Motor dysfunction in mild cognitive impairment as tested by kinematic analysis and transcranial magnetic stimulation

ObjectivePrevious studies have demonstrated voluntary movement alterations as well as motor cortex excitability and plasticity changes in patients with mild cognitive impairment (MCI). To investigate the pathophysiology of movement abnormalities in MCI, we tested possible relationships between movement abnormalities and primary motor cortex alterations in patients.MethodsFourteen amnestic MCI (aMCI) patients and 16 healthy controls were studied. Cognitive assessment was performed using clinical scales. Finger tapping was recorded by a motion analysis system. Transcranial magnetic stimulation was used to test the input/output curve of motor evoked potentials, intracortical inhibition, and short-latency afferent inhibition. Primary motor cortex plasticity was probed by theta burst stimulation. We investigated correlations between movement abnormalities, clinical scores, and cortical neurophysiological parameters.ResultsMCI patients showed less rhythmic movement but no other movement abnormalities. Cortical excitability measures were normal in patients, whereas plasticity was reduced. Movement rhythm abnormalities correlated with frontal dysfunction scores.ConclusionOur study in MCI patients demonstrated abnormal voluntary movement and plasticity changes, with no correlation between the two. Altered rhythm correlated with frontal dysfunction.SignificanceOur results contribute to the understanding of pathophysiological mechanisms of motor impairment in MCI.     

The endogenous inflammatory reflex inhibits the inflammatory response to different immune challenges in mice

The splanchnic anti-inflammatory pathway, the efferent arm of the endogenous inflammatory reflex, has been shown to suppress the acute inflammatory response of rats to systemic lipopolysaccharide (LPS). Here we show for the first time that this applies also to mice, and that the reflex may be engaged by a range of inflammatory stimuli. Experiments were performed on mice under deep anaesthesia. Half the animals were subjected to bilateral section of the splanchnic sympathetic nerves, to disconnect the splanchnic anti-inflammatory pathway, while the remainder underwent a sham operation. Mice were then challenged intravenously with one of three inflammatory stimuli: the toll-like receptor (TLR)-4 agonist, LPS (60 µg/kg), the TLR-3 agonist Polyinosinic:polycytidylic acid (Poly I:C, 1 mg/kg) or the TLR-2 and -6 agonist dipalmitoyl-S-glyceryl cysteine (Pam2cys, 34 µg/kg). Ninety minutes later, blood was sampled by cardiac puncture for serum cytokine analysis. The splanchnic anti-inflammatory reflex action was assessed by comparing cytokine levels between animals with cut versus those with intact splanchnic nerves. A consistent pattern emerged: Tumor necrosis factor (TNF) levels in response to all three challenges were raised by prior splanchnic nerve section, while levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were reduced. The raised TNF:IL-10 ratio after splanchnic nerve section indicates an enhanced inflammatory state when the reflex is disabled. These findings show for the first time that the inflammatory reflex drives a coordinated anti-inflammatory action also in mice, and demonstrate that its anti-inflammatory action is engaged, in similar fashion, by inflammatory stimuli mimicking a range of bacterial and viral infections.     

A study of unprotected left main intervention in the ACS population 2013–2018

ObjectivesOur objectives were to evaluate the outcomes of left main percutaneous coronary interventions in Acute Coronary Syndrome population.MethodsThis is a retrospective& observational study. Primary endpoint is a composite of death, stent thrombosis/MI, target lesion revascularization. Secondary endpoints include individual components of the primary events analyzed separately.ResultsSeventy five patients, two year follow – up data was analyzed. The primary event analysis showed that the Elective Double Stent (EDS) group had a higher primary events (36% vs. 14%, p value – 0.008, Hazard ratio – 0.76 (0.51–1.15, 95% CI), in secondary event analysis stent thrombosis (ST)/Myocardial infarction (MI) rates were higher in EDS group (8% Vs 36%, p Value – 0.008, Hazard ratio- 0.63(0.35–1.14, 95%CI), there is no difference in target lesion revascularization (TLR)and death rates in both the groups.ConclusionsThe provisional strategy is better than EDS in treatment of left main bifurcation lesions in the ACS population.     

Novel variants in aromatic L-amino acid decarboxylase deficiency: Case report of sisters with mild phenotype

BackgroundAromatic L-amino acid decarboxylase (AADC) deficiency, caused by a pathogenic variant in the dopa decarboxylase (DDC) gene, is a rare neurometabolic disorder in which catecholamine and serotonin are not synthesized. From a large number of reports, it has been recognized that most affected patients show severe developmental delay in a bedridden state and are unable to speak. On the other hand, patients with a mild phenotype with AADC deficiency have been reported, but they number only a few cases. Therefore, the variation of phenotypes of the disease appears to be broad, and it may be challenging to diagnose an atypical phenotype as AADC deficiency.Case reportWe report novel compound heterozygous variants in DDC (c.202G > A and c.254C > T) in two sisters, whose main complaint was mild developmental delay, by whole-exome sequencing (WES). Additionally, we describe their clinical features and provide an image that shows the variants located at different sites responsible for the catalysis of AADC in a three-dimensional structure. The patients were prescribed a Monoamine oxidase (MAO) inhibitor after diagnosis.InterpretationOur cases indicate that a comprehensive genomic approach helps to diagnose AADC deficiency with atypical features, and underscore the significance of understanding the variations of this disorder for diagnosis and appropriate treatment.     

Thymic epithelial tumor with superior vena cava syndrome diagnosed by percutaneous endovascular tumor biopsy: A report of two cases

Thymic epithelial tumor is a rare, potentially progressive disease that commonly infiltrates mediastinal structures. In rare cases, it may cause superior vena cava syndrome. Pretreatment histopathological diagnosis is essential to determine the most effective treatment strategy. Percutaneous endovascular biopsy is a rarely reported non-surgical diagnostic option for large vessel tumoral involvement. We report two cases of thymic epithelial tumor with superior vena cava syndrome diagnosed by percutaneous endovascular biopsy. No procedural complications occurred, and subsequent systemic treatment was promptly administered. This procedure may have potential as a useful diagnostic method for patients with mediastinal tumors involving large vessels.     

Mortality prediction in chronic obstructive pulmonary disease and obstructive sleep apnea

BackgroundWe aimed to assess mortality in chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), and overlap syndrome, and evaluate which polysomnographic indices—apnea-hypopnea index (AHI) or hypoxemic load measurements—better predict mortality within 10 years.MethodsAdults with symptoms suggestive of sleep apnea and airway disease who underwent both polysomnography and spirometry plus bronchodilator response tests between 2000 and 2018 were included and divided into four groups according to presence of COPD and moderate-to-severe OSA (AHI ≥15/h). We estimated mortality using a Cox model adjusted for demographic/anthropometric covariates and comorbidities; this was called clinical model. To evaluate prognostic performance, we compared the concordance index (C-index) between clinical model and extended models, which incorporated one of polysomnographic indices—AHI, sleep time spent with SpO₂ < 90% (TS90), and mean and lowest SpO₂.ResultsAmong 355 participants, patients with COPD alone (57/355, 16.1%) and COPD–OSA overlap syndrome (37/355, 10.4%) had increased all-cause mortality than those who had neither disease (152/355, 42.8%) (adjusted HR, 2.98 and 3.19, respectively). The C-indices of extended models with TS90 (%) and mean SpO₂ were significantly higher than that of clinical model (0.765 vs. 0.737 and 0.756 vs. 0.737, respectively; all P < 0.05); however, the C-index of extended model with AHI was not (0.739 vs. 0.737; P = 0.15).ConclusionsIn this cohort with symptoms of sleep apnea and airway disease, patients with overlap syndrome had increased mortality, but not higher than in those with COPD alone. The measurement of hypoxemic load, not AHI, better predicted mortality.     

Concurrent conventional & high-definition transcranial direct current stimulation for treatment of schizophrenia with co-morbid obsessive-compulsive disorder: A case report

Non-invasive brain stimulation techniques such as conventional transcranial direct current stimulation (tDCS) and high definition tDCS (HD-tDCS) are increasingly being used as add-on treatment options in schizophrenia and obsessive-compulsive disorder (OCD). This is reporting of the use of a novel accelerated, symptom-specific, add-on tDCS (combining conventional and high definition) protocol in a patient with both schizophrenia and OCD. The intervention showed clinical utility by reducing both schizophrenia and OCD symptoms.     

The pathology of gastric and duodenal polyps: current concepts

The liberal use of upper endoscopy has led to an increased detection of gastric and duodenal polyps, which are identified in as many as 6 and 4.6% of patient examinations, respectively. Gastroduodenal polyps are a heterogeneous group of lesions that can be neoplastic or non‐neoplastic (e.g. hyperplastic or heterotopical). Most polyps present characteristic topographical features, as well as endoscopic appearance and size. Evaluation of the surrounding mucosa is essential in assessing the underlying pathology (e.g. Helicobacter pylori, autoimmune gastritis or inherited polyposis syndromes). Phylogenetically, gastric and duodenal polyps can be classified according to the epithelial compartment from which they derive. Polyps that arise from the surface epithelium can either be of foveolar or intestinal type, and they can develop from either the native mucosa or the metaplastic epithelium (gastric intestinal metaplasia or duodenal foveolar metaplasia). Other polyps develop from the deeper glandular component, such as pyloric/oxyntic gland derived subtypes. In this review we focus upon epithelial polyps, with an emphasis on the most common and clinically relevant lesions, and present recently described entities.