The transCampus Metabolic Training Programme Explores the Link of SARS-CoV-2 Virus to Metabolic Disease.

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.

Predictors of pharmacological treatment outcomes with atomoxetine or methylphenidate in patients with attention-deficit/hyperactivity disorder from China, Egypt, Lebanon, Russian Federation, Taiwan, and United Arab Emirates.

BACKGROUND: The reduced availability of data from non-Western countries limits our ability to understand attention-deficit/hyperactivity disorder (ADHD) treatment outcomes, specifically, adherence and persistence of ADHD in children and adolescents. This analysis assessed predictors of treatment outcomes in a non-Western cohort of patients with ADHD treated with atomoxetine or methylphenidate. METHODS: Data from a 12-month, prospective, observational study in outpatients aged 6-17 years treated with atomoxetine (N = 234) or methylphenidate (N = 221) were analysed post hoc to determine potential predictors of treatment outcomes. Participating countries included the Russian Federation, China, Taiwan, Egypt, United Arab Emirates and Lebanon. Factors associated with remission were analysed with stepwise multiple logistic regression and classification and regression trees (CART). Cox proportional hazards models with propensity score adjustment assessed differences in atomoxetine persistence among initial-dose cohorts. RESULTS: In patients treated with atomoxetine who had available dosing information (N = 134), Cox proportional hazards revealed lower (< 0.5 mg/kg) initial dose was significantly associated with shorter medication persistence (p < 0.01). multiple logistic regression analysis revealed greater rates of remission for atomoxetine-treated patients were associated with age (older), country (United Arab Emirates) and gender (female) (all p < 0.05). CART analysis confirmed older age and lack of specific phobias were associated with greater remission rates. For methylphenidate, greater baseline weight (highly correlated with the age factor found for atomoxetine) and prior atomoxetine use were associated with greater remission rates. CONCLUSIONS: These findings may help clinicians assess factors upon initiation of ADHD treatment to improve course prediction, proper dosing and treatment adherence and persistence. TRIAL REGISTRATION: Observational study, therefore no registration.

Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression.

This study takes advantage of continuing advances in the precision of magnetic resonance imaging (MRI) to quantify hippocampal volumes in a series of human subjects with a history of depression compared with controls. We sought to test the hypothesis that both age and duration of past depression would be inversely and independently correlated with hippocampal volume. A sample of 24 women ranging in age from 23 to 86 years with a history of recurrent major depression, but no medical comorbidity, and 24 case-matched controls underwent MRI scanning. Subjects with a history of depression (post-depressed) had smaller hippocampal volumes bilaterally than controls. Post-depressives also had smaller amygdala core nuclei volumes, and these volumes correlated with hippocampal volumes. In addition, post-depressives scored lower in verbal memory, a neuropsychological measure of hippocampal function, suggesting that the volume loss was related to an aspect of cognitive functioning. In contrast, there was no difference in overall brain size or general intellectual performance. Contrary to our initial hypothesis, there was no significant correlation between hippocampal volume and age in either post-depressive or control subjects, whereas there was a significant correlation with total lifetime duration of depression. This suggests that repeated stress during recurrent depressive episodes may result in cumulative hippocampal injury as reflected in volume loss.

Correlative assay of computerized cranial tomography CCT, water content and specific gravity in normal and pathological postmortem brain.

An assay of water content and specific gravity in normal and pathological autopsy brain has been correlated with CCT attenuation values obtained just prior to brain cutting. Formalin fixation does not alter normal values so that fixed brain appears to be suitable for this type of study. Low attenuation values in CCT correlate better with changes in specific gravity, rather than water in infarcts, but they have a close relationship to water content in edema. The high water content in infarcts of the white matter reveals a striking disparity in fluid control between cortex and white matter, which has not been emphasized in experimental studies. Water movement within and around blood clots has been discussed.

Correction of positron emission tomography data for cerebral atrophy.

Because positron emission tomography (PET) provides measurements per unit volume of intracranial contents, these measurements may be affected by the inclusion of metabolically inactive CSF spaces in the volume in which they are made. Thus, PET measurements of CBF and metabolism may be artifactually lowered in normal aging and dementia, which are both associated with significant brain atrophy. We describe a method to correct global PET data, averaged over several tomographic slices, for cerebral atrophy by using measurements of CSF space volume obtained with quantitative x-ray computed tomography. The importance of making such a correction is demonstrated using PET measurements of CBF and oxygen metabolism obtained in normal young, normal elderly, and demented subjects.

The effect of size, histologic elements, and water content on the visualization of cerebral infarcts.

We correlated the radiologic and pathologic examination of 13 human brains, analyzing the size, different histologic elements, and water content in 40 ischemic and hemorrhagic infarcts. Acute infarcts appear in the computerized cranial tomographic (CT) image as low density areas due to high content of fluid, however, a histological-chemical correlation is not concomitant. The addition of blood in hemorrhagic infarcts may result in a normal CT image. Subacute infarcts appear as low density areas, with lower attenuation values due to the presence of large amounts of lipids. Subacute lesions with prominent mineral deposits may be negative on CT scan. Chronic infarcts also appear as low density areas due to cavitation and residual fats. Attenuation values are slightly higher than those of subacute infarcts, possibly due to gliosis. Infarcts smaller than 2 cm in diameter are usually not visualized.

Computed tomography in chronic seizure disorder caused by glioma.

Since the introduction of computed tomography (CT) in 1974, 137 patients underwent cortical resection for intractable epilepsy. The CT scans of 32 of these patients demonstrated an isolated calcified or hypodense lesion of unknown origin. The mean interval from onset of the seizure disorder to surgery was 11 years. The referring physicians frequently considered these lesions to be of nonneoplastic origin, which usually delayed surgical management. Twenty-six of the 32 patients, however, proved to have a cerebral glioma, seven showing anaplastic changes. Because the majority of these patients were found to have a neoplasm and especially because the CT scan could not distinguish between a well-differentiated glioma and those with anaplastic changes, we recommend early surgical treatment in patients with chronic seizure disorders who are found to have an isolated lesion of unknown origin on CT scan.

Neurologic manifestations of glomus tumors in the head and neck.

In 75 patients with glomus tumors in the head and neck region, 57 tumors arose from the jugular bulb region, 11 from the middle ear, and seven from the vagus nerve. Thirty-seven percent (28 patients) had cranial nerve paralysis, and 14.6% (11) had intracranial tumor extension. The jugular foramen syndrome was associated with a 50% (two of four patients) incidence, and hypoglossal nerve paralysis with a 75% (three of four) incidence of posterior fossa tumor invasion. Horner syndrome and labyrinthine destruction had a 50% (two of four) incidence of a middle cranial fossa tumor invasion. The incidence of central nervous system (CNS) invasion with cranial nerve paralysis (excluding the seventh nerve) was 52% (11 of 21). Otologic findings and seventh nerve paralysis did not correlate with CNS tumor extension.

Osmotic demyelination syndrome. Lack of pathologic and radiologic imaging correlation.

An otherwise healthy diabetic woman developed severe hyponatremia, her serum sodium ion levels were rapidly corrected to normal, and she had a course of improvement then neurologic deterioration, with seizures and coma developing in the subsequent two days. Imaging studies, including computed tomography and magnetic resonance images of the brain as late as 19 days after the osmotic insult, failed to show pathologically demonstrated demyelinating lesions. Osmotic brain injury induces demyelination in areas of gray-white apposition and, clinically, results in a delayed neurologic deterioration one to three days following the osmotic challenge. Even with magnetic resonance imaging, review of the literature and this experience suggest that osmotic demyelination cannot reliably be imaged during the first month after the insult.

Schilder's (1912) disease. Total cerebral blindness due to acute demyelination.

A 51-year-old woman became blind from involvement of both occipital lobes with a confluent lesion demonstrated by computed tomographic scan. Biopsy showed demyelination consistent with Schilder's 1912 variant of diffuse sclerosis. No cytoplasmic inclusions were found on electron microscopy.

Correlation between regional cerebral blood flow and oxidative metabolism. In vivo studies in man.

To test the hypothesis that regional cerebral blood flow (rCBF) is normally regulated by regional metabolic activity, rCBF and the regional cerebral metabolic rate for oxygen (rCMRO2) were compared in selected human subjects. In normal subjects and patients with chronic, stable diseases of brain, rCBF correlated well with rCMRO2. In one individual with mild dementia, rCBF and rCMRO2 were measured before and during exercise of the hand and forearm contralateral to the hemisphere studied. Appropriate parallel changes occurred in both rCBF and rCMRO2 during hand exercise. In patients with acute diseases affecting the hemisphere studied, however, the correlation between rCBF and rCMRO2 was unpredictable.

Optimal utilization of computerized cranial tomography and radionuclide brain imaging.

The results of computerized cranial tomography and radionuclide brain imaging in 490 patients were compared in relationship to the patients' clinical presentation. In 195 patients with focal neurologic abnormalities, both tests detected most lesions, but computerized cranial tomography was slightly more accurate overall. Results of both studies were normal in 69 percent of 295 patients with nonfocal neurologic presentations, and radionuclide imaging failed to detect lesions in only five patients with nonfocal presentations. These results suggest that radionuclide imaging can be used to accurately screen most patients with nonfocal neurologic presentations. An exception is the patient presenting with dementia, in whom computerized cranial tomography provides details of the anatomy of the ventricular cavities and cerebral cortex. This study demonstrates a continuing role of importance for radionuclide imaging in the evaluation of patients with neurologic disease and provides data to allow a rational approach to the optimum use of both techniques.

Linear nevus sebaceous syndrome associated with porencephaly and nonfunctioning major cerebral venous sinuses.

An infant with the linear nevus sebaceous syndrome also had new findings of porencephaly and nonfunctioning major cerebral venous sinuses. This infant is the first described with the syndrome to undergo angiographic study. Similar nonfunctioning major cerebral venous sinuses are seen in the Sturge-Weber syndrome. A leptomeningeal angioma recently was reported in a newborn with the linear nevus sebaceous syndrome. The central nervous system disturbances in this syndrome might be secondary to developmental vascular anomalies. Therefore, the linear nevus sebaceous syndrome exhibits important similarities to the Sturge-Weber variety of neurocutaneous syndrome.

Periventricular white matter lucencies in senile dementia of the Alzheimer type and in normal aging.

The significance of periventricular lucencies in the white matter on CT in demented patients is not understood. We studied the relationship of these changes to mental status of subjects with senile dementia of the Alzheimer type. A semiquantitative method showed more numerous and extensive lucencies in demented than in healthy elderly. Neuropathologic examination of five subjects with these changes and confirmed Alzheimer's disease revealed diffuse white matter pallor without infarction. There were no hypertensive vascular changes, although limited hyaline thickening was present.

Coxsackie A9 focal encephalitis associated with acute infantile hemiplegia and porencephaly.

The factors underlying acute infantile hemiplegia are seldom identified. Coxsackie A9 focal encephalitis was documented for the first time in a 3-month-old infant with fever, hemiconvulsions, and hemiplegia followed by a static motor deficit and epilepsy. It has been suggested that the acute infantile hemiplegia associated with encephalitis results from an arteritis or venous sinus thrombosis with subsequent cerebral infarction. However, this was not observed in our patient. Rather, a series of brain scans, computerized tomograms, and a cerebral angiogram clearly documented the evolution of a focal necrotizing encephaloclastic process resulting in a porencephalic cyst. Serial cerebrospinal fluid viral cultures were necessary to isolate the etiologic agent (tcoxsackie A9). The infant did not have a neutralizing antibody response to the infecting viral agent despite an apparently intact immune system, which possibly may be explained by the developed of immune tolerance or an insufficient amount of infecting viral antigen. This emphasizes that serologic studies alone may not be adequate to document an acute central nervous system viral infection. This patient also typifies the poor prognosis in infants presenting with acute hemiplegia, fever, and convulsions in the absence of cerebrovascular occlusion.

Cerebral blood flow, oxygen utilization, and blood volume in dementia.

Patients with dementia had significant decreases in cerebral blood flow and cerebral oxygen utilization and a mild, but not significant, increase in cerebral blood volume. These studies were not useful in distinguishing patients with cerebral atrophy from patients with normal pressure hydrocephalus, as similar changes in cerebral circulation and metabolism were seen in both groups. Changes in cerebral blood flow after acute decrease in the intracranial pressure also were not helpful differentiating patients with normal pressure hydrocephalus from patients with cerebral atrophy.

Predictive features in mild senile dementia of the Alzheimer type.

Forty-three subjects with mild senile dementia of the Alzheimer type, diagnosed and staged by clinical research criteria, were studied with clinical, psychometric, EEG, visual evoked potential, and CT measures. During the 12 months following entry into the study, 21 subjects progressed to moderate or severe dementia, 21 remained mild, and one was lost to follow-up. Many of the clinical and psychometric measures of impairment were predictive of the progression to moderate or severe dementia. Electrophysiologic and CT measures were not. In a discriminant function analysis, the scores on two measures (the digit symbol subtest of the Wechsler Adult Intelligence Scale and an Aphasia Battery) correctly predicted the stage of dementia 1 year later in 95% of the subjects.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part III. Reliability of a standardized MRI evaluation of Alzheimer's disease.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed procedures for standardized imaging and reporting of magnetic resonance (MR) findings in Alzheimer's disease (AD) for use by neuroradiologists in multiple medical centers using a variety of MR equipment and field strengths. After initial pretesting, we revised the protocol, expanded the summary rating scale to seven points, and added more illustrations. Fourteen participating neuroradiologists evaluated 28 MR scans of elderly patients, giving us the basis for judging interrater agreement. We obtained acceptable intraclass correlations (greater than 0.79) for rating the size of the lateral and third ventricles and the temporal horn. Less satisfactory intraclass correlations occurred when rating other areas, including (1) global atrophy of the brain (0.70); (2) dilatation of the sulci of the temporal lobe (0.66); (3) frequency, location, and severity of white matter lesions (0.77); (4) sylvian fissure enlargement (0.70); and (5) cerebral sulcal dilatation (0.64). We also saw considerable variation in the reporting of cortical and lacunar infarcts. Despite careful design of the rating methodology and readings by experienced neuroradiologists, we did not find satisfactory interrater agreement for interpreting MR findings in elderly subjects. These findings may explain the difficulties encountered in applying similar subjective rating techniques that meet with success at one institution to multicenter studies. More objective and reproducible procedures are needed for interpretation of neuroimaging findings of AD in multicenter studies.

Correlation between computerized transaxial tomography and radionuclide cisternography in dementia.

A study of the findings on cisternograms and computerized transaxial tomography (CTT) of 144 patients showed good correlation between the two tests. Patients with a cisternographic pattern of communicating hydrocephalus tended to show more severe degrees of lateral ventricular dilation, with involvement of the third and fourth ventricles and relative sparing of the cerebral sulci. Patients with a cisternographic pattern of cerebral atrophy showed lesser degrees of lateral ventricular dilatation and more severe degrees of dilatation of the cerebral sulci. The statistical significance of the individual CTT findings in these patients is presented, and a cheme for interpretation is proposed. The study shows that CTT can replace pneumoencephalography in evaluating patients with dementia, while cisternography contributes complementary information.

Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus. Dementia of the Alzheimer type.

OBJECTIVE: To determine the feasibility of using high-dimensional brain mapping (HDBM) to assess the structure of the hippocampus in older human subjects, and to compare measurements of hippocampal volume and shape in subjects with early dementia of the Alzheimer type (DAT) and in healthy elderly and younger control subjects. BACKGROUND: HDBM represents the typical structures of the brain via the construction of templates and addresses their variability by probabilistic transformations applied to the templates. Local application of the transformations throughout the brain (i.e., high dimensionality) makes HDBM especially valuable for defining subtle deformities in brain structures such as the hippocampus. METHODS: MR scans were obtained in 18 subjects with very mild DAT, 18 healthy elderly subjects, and 15 healthy younger subjects. HDBM was used to obtain estimates of left and right hippocampal volume and eigenvectors that represented the principal dimensions of hippocampal shape differences among the subject groups. RESULTS: Hippocampal volume loss and shape deformities observed in subjects with DAT distinguished them from both elderly and younger control subjects. The pattern of hippocampal deformities in subjects with DAT was largely symmetric and suggested damage to the CA1 hippocampal subfield. Hippocampal shape changes were also observed in healthy elderly subjects, which distinguished them from healthy younger subjects. These shape changes occurred in a pattern distinct from the pattern seen in DAT and were not associated with substantial volume loss. CONCLUSIONS: Assessments of hippocampal volume and shape derived from HDBM may be useful in distinguishing early DAT from healthy aging.