Severe Regional Abnormalities Research Articles

Alzheimer’s disease is associated with increased modularity and assortativity: Evidence from structural and metabolic connectivity

AbstractBackgroundAlzheimer’s disease (AD) is a progressive disorder associated with cognitive dysfunction that alters brain connectivity and assessing these altered connectivity patterns has become a topic of increasing interest. In this study, we examine the structural and metabolic connectivity using cortical thickness and [18F] Flouro deoxyglucose (FDG)‐positron emission tomography (PET) to identify the network modification in patient with AD when compared to mild cognitive impairment (MCI). To examine our hypothesis; we quantified a relatively newer graph theory measures including assortativity and modularity. We aimed to unravel the multimodal network alterations using simultaneous MRI‐PET acquisitions.MethodsPatients who underwent simultaneous FDG‐PET and MRI study on a 3T MRI were recruited for this exploratory study. After appropriate pre‐processing of structural‐MRI and PET‐metabolic data, graph measures were obtained using the BRAPH toolbox, and subsequently; global and nodal network measures were used to derive group‐level differences (corrected p<0.05). Regions that revealed significant differences were correlated with the cognitive scores (ACE‐III).Results83 demographically matched patients [MCI (n = 27), and AD (n = 56)] were analysed. There were no significant differences between the groups in the mean age (MCI 63.52 ±9.19 years and AD 63.73 ±9.60 years), gender (M: F) MCI 20:7 and AD 26:30, or the mean duration of disease (MCI 2.23±1.92 and AD 2.95 years) other than ACE scores (MCI‐87.30±5.53 and AD 46.02 ±20.61, p value <0.001) and the CDR (MCI‐very mild and AD‐Moderate and Severe). Patients with AD revealed significantly increased assortativity at the global level in both structural and metabolic connectivity analysis. In addition, metabolic connectivity revealed increased modularity and decreased participation coefficient in patients with AD. Cortical thickness and SUV abnormalities in several regions in bilateral parietotemporal lobes were proportional with the cognitive scores (ACE‐III).ConclusionProbable erroneous and homophilic network segregation paralleling the aging associated loss of whole brain integration was found proportional to the memory scores. Further studies in larger cohorts are required to ascertain the clinical relevance of these findings as an imaging biomarker.

Castleman disease of the pancreas mimicking pancreatic malignancy on 68Ga-DOTATATE and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: A case report

BACKGROUNDCastleman disease is an uncommon nonclonal lymphoproliferative disorder, which frequently mimics both benign and malignant abnormalities in several regions. Depending on the number of lymph nodes or regions involved, Castleman disease (CD) varies in diagnosis, treatment and prognosis. It rarely occurs in the pancreas alone without any distinct clinical feature and tends to be confused with pancreatic paraganglioma (PGL), neuroendocrine tumors (NETs), and primary tumors, thus impeding proper diagnosis and treatment.CASE SUMMARYA 28-year-old woman presented with a lesion on the neck of the pancreas, detected by ultrasound during a health examination. Physical examination and laboratory findings were normal. The mass showed hypervascularity on enhanced computed tomography (CT), significantly increased 18F-fluorodeoxyglucose uptake on positron emission tomography (PET)/CT, and slightly increased somatostatin receptor (SSTR) expression on 68Ga-DOTATATE PET/CT, suggesting no distant metastases and subdiagnoses such as pancreatic PGL, NET, or primary tumor. Intraoperative pathology suggested lymphatic hyperplasia, and only simple tumor resection was performed. The patient was diagnosed with the hyaline vascular variant of CD, which was confirmed by postoperative immunohistochemistry. The patient was discharged successfully, and no recurrence was observed on regular review.CONCLUSIONHigh glucose uptake and slightly elevated SSTR expression are potentially new diagnostic features of CD of the pancreas.

Quantitative brain histogram of canine epilepsy using magnetic resonance imaging.

Quantitative magnetic resonance imaging (MRI) is used to study the anatomy of the brain in dogs with idiopathic epilepsy. To quantitate MRI images in terms of volumetric ratios and histogram analyses of the following regions of interest (ROI) in dogs with idiopathic epilepsy: frontal; parietal; temporal; piriform; thalamic; and hippocampal regions. Nine dogs with epilepsy and four healthy controls were evaluated. We examined the volumetric ratios and histogram analyses of six ROIs in all dogs. MR images, in T1-weighted, T2-weighted, FLAIR, diffusion-weighted imaging, and apparent diffusion coefficient sequences detected changes in 4/9 (44%) epileptic dogs found in 5/6 regions: frontal; parietal; temporal; piriform; and hippocampal regions. However, no such changes were observed in the thalamic region. Interestingly, the frontal and piriform volumetric ratios of epileptic dogs were significantly lower than those of control dogs. The histogram analyses in 4/6 regions were significantly increased in epileptic dogs. Our results demonstrated MRI finding abnormalities in several regions of the brain in several sequences including T1-weighted, T2-weighted, FLAIR, diffusion-weighted imaging, and apparent diffusion coefficient in epileptic dogs. In several regions of the brain, atrophy may exist, and hyperintensity may be present on MR images in epileptic dogs. These findings suggest that the diagnostic yield of MRI, which is an advanced neuroimaging technique, is high in epileptic dogs and has good reliability and sensitivity in detecting abnormal areas in patients.

Localization of cerebral hypoperfusion in dogs with refractory and non-refractory epilepsy using [99mTc] ethyl cysteinate dimer and single photon emission computed tomography.

To evaluate the localization of functional deficit area in epileptogenic zones of the brain in seven refractory and seven non-refractory epilepsy dogs using technetium 99m labeled with ethyl cysteinate dimer and interictal single photon emission computed tomography [99mTc-ECD SPECT] co-registration with Magnetic Resonance Imaging (MRI). Regions showing perfusion deficits in the SPECT images were analyzed by using the standard semiquantitative evaluation method to compare the level of cortical perfusion to the maximum number of counts within the cerebellum (max C), considered the area of reference. This study showed that SPECT imaging revealed abnormalities in several regions of the brain in both epilepsy groups. The refractory epilepsy dogs showed more frequency area of hypoperfusion in temporal lobe than non-refractory group with not statistically significance (P=0.28). The result suggests the lesion in temporal might be relevance with refractory epilepsy in canine patients.

Research on Major Depression

DEPRESSION IS AN ILLNESS THAT FREQUENTLY STARTS early in life, tends to run a chronic course, and produces substantial disability. According to the World Health Organization, depression is the leading global cause of years of life lived with disability and the fourth leading cause of disability-adjusted life-years, a measure that takes premature mortality into account. Depression is not only widespread and common, it may be fatal; an estimated 90% of suicides are associated with mental illness, most commonly depression. There were nearly 30000 suicides in the United States in 1999, almost twice the number of homicides. Suicide has become the third leading cause of death in individuals aged 15 to 24 years. Despite the high morbidity and mortality associated with depression, the etiology and pathophysiology of depression have not been precisely defined. Depression as currently diagnosed likely represents a heterogeneous set of disorders, usually characterized by sad mood and anhedonia (inability to experience pleasure), but often including profound abnormalities in cognition and neurovegetative, or physiological, function. Recent progress has occurred in identifying the neural circuits and neurochemicals involved in the vulnerability toward depressive illness. Neuroimaging studies have revealed abnormalities in several regions of the prefrontal cortex, amygdala, and hippocampus. Abnormalities in the regulation of neurotransmitters, including serotonin, norepinephrine, dopamine, glutamate, and -aminobutyric acid, and hormones and neuropeptides, such as cortisol, corticotrophin-releasing hormone, neuropeptide Y, and substance P, have been reported, any or all of which potentially suggest novel drug targets. However, none of these findings has resulted in a specific biomarker or diagnostic test for depression. In addition, vulnerability genes for depression have not been identified, although recently several genes associated with risk for other neuropsychiatric disorders have been reported. Depression is now recognized as a multisystem disorder affecting brain and body. It has been associated with alterations in endocrine, cardiovascular, and immune systems as well as changes in bone metabolism. These effects appear to have important medical consequences. For example, after a myocardial infarction, patients with depression have a 3.5-fold increase in cardiovascular mortality relative to patients without depression after a myocardial infarction. The impact of depression on post–myocardial infarction survival has been found to be at least equivalent to that of left ventricular dysfunction and history of previous myocardial infarction. Patients with depression also appear to be more likely to develop stroke, diabetes, and osteoporosis. Although the presence of depression has negative consequences on the prognosis of these illnesses, recent evidence suggests that treating depression may alter the course of comorbid medical illnesses. For instance, in patients with depression and diabetes, both antidepressants and cognitive behavior therapy decreased glycosylated hemoglobin levels. What is perhaps most remarkable about depression is there has been far more success in treating this illness than in understanding it. Antidepressants are generally effective, in that most studies demonstrate at least a 50% decrease in symptoms for about 70% of patients. Although all currently used antidepressants block uptake of 1 or more of the monoamines (serotonin, norepinephrine, or dopamine), the relationship of these neurochemical effects, which occur within hours, to the therapeutic effect, which requires several weeks, remains unclear. In addition to the medications used as antidepressants, specific structured psychotherapies have been shown to treat depression, particularly in less severe, nonpsychotic patients. What are the priorities and future directions for studies of depression? Last year the National Institute of Mental Health published a Strategic Plan for Mood Disorders that addressed this issue. The priority areas can be summarized as follows: Identify the vulnerability genes for depression. Several forms of depression have been identified based on clinical presentation. Some, such as bipolar disorder, are clearly heritable and undoubtedly polygenic. The discovery of the genes that confer vulnerability to bipolar disorder and other forms of depression may provide biomarkers, pathophysiological mechanisms, and new therapeutic targets.

Cerebral blood flow velocity and inflammatory response after severe traumatic brain injury

Objectives: The cerebral blood flow velocity (CBVF) was measured by transcranial Doppler sonography in patients with severe traumatic brain injury (TBI) in order to determine whether it depends on the posttraumatic inflammatory response. Material and methods: CBVF in both middle cerebral arteries (MCA) was recorded in 25 comatous TBI patients (male 20; female 5; mean age±SD, 41±20 years) and correlated to the levels of interleukine (IL) 6, IL-8 and IL-10 in corresponding CSF/plasma samples, to PaCO 2, and to intracranial (ICP), mean arterial (MAP) and cranial perfusion pressure (CPP). Results: CSF IL-6 and IL-8 were clearly higher than the corresponding plasma levels (mean CSF/plasma quotient for IL-6: 159±582; for IL-8: 143±311). CBVF did not show large side-to-side differences at each examination indicating that CBFV in both MCAs was determined mostly by systemic conditions and not by severe regional abnormalities. Because all other evaluated variables including interleukines represent also systemic conditions we used the mean value (MCBFV) of both CBFVs for analysis. By stepwise regression analysis between MCBVF (mean±SD, 80±26 cm/s) and the variables PaCO 2 (33±4 mmHg), MAP (86±12 mmHg), ICP (20±11 mmHg), CPP (70±14 mmHg), and CSF or plasma IL-6, IL-8, and IL-10 it turned out that MCBFV correlated significantly with PaCO 2 ( r=0.478; P<0.01) and CSF IL-8 ( r=−0.361; P<0.05). Conclusions: When CPP is adequate for brain perfusion, CBFV in the large brain supplying arteries depends predominantly on PaCO 2 and shows only a slight association to intrathecal IL-8 levels. For clinical interpretation of CBFV data the inflammatory response seems to be of minor relevance.