformation in the posteromedial region. In healthy controls, peak systolic strain was similar in all segments. Conclusions In the present study, we have applied a novel non-invasive method to demonstrate non-homogenous deformation of the mitral annulus in Barlow patients. On average, the most severe deformation was seen in the posteromedial region. This finding may reveal further insight into the mechanisms of late systolic mitral regurgitation in BD as well as the design of annuloplasty in the future. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Trond Mohn Foundation

Impact of left bundle branch block in patients with takotsubo cardiomyopathy

Abstract Background Takotsubo cardiomyopathy (TCM) is a syndrome characterized by reversible left-ventricular regional systolic dysfunction in the absence of obstructive coronary artery disease (CAD). The presence of left bundle branch block (LBBB) has been described as an independent predictor of mortality in patients with CAD. One study using the National Inpatient Sample (NIS) for 2016 found that the presence of LBBB was associated with worse outcomes in patients with TCM. Purpose To better clarify the association between LBBB and various in-hospital outcomes in patients with TCM. Methods The NIS database was queried from 2016–2019 to identify all admissions with a primary diagnosis of TCM that had a cardiac catheterization to improve the specificity of the diagnosis. International classification of diseases, tenth revision clinical modification (ICD-10-CM) codes were used to divide patients based on the presence or absence of LBBB. A 1:3 propensity score matching based on age, race, gender, and risk factor stratification was used to reduce selection bias. Multivariate linear and logistic regression analysis was performed to compare various outcomes among both groups. Results A total of 27,125 patients admitted with a primary diagnosis of TCM that also underwent diagnostic coronary angiography were identified. In the study sample, 955 (3.5%) were determined to have a LBBB. After calculating propensity scores, 955 patients with LBBB were paired to 2,865 patients without LBBB. LBBB was associated with higher rates of ventricular arrhythmias (AOR=3.098, 95% CI 1.483–6.471, p=0.003); however, it was not statistically associated with cardiogenic shock, sudden cardiac arrest (SCA), acute kidney injury, acute heart failure, and hospital length of stay. In addition, there was no statistical difference in intra-hospital mortality. Conclusions LBBB is associated with left ventricular dyssynchrony. It has been proposed that intraventricular dyssynchrony might be a predisposing factor for ventricular arrhythmias (VA) and SCA. Several trials have demonstrated that cardiac resynchronization therapy alone (i.e., without defibrillation) reduces the rate of VA and SCA. The mechanism for this improvement is unclear but may be related to hemodynamic improvement from ventricular synchrony in heart failure (HF). In fact, LBBB has been reported as an independent risk factor for all-cause mortality and SCA at one year in patients with HF. Our analysis did not find any significant association between LBBB and SCA but did find an association with VA. Moreover, there were not enough events of intra-hospital mortality to assess a possible association between LBBB and mortality. Therefore, a prospective study with a longer follow-up would be needed to clarify the role of LBBB in mortality and establish causality between LBBB and VA in patients with TCM. Funding Acknowledgement Type of funding sources: None.

Molecular imaging of alphaVbeta3 integrin for evaluation of myocardial injury after acute myocardial infarction

Abstract Background 68Ga-NODAGA-RGD is a positron emission tomography (PET) tracer targeting αvβ3 integrin that is upregulated during angiogenesis. αvβ3 integrin expression increases early after acute myocardial infarction (AMI), and has been proposed as a marker of myocardial repair. Purpose We prospectively evaluated the uptake of 68Ga-NODAGA-RGD and its association to left ventricular function after human AMI. Methods Thirty patients underwent PET at 7.7±3.8 days after primary percutaneous coronary intervention for ST-elevation AMI. Resting myocardial perfusion was evaluated using 15O-water PET followed by evaluation of 68Ga-NODAGA-RGD uptake 60–75 minutes after injection of 179 MBq of tracer. Left ventricular function was evaluated by transthoracic echocardiography on the day of PET, and at 6-month follow-up. The definition of the ischemic area at risk and remote myocardial segments was based on the culprit coronary arterial segments in invasive angiography. 68Ga-NODAGA-RGD images were co-registered with perfusion images and uptake was measured as the standardized uptake value in the segment with the highest uptake (SUVmax) in ischemic area at risk, and the mean standardized uptake value (SUVmean) in remote segments. In addition, we calculated 68Ga-NODAGA-RGD uptake corrected to the mean myocardial blood flow (MBF) in the area at risk (SUVmax/MBFmean) to account for reduced distribution of tracer in non-viable tissue. Results Mean age of patients was 64±9 years, and 90% were males. Uptake of 68Ga-NODAGA-RGD was low in the remote myocardium, but focally increased in the ischemic area at risk (Figure 1). SUVmax in the ischemic area at risk was higher than SUVmean of the remote myocardium (0.73±0.16 vs. 0.51±0.11, p&amp;lt;0.001). 68Ga-NODAGA-RGD SUVmax did not correlate with MBF in the area at risk. Univariable predictors of 68Ga-NODAGA-RGD SUVmax in the area at risk included peak Troponin T (p&amp;lt;0.001), peak pro-BNP (p&amp;lt;0.001), low global longitudinal strain (p=0.01), and low regional longitudinal strain in the area at risk (p=0.02). In multivariable analysis, peak pro-BNP independently predicted SUVmax in the area at risk (p&amp;lt;0.001). At follow-up, left ventricular ejection fraction increased by 1.6±6.9% and global longitudinal strain by 0.5±3.2%. In univariable analysis, SUVmax and SUVmax/MBFmean in the area at risk predicted improvement of global longitudinal strain at 6 months after AMI (p=0.04 and p&amp;lt;0.001, respectively). Conclusion 68Ga-NODAGA-RGD uptake shows increased αvβ3 integrin expression in the ischemic area at risk early after reperfused AMI that is associated with the extent of myocardial injury, both regional and global systolic dysfunction, and increased left ventricular filling pressure. Increased 68Ga-NODAGA-RGD uptake in ischemic myocardium at risk predicts left ventricular function improvement at 6 months after AMI. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Academy of Finland, Finnish Foundation for Cardiovascular Research

Combining CRISPR-Cas9 and brain imaging to study the link from genes to molecules to networks

Receptors, transporters, and ion channels are important targets for therapy development in neurological diseases, but their mechanistic role in pathogenesis is often poorly understood. Gene editing and invivo imaging approaches will help to identify the molecular and functional role of these targets and the consequence of their regional dysfunction on the whole-brain level. We combine CRISPR-Cas9 gene editing with invivo positron emission tomography (PET) and functional MRI (fMRI) to investigate the direct link between genes, molecules, and the brain connectome. The extensive knowledge of the Slc18a2 gene encoding the vesicular monoamine transporter (VMAT2), involved in the storage and release of dopamine, makes it an excellent target for studying the gene network relationships while structurally preserving neuronal integrity and function. We edited the Slc18a2 in the substantia nigra pars compacta of adult rats and used invivo molecular imaging besides behavioral, histological, and biochemical assessments to characterize the CRISPR-Cas9-mediated VMAT2 knockdown. Simultaneous PET/fMRI was performed to investigate molecular and functional brain alterations. We found that stage-specific adaptations of brain functional connectivity follow the selective impairment of presynaptic dopamine storage and release. Our study reveals that recruiting different brain networks is an early response to the dopaminergic dysfunction preceding neuronal cell loss. Our combinatorial approach is a tool to investigate the impact of specific genes on brain molecular and functional dynamics, which will help to develop tailored therapies for normalizing brain function.

Chronic high-fat diet induces overeating and impairs synaptic transmission in feeding-related brain regions.

Obesity is linked to overeating, which can exacerbate unhealthy weight gain. However, the mechanisms for mediating such linkages are elusive. In the current study, we hypothesized that synaptic remodeling occurs in feeding-related brain regions of obese mice. To investigate this, we established a high-fat diet (HFD)-induced obese mouse model and observed that these mice consumed excessive calories. The effect of chronic HFD feeding on lipid droplet accumulation in different brain structures was also investigated. We found that lipid droplets accumulated on the ependyma of the third ventricle (3V), which is surrounded by key areas of the hypothalamus that are involved in feeding. Then, the spontaneous synaptic activity of miniature excitatory postsynaptic current (mEPSC) and miniature inhibitory postsynaptic current (mIPSC) was recorded in these hypothalamic areas. HFD induced a decreased amplitude of mEPSC in the arcuate nucleus (ARC) and the ventromedial hypothalamus (VMH), meanwhile, increased the frequency in the VMH. In addition, HFD reduced the frequency of mIPSC in the lateral hypothalamus (LH) and increased the amplitude of mIPSC in the paraventricular nucleus of the hypothalamus (PVH). Subsequently, we also measured the synaptic activity of nucleus accumbens (NAc) neurons, which play a vital role in the hedonic aspect of eating, and discovered that HFD diminished the frequency of both mEPSC and mIPSC in the NAc. These findings suggest that chronic HFD feeding leads to lipid accumulation and synaptic dysfunction in specific brain regions, which are associated with energy homeostasis and reward regulation, and these impairments may lead to the overeating of obesity.

Post-systolic shortening index by echocardiography evaluation of dyssynchrony in the non-dilated and hypertrophied left ventricle.

Post-systolic shortening index (PSI) is defined as myocardial shortening that occurs after aortic valve closure, and is an emerging measure of regional LV contractile dysfunction. PSI measurement variability amongst software vendor and its relationship with mechanical dyssynchrony and mechanical dispersion index (MDI) remains unknown. We evaluated PSI by speckle-tracking echocardiography from several vendors in patients with increased left ventricular wall thickness, and associations with MDI. This is a prospective cross-sectional study of 70 patients (36 hypertrophic cardiomyopathy [HCM], 18 cardiac amyloidosis and 16 healthy controls) undergoing clinically indicated echocardiography. PSI was measured using QLAB/aCMQ (Philips), QLAB/LV auto-trace (Philips), EchoPAC (GE), Velocity Vector Imaging (Siemens), and EchoInsight (EPSILON) software packages, and calculated as 100%×(post systolic strain-end-systole strain)/post systolic strain. There was a significant difference in mean PSI among controls 2.1±0.6%, HCM 6.1±2.6% and cardiac amyloidosis 6.8±2.7% (p <0.001). Variations between software vendors were significant in patients with pathologic increases in LV wall thickness (for HCM p = 0.03, for amyloidosis p = 0.008), but not in controls (p = 0.11). Furthermore, there were moderate correlations between PSI and both MDI (r = 0.77) and left ventricular global longitudinal strain (r = 0.69). PSI was greater in HCM and cardiac amyloidosis patients than controls, and a valuable tool for dyssynchrony evaluation, with moderate correlations to MDI and strain. However, there were significant variations in PSI measurements by software vendor especially in patients with pathological increase in LV wall thickness, suggesting that separate vendor-specific thresholds for abnormal PSI are required.

Which is responsible for aphasia by subcortical lesions? Subcortical lesions or the cortical hypoperfusion?

ABSTRACT Cerebral lesions causing aphasia involve morphological and functional changes. In this study, it was aimed to explain the connection between aphasia and subcortical lesions with SPECT. The study included 30 patients diagnosed in the first three days of stroke with a single hemorrhagic or ischemic lesion in the dominant hemisphere subcortical area. Gulhane Aphasia Test and SPECT were performed. Aphasia was detected in 19 cases (63.3%). The relationship between aphasia and perfusion dysfunction in cortical and subcortical regions of the brain was evaluated, aphasia was found to be present in 15 (71.4%) of the 21 patients with cortical hypoperfusion in the dominant hemisphere and 4 (44.4%) of the 9 patients without cortical hypoperfusion; the difference was not statistically significant (p = 0.16). In the ischemia group, aphasia was present in 11 (78.5%) of the 14 cases with cortical hypoperfusion in the dominant hemisphere. Aphasia wasn’t detected in any of the 5 cases that did not have cortical hypoperfusion, the difference was statistically significant (p = 0.005). When cerebral regions were evaluated separately, significant difference was reported in the aphasia seen with frontal, anterior parietal, and occipital hypoperfusion compared to cases with normal perfusion in these areas, with p = 0.003, p = 0.021, and p = 0.004, respectively. This study showed that aphasia to be more common in cases with cortical hypoperfusion in the dominant hemisphere than in cases without hypoperfusion. Our results provide evidence that direct effect of the lesion in the basal ganglia on the development of aphasia is doubtful.

Reverse Takotsubo Cardiomyopathy in a Patient With Commotio Cordis

Takotsubo cardiomyopathy (TCM), also known as stress cardiomyopathy or “broken heart syndrome”, is characterized by acute transient regional left ventricular systolic dysfunction in the absence of obstructive coronary artery disease or acute plaque rupture. Atypical forms and rare anatomical variants can have different presentations; hence, recognition becomes more important. Prognosis is much more favorable if managed appropriately. An equally infrequent cause of cardiac arrest is commotio cordis (CC). This is defined as sudden cardiac death secondary to a blunt chest wall impact leading to ventricular arrhythmias. We report a case with findings of TCM and/or CC in a patient with a blunt chest trauma in the setting of motor vehicle accident.

Lupus myocarditis: review of current diagnostic modalities and their application in clinical practice.

Lupus myocarditis (LM) is a potentially fatal manifestation of SLE, occurring in 5-10% of patients. Clinical manifestations may vary from an unexplained tachycardia to fulminant congestive cardiac failure (CCF). With no single clinical or imaging modality being diagnostic, a rational and practical approach to the patient presenting with possible LM is essential. Markers of myocyte injury (including troponin I and creatine kinase) may be unelevated and do not exclude a diagnosis of LM. Findings on ECG are non-specific but remain essential to exclude other causes of CCF such as an acute coronary syndrome or conduction disorders. Echocardiographic modalities including wall motion abnormalities and speckle tracking echocardiography may demonstrate regional and/or global left ventricular dysfunction and is more sensitive than conventional echocardiography, especially early in the course of LM. Cardiac magnetic resonance imaging (CMRI) is regarded as the non-invasive diagnostic modality of choice in myocarditis. While more sensitive and specific than echocardiography, CMRI has certain limitations in the context of SLE, including technical challenges in acutely unwell and uncooperative patients, contraindications to gadolinium use in the context of renal impairment (including lupus nephritis) and limited literature regarding the application of recommended diagnostic CMRI criteria in SLE. Both echocardiography as well as CMRI may detect subclinical myocardial dysfunction and/or injury of which the clinical significance remains uncertain. Considering these challenges, a combined decision-making approach by rheumatologists and cardiologists interpreting diagnostic test results within the clinical context of the patient is essential to ensure an accurate, early diagnosis of LM.

Statistical shape modeling reveals the link between right ventricular shape, hemodynamic force, and myocardial function in patients with repaired tetralogy of Fallot.

Patients with repaired tetralogy of Fallot (rTOF) can develop chronic pulmonary insufficiency (PI) with right ventricular (RV) dilation, progressive RV dysfunction, and decreased exercise capacity. Pulmonary valve replacement (PVR) can help reduce the amount of PI and RV dilation; however, optimal timing remains controversial; a better understanding of rTOF pathophysiology is of fundamental importance to inform clinical management of patients with rTOF and optimal timing of PVR. In this study, we hypothesize a tight interplay between RV shape, intracardiac biomechanics, and ventricular function in patients with rTOF. To explore this hypothesis and derive quantitative measures, we combined statistical shape modeling with physics-based analysis of in vivo 4D flow data in 36 patients with rTOF. Our study demonstrated for the first time a correlation between regional RV shape variations, hemodynamic forces (HDF), and clinical dysfunction in patients with rTOF. The main findings of this work include 1) general increase in RV size, due to both volume overload and physiological growth, correlated with decrease in strain magnitude in the respective directions, and with increased QRS; 2) regional PI-induced remodeling accounted for ∼10% of the shape variability of the population, and was associated with increased diastolic HDF along the diaphragm-to-right ventricular outflow tract (RVOT) direction, resulting in a net RV deformation along the same direction and decreased tricuspid annular plane systolic excursion (TAPSE); and 3) three shape modes independently correlated with systolic HDF and exercise capacity. Identification of patients based on the shape variations described in this study could help identify those at risk for irreversible dysfunction and guide optimal timing of PVR.NEW & NOTEWORTHY We combine statistical shape modeling with physics-based analysis of 4D flow data to elucidate the interplay between RV shape, hemodynamic forces, and clinical dysfunction in repaired tetralogy of Fallot. We are the first to show that ventricular remodeling is related to hemodynamic force magnitude and direction, global and regional functional parameters, and exercise intolerance. Identification of patients based on the shape variations described in this study could help identify those at risk for irreversible dysfunction.

Takotsubo syndrome and impending thyroid storm: A case report and brief review of the literature

Stress cardiomyopathy also called Takotsubo cardiomyopathy is characterized by transient regional systolic dysfunction of the left ventricle with electrocardiographic changes and an increase in troponin levels imitating myocardial infarction, but in the absence of angiographic evidence of obstructive coronary artery disease. Although the exact causal process has not been determined, it has been mentioned in connection with thyroid diseases. We describe a woman's case that experienced severe chest pain along with electrical and analytical abnormalities. Significant ventricular dysfunction was present, and the invasive coronary angiography revealed no lesions, which was compatible with stress cardiomyopathy. Impending thyroid storm due to Graves’ disease was observed as a trigger and it is imperative to identify and treat any clinical variables that could put patients at risk for Takotsubo syndrome or have an impact on the course of their treatment.

Age-related no-go P300 amplitudes are moderated by exposure to early-life stress

Deficits in inhibitory control are common with advancing age and may underlie declines in other complex cognitive functions. The inhibitory P300 event-related potential (ERP) generally decreases in amplitude with age, reflecting deficits in inhibitory performance evaluation and adaptation, with possible generators including precentral and inferior frontal gyri and midcingulate and parietal cortex. Exposure to early-life stress (ELS) is also associated with deficits in inhibitory control, smaller P300 amplitudes, and dysfunction in regions associated with P300 generation. Although biopsychosocial effects of ELS are evident in older adulthood, the influence of ELS on neural processes in later life is unknown. In the current study, 13 young adults and 21 healthy older adults completed a high-accuracy go/no-go task and the Juvenile Victimization Questionnaire (JVQ), an indicator of ELS. Regression analyses revealed significant central-parietal models, with smaller P300 amplitudes predicted by both older age and greater exposure to ELS. Age group*ELS interactions moderated P300 prediction at central and centro-parietal electrodes, such that older age predicted smaller P300 amplitudes only in those with lower to moderate ELS. Amplitudes did not significantly differ by age in those with higher ELS. Post-hoc within-age group correlations showed that greater ELS was associated with smaller P300 amplitudes in young adults. However, greater ELS was modestly associated with larger central amplitudes in older adults, potentially suggestive of anterior age-related compensatory recruitment to maintain high task performance. These findings suggest long-lasting neural implications of ELS that interact with normative neuro-cognitive aging processes, such that ELS may be an important risk factor for age-related cognitive decline.

Radiographic and Clinical Analysis of Cranio-Maxillofacial Complications of Cavernous Sinus Thrombosis Among 256 COVID-19 Patients.

Background:A heavy burden of cranio-maxillofacial complications may be encountered in corona virus disease-2019 patients due to the associated coagulopathy and inflammatory consequences of the disease. This study aims to describe clinical and radiographic features of these complications in 256 patients who developed 1 or more of the following complications: cavernous sinus thrombosis, osteomyelitis or necrosis of the jaws.Methods:Clinical assessment of cranial nerve function and general clinical assessment were performed. Imaging techniques used were multi-slice computed tomography, magnetic resonance imaging, and MRI with contrast enhancement.Results:Thromboembolism of brain and facial blood vessels were associated with inflammation and necrosis. Multi-slice computed tomography/MR angiography showed thrombotic occlusions of the internal carotid artery in the area of the cavernous sinus, and in the ophthalmic veins. Cavernous sinus thrombosis was attributed to coagulopathy and, inflammation of the paranasal sinuses, especially sphenoiditis. A noticeable increase in the size of the cavernous sinus was detected. Compression of the cranial nerves in the cavernous sinus (CS) region causes dysfunction and pathology in the corresponding regions.

Comparison of the osteopathic status of children in the fi rst six months of life with regurgitation with functional disorders of the digestive system or perinatal damage of the nervous system

Introduction. Recently, the prevalence of functional disorders of the digestive system (FD DS) in children has increased. Regurgitation is one of the most common manifestations of FD DS, but also one of the symptoms of perinatal damage to the nervous system (PD NS). The most diffi cult diagnosis of FD DS is in newborns and children of the fi rst half of life, since there are age restrictions in the use of instrumental research methods. Osteopathic diagnostics of somatic dysfunctions can complement clinical and instrumental research methods in such children. No studies have been conducted to assess the osteopathic status of children in the fi rst six months of life with FD DS and PD NS. The aim of the study is to assess the osteopathic status of children in the fi rst six months of life with regurgitation and to compare the osteopathic status in children with functional disorders of the digestive system or perinatal NS damage.Materials and methods. There were examined 50 children aged 1 to 6 months with regurgitation. The patients were divided into 2 groups of 25 people in accordance with the criteria for inclusion in the study — the presence of a diagnosed FD DS or PD NS, vegeto-visceral syndrome. Anamnestic information was collected. A single osteopathic examination was conducted, according to the results of which the osteopathic status of children of both groups was compared.Results. It was found that regional somatic dysfunction of the neck region (somatic component) and local somatic dysfunctions of the thoracic diaphragm and sigmoid colon are the most common in the group of children with FD DS. Regional somatic dysfunctions of the head and neck region are the most common in patients with PD NS and vegeto-visceral syndrome, which could be associated with the development of central nervous system pathology.Conclusion. The obtained results allow to recommend the osteopathic diagnostics to clarify the possible cause of regurgitation with an aim to its subsequent osteopathic correction in children of the fi rst six months of life with FD DR and PD NS.

Altered Intrinsic Brain Activity in Patients With Toothache Using the Percent Amplitude of a Fluctuation Method: A Resting-State fMRI Study.

ObjectiveThe percent amplitude of fluctuation (PerAF) technique was utilized to evaluate the neural functions of specific cerebrum areas in patients with toothache (TA).Patients and MethodsAn aggregation of 18 patients with TA (eight males and 10 females) were included in the study. We also recruited 18 healthy controls (HCs; eight men and 10 women) aligned for sex and age. Resting functional magnetic resonance imaging (rs-fMRI) scans were obtained. Then, we utilized the PerAF method and a support vector machine (SVM) to analyze the image data and measure neural abnormalities in related cerebrum areas. Receiver operating characteristic (ROC) curve analysis was utilized to appraise the two data sets.ResultsThe PerAF signals in the right dorsolateral superior frontal gyrus (RDSFG) and the right posterior central gyrus (RPCG) of TA sufferers were lower than HC signals. These results may reveal neural dysfunctions in relevant cerebrum regions. The AUC values of PerAF in the two areas were 0.979 in the RDSFG and 0.979 in the RPCG. The SVM results suggested that PerAF could be utilized to distinguish the TA group from HCs with a sensitivity of 75.00%, a specificity of 66.67%, and an accuracy of 70.83%.ConclusionPatients with TA had marked differences in PerAF values in some regions of the cerebrum. Changes in PerAF values represented distinctions in blood oxygen level dependent semaphore intensity, which reflected the overactivity or inactivation of some cerebrum areas in those suffering from TA. At the same time, we analyzed the PerAF values of TAs with ROC curve, which can be helpful for the diagnosis of TA severity and subsequent treatment. Our results may help to elucidate the pathological mechanism of TA.

Altered spontaneous brain activity in major depressive disorder: An activation likelihood estimation meta-analysis

BackgroundWide application of resting-state functional magnetic resonance imaging (fMRI) in psychiatric research has revealed that major depressive disorder (MDD) manifest abnormal neural activities in several brain regions involving key resting state networks. However, inconsistent results have hampered our understanding of the exact neuropathology associated with MDD. Therefore, our aim was to conduct a meta-analysis to identify the consistent vulnerable brain regions of MDD in resting state, and to reveal the potential pathogenesis of MDD. MethodsA systematic review analysis was conducted on studies involving brain resting-state changes in MDD using low-frequency amplitude (ALFF), fractional low-frequency amplitude (fALFF) and regional homogeneity (ReHo) analysis. The meta-analysis was based on the activation likelihood estimation method, using the software of Ginger ALE 2.3. Results25 studies (892 MDD and 799 healthy controls) were included. Based on the meta-analysis results of ReHo, we found robust reduction of resting-state spontaneous brain activity in MDD, including the left cuneus and right middle occipital gyrus (cluster size = 216, 256 mm3, uncorrected P < 0.0001), while no increased spontaneous activation in any of the brain regions. We also found reduced ALFF in the left middle occipital gyrus (cluster size = 224 mm3, uncorrected P < 0.0001), and no increased spontaneous brain activation in any regions. ConclusionOur meta-analysis study using the activation likelihood estimation method demonstrated that MDD showed significant abnormalities in spontaneous neural activity, compared with healthy controls, mainly in areas associated with visual processing, such as the cuneus and the middle occipital gyrus. Dysfunction of these brain regions may be one of the pathogenesis of MDD.

Is the pathology of posterior cortical atrophy clinically predictable?

Posterior cortical atrophy (PCA) is a neurodegenerative disorder characterized by an early prominent deficit of visual functions associated with signs and symptoms that are the expression of dysfunction of posterior brain regions. Although PCA is commonly associated with Alzheimer's disease (AD), in recent years new pathological substrates have emerged. Among them, frontotemporal lobar degeneration (FTLD) is the most commonly reported but, to date, little is known about the clinical features of PCA due to FTLD. We conducted a systematic search in the main biomedical database MEDLINE. We searched for all clinical PCA reports that assessed the pathological basis of such syndrome with at least one of the following: (1) neuropathological examination, (2) cerebrospinal fluid biomarkers, (3) amyloid-PET imaging and (4) genetic testing. Of 369 potentially eligible studies, 40 fulfilled the inclusion criteria with an overall number of 144 patients (127 PCA-AD vs. 17 PCA-FTD/non-AD). We found that hallucinations/illusions were present in none of the probable PCA-FTD/non-AD subjects while were reported in 15 out of 97 PCA-AD individuals. Optic ataxia and Parkinsonism showed a significantly greater prevalence in probable PCA FTD/non-AD than in PCA-AD whereas myoclonus and disorientation in time and space were significantly more frequent in PCA-AD than in probable PCA FTD/non-AD. We also found a predominance of a left-side pattern of atrophy/hypometabolism in the probable PCA FTD/non-AD. Clinical features such as optic ataxia, Parkinsonism, myoclonus, hallucinations and disorientation in time and space suggest the underlying pathological basis of PCA and help in leading the diagnostic protocol consequently.

Convergent and divergent gray matter volume abnormalities in unaffected first-degree relatives and ultra-high risk individuals of schizophrenia

High-risk populations of schizophrenia can be mainly identified as genetic high-risk based on putative endophenotypes or ultra-high-risk (UHR) based on clinically manifested symptoms. Previous studies have consistently shown brain structural abnormalities in both genetic high-risk and UHR individuals. In this study, we aimed to disentangle the convergent and divergent pattern of gray matter alterations between UHR and unaffected first-degree relatives from genetic high-risk individuals. We used structural MRI scans and voxel-based morphometry method to examine gray matter volume (GMV) differences among 23 UHR subjects meeting the Structured Interview for Prodromal Syndromes (SIPS) criteria, 18 unaffected first-degree relatives (UFDR), 26 first-episode schizophrenia patients (FES) and 54 healthy controls (CN). We found that a number of brain regions exhibited a monotonically decreasing trend of GMV from CN to UFDR to UHR to FES. Compared with CN, the UHR subjects showed significant decreases of GMV similar to the patients in the inferior temporal gyrus, fusiform gyrus, middle occipital gyrus, insula, and limbic regions. Moreover, the UHR transformed subgroup had significantly lower GMV than UHR non-transformed subgroup in the right inferior temporal/fusiform gyrus. On the other hand, the UFDR subjects only showed significant GMV decreases in the inferior temporal gyrus and fusiform. Moreover, we found GMV in the occipital lobe was negatively correlated with the UHR subjects’ composite positive symptom of SIPS, and GMV in the cerebellum was positively correlated with FES subjects’ symptom severity. Our results suggest that GMV deficits and regional dysfunction are evident prior to the onset of psychosis and are more prominent in the UHR than the UFDR individuals.