Intrinsic Brain Activity in Temporal Lobe Epilepsy With and Without Depression: Insights From EEG Microstates

Background: Depression is the most common psychiatric comorbidity of temporal lobe epilepsy (TLE). In the recent years, studies have focused on the common pathogenesis of TLE and depression. However, few of the studies focused on the dynamic characteristics of TLE with depression. We tested the hypotheses that there exist abnormalities in microstates in patients with TLE with depression.Methods: Participants were classified into patients with TLE with depression (PDS) (n = 19) and patients with TLE without depression (nPDS) (n = 19) based upon the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). Microstate analysis was applied based on 256-channel electroencephalography (EEG) to detect the dynamic changes in whole brain. The coverage (proportion of time spent in each state), frequency of occurrence, and duration (average time of each state) were calculated.Results: Patients with PDS showed a shorter mean microstate duration with higher mean occurrence per second compared to patients with nPDS. There was no difference between the two groups in the coverage of microstate A–D.Conclusion: This is the first study to present the temporal fluctuations of EEG topography in comorbid depression in TLE using EEG microstate analysis. The temporal characteristics of the four canonical EEG microstates were significantly altered in patients with TLE suffer from comorbid depression.

The molecular pathogenesis of repeat expansion diseases

Expanded short tandem repeats in the genome cause various monogenic diseases, particularly neurological disorders. Since the discovery of a CGG repeat expansion in the FMR1 gene in 1991, more than 40 repeat expansion diseases have been identified to date. In the coding repeat expansion diseases, in which the expanded repeat sequence is located in the coding regions of genes, the toxicity of repeat polypeptides, particularly misfolding and aggregation of proteins containing an expanded polyglutamine tract, have been the focus of investigation. On the other hand, in the non-coding repeat expansion diseases, in which the expanded repeat sequence is located in introns or untranslated regions, the toxicity of repeat RNAs has been the focus of investigation. Recently, these repeat RNAs were demonstrated to be translated into repeat polypeptides by the novel mechanism of repeat-associated non-AUG translation, which has extended the research direction of the pathological mechanisms of this disease entity to include polypeptide toxicity. Thus, a common pathogenesis has been suggested for both coding and non-coding repeat expansion diseases. In this review, we briefly outline the major pathogenic mechanisms of repeat expansion diseases, including a loss-of-function mechanism caused by repeat expansion, repeat RNA toxicity caused by RNA foci formation and protein sequestration, and toxicity by repeat polypeptides. We also discuss perturbation of the physiological liquid-liquid phase separation state caused by these repeat RNAs and repeat polypeptides, as well as potential therapeutic approaches against repeat expansion diseases.

Surgical outcomes in children under 10 years old in the treatment of congenital scoliosis due to single nonincarcerated thoracolumbar hemivertebra: according to the age at surgery

Purpose Hemivertebra is one of the common pathogenesis of congenital scoliosis. The timing of operation is undefined. Our study compared the surgical outcomes in children under age 10 years with scoliosis due to single nonincarcerated thoracolumbar hemivertebra according to the age at surgery. Methods From January 2009 to August 2017, we retrospectively investigated 34 consecutive cases of congenital scoliosis treated by posterior hemivertebra resection and fusion with pedicle screw fixation. All cases were divided into two groups according to the age at surgery and followed-up for at least 2 years, group 1 (≤ 5 years old), and group 2 (5 to 10 years old). Results The mean Cobb angle of the main curve was improved from 48.58° to 15.53° (68.05%) in group 1, and from 43.73° to 11.33° (75.43%) in group 2. The segmental curve was improved from 44.16° to 11.53° (74.64%) in group 1, and the segmental curve was consistent with the main curve in group 2. The mean segmental kyphosis was improved from 27.50° to 8.42° (67.40%) in group 1, and from 29.00° to 5.00° (84.73%) in group 2. Five patients developed distal adding-on, and four patients were found proximal junctional kyphosis during the follow-up. Conclusion Not all the deformities caused by single nonincarcerated thoracolumbar hemivertebra would progress greatly with the spinal growth. No significant statistical differences were found in the coronal and sagittal correction rate between the two groups. A limited delayed surgery after 5 years but before 10 years of age with close follow-up can achieve satisfied results.

An integrative transcriptional logic model of hepatic insulin resistance

Abnormalities of lipid/lipoprotein and glucose metabolism are hallmarks of hepatic insulin resistance in type 2 diabetes. The former antedate the latter, but the latter become progressively refractory to treatment and contribute to therapeutic failures. It’s unclear whether the two processes share a common pathogenesis and what underlies their progressive nature. In this study, we investigated the hypothesis that genes in the lipid/lipoprotein pathway and those in the glucose metabolic pathway are governed by different transcriptional regulatory logics that affect their response to physiologic (fasting/refeeding) as well as pathophysiologic cues (insulin resistance and hyperglycemia). To this end, we obtained genomic and transcriptomic maps of the key insulin-regulated transcription factor, FoxO1, and integrated them with those of CREB, PPAR-α, and glucocorticoid receptor. We found that glucose metabolic genes are primarily regulated by promoter and intergenic enhancers in a fasting-dependent manner, while lipid genes are regulated through fasting-dependent intron enhancers and fasting-independent enhancerless introns. Glucose genes also showed a remarkable transcriptional resiliency (i.e., the ability to compensate following constitutive FoxO1 ablation through an enrichment of active marks at shared PPAR-α/FoxO1 regulatory elements). Unexpectedly, insulin resistance and hyperglycemia were associated with a “spreading” of FoxO1 binding to enhancers and the emergence of unique target sites. We surmise that this unusual pattern correlates with the progressively intractable nature of hepatic insulin resistance. This transcriptional logic provides an integrated model to interpret the combined lipid and glucose abnormalities of type 2 diabetes.

CNTM-06. Individual Cerebrocerebellar Functional Network Analysis for Decoding the Symptomatological Dynamics of Posterior Fossa Syndrome

Posterior fossa syndrome (PFS) consists of three types of symptom (motoric, linguistic, and neurobehavioral) in patients with posterior fossa pathologies. The evolutional mechanism of this high cognitive syndromic complex from cerebellar origin remains unconfirmed. Previous studies analyzing PFS patients mostly focused on the association between structural abnormalities that occur during PFS, of which proximal efferent cerebellar pathway (pECP) injury appears to be the most common pathogenesis. However, structural imaging may not be sensitive enough to determine the dynamic course of PFS, since the symptomatology is primarily an output of cerebral operation. On the other hand, a network neuroscience approach using a mathematical model to extract information from functional imaging to generate interregional connectivity provides abundant evidence that the cerebellum is influential in modulating cerebral functions. This study applied a network approach to children with PFS. Scaling of each symptom domain was used to quantify the dynamics of the syndrome. An individual cerebrocerebellar functional network analysis was then performed to determine the network dynamics during PFS. Cross-validation of clinical neurophysiology and functional neuroscience suggested the critical role of the pECP within PFS from the network analysis. The employed approach was therefore useful in determining the complex clinical symptoms using individual functional network analysis, which bridges the gap between structural neuroimaging and clinical neurophysiology.

Osteosarcopenic obesity in cardiovascular patients. Controversial and open issues

See “Inflammaging in the pathogenesis of chronic non-communicable diseases”, Kim O. T. in Opinion of invited editor, pp. 54-55.The study of osteosarcopenic obesity (OSO) in patients with cardiovascular diseases (CVDs) in recent years has caused a dis-cussion on common pathogenesis of atherosclerosis, obesity, progressive loss of skeletal and muscle mass. Are these processes independent age-related conditions or comorbidities with common links of pathogenesis? The aim of this review was to analyze studies on OSO in patients with CVDs. We used following electronic databases: PubMed, Clinical Trials, Google Scholar, www.elibrary.ru. Based on this analysis, modern ideas on the etiology, epidemiology and pathogenesis of OSO in elderly and senile patients with atherosclerosis were described. The authors concluded that absence of standards for OSO diagnosis and inadequate clinical suspicion of specialists during routine examination is one of the main causes of its insufficient detection in elderly patients with CVDs. The results of analyzed studies allow us to consider the OSO and atherosclerotic changes as a single link of cardiovascular continuum. Eliminating the negative effect of chronic inflammation on human body should be considered as a key mechanism in the treatment of OSO and atherosclerosis. However, more research is needed in this area.

Controversials of Microscopic Colitis

Microscopic colitis (MC) has become a disease with increased awareness due to the availability of new data about the pathogenesis, diagnosis and therapy of this disease. The incidence of MC is increasing, reaching the incidence of the inflammatory bowel disease (IBD) in some populations. However, some aspects of MC are still controversial. It is unknown whether the changes of microbiome play a role in the pathogenesis and what is in the background of the different subtypes of disease that can transform into each other. Is there a connection between MC and IBD or why the histological changes do not follow the clinical activity? We do not know what the etiology of the incomplete MC is, and what its natural course is. The association of MC with celiac disease is well-known- is there a common pathogenesis? The MC treatment is budesonide. Its effectiveness is high, but the relapse rate is high, as well. Why would biologics be effective in these cases when budesonide is not? This mini-review makes an attempt to summarize the data about MC and highlight that there are still unanswered questions in the pathogenesis, diagnosis and therapy of the disease, which can initiate further investigations in the future.

Surgical Outcomes in Children Under 10 Years Old in The Treatment of Congenital Scoliosis Due To Single Nonincarcerated Thoracolumbar Hemivertebra: According To The Age At Surgery

Purpose Hemivertebra is one of the common pathogenesis of congenital scoliosis. The timing of operation is undefined. Our study compared the surgical outcomes in children under age 10 years with scoliosis due to single nonincarcerated thoracolumbar hemivertebra according to the age at surgery. Methods From January 2009 to August 2017, we retrospectively investigated 34 consecutive cases of congenital scoliosis treated by posterior hemivertebra resection and fusion with pedicle screw fixation. All cases were devided into two groups according to the age at surgery and followed-up for at least 2 years. Group 1 (≤ 5 years old), and group 2 (5 to 10 years old). Results The mean Cobb angle of the main curve was improved from 48.58° to 15.53° (68.05%) in group 1, and from 43.73° to 11.33°(75.43%) in group 2. The segmental curve was improved from 44.16° to 11.53°(74.64 %) in group 1, and the segmental curve was consistent with the main curve in group 2. The mean segmental kyphosis was improved from 27.50° to 8.42°(67.40%) in group 1, and from 29.00° to 5.00° (84.73%) in group 2. 5 patients developed distal adding-on and 4 patients were found proximal junctional kyphosis during the follow up. Conclusions Not all the deformities caused by single nonincarcerated thoracolumbar hemivertebra would progress greatly with the spinal growth. A limited delayed surgery after 5 years but before 10 years of age with close follow-up can achieve good results, the occurrence of distal adding-on might be reduced, although it may need more than two segments fusion.

Posttraumatic subarachnoid hemorrhage related to concomitant carotid artery dissection and ruptured basilar trunk aneurysm: A case report and literature review

Background: Carotid artery dissections (CADs) are a relatively rare disorder, whereas intracranial aneurysms (IAs) form a common cerebrovascular pathology. Since both vascular entities share similar risk factors and associations with connective tissue and vascular disorders, a common pathogenesis has been suggested. Here, we present a case of the concomitant occurrence of a CAD and a ruptured basilar trunk aneurysm (BTA). In the discussion, we elaborate on both vascular entities and have reviewed the literature on their concomitant incidence and potential shared pathogenesis. Case Description: We present a case of a 40-year-old female patient who was admitted to our hospital because of subarachnoid hemorrhage following a minor head trauma. Imaging revealed a BTA and unilateral extracranial dissection of the internal carotid artery. Despite coiling of the aneurysm, stenting of the dissection, and antithrombotic therapy, the patient died due to extensive cerebral ischemia sequelae. Conclusion: CAD and BTAs have both been associated with a vascular vulnerability but their concomitant occurrence has not been described previously. The previous studies have suggested an increased incidence of IAs in patients with a CAD and vice versa. However, the number of studies and reports on this mutual increased incidence is limited. Therefore, a shared pathogenesis seems rather speculative. In our case, we suggest that a posttraumatic CAD-induced hemodynamic alterations resulting in rupture of the saccular BTA.

NMDAR in bladder smooth muscle is not a pharmacotherapy target for overactive bladder in mice

Overactive bladder (OAB) is a common condition that affects a significant patient population. The N-methyl-D-aspartate receptor (NMDAR) has a role in developing bladder overactivity, pharmacological inhibition of which inhibits bladder overactivity. The common pathogenesis of OAB involves bladder smooth muscle (BSM) overactivity. In this study, a smooth muscle–specific NMDAR knockout (SMNRKO) mouse model was generated. The bladders from SMNRKO mice displayed normal size and weight with an intact bladder wall and well-arranged BSM bundles. Besides, SMNRKO mice had normal voiding patterns and urodynamics and BSM contractility, indicating that NMDAR in BSM was not essential for normal physiological bladder morphology and function. Unexpectedly, cyclophosphamide (CYP)-treated SMNRKO and wild-type (WT) mice had similar pathological changes in the bladder. Furthermore, SMNRKO mice displayed similar altered voiding patterns and urodynamic abnormalities and impaired BSM contractility compared with WT mice after CYP treatment. MK801 partially reversed the pathological bladder morphology and improved bladder dysfunction induced by CYP, but did not cause apparent differences between WT mice and SMNRKO mice, suggesting that NMDAR in BSM was not involved in pathological bladder morphology and function. Moreover, the direct instillation of NMDAR agonists or antagonists into the CYP-induced OAB did not affect bladder urodynamic function, indicating that NMDAR in BSM was not the pharmacotherapy target of MK801 for CYP-induced cystitis. The findings indicated that NMDAR in BSM was not essential for normal physiological or pathological bladder morphology and function, and MK801 improving pathological bladder function was not mediated by an action on NMDAR in BSM.