Japanese Encephalitis Accompanied by Cerebral Venous Sinus Thrombosis: a Case Report

Background: Cerebral venous sinus thrombosis (CVST) is a relatively rare cerebrovascular condition which accounts for 0.5% of all strokes. Risk of CVST has been documented in patients with numerous conditions including central nervous system infections, however, Japanese encephalitis (JE, epidemic encephalitis type B) with CVST has not been reported previously. Case Presentation: Here, we present a case of JE with CVST in a 17-year-old man. On admission, the patient was initially diagnosed as intracranial infection, and soon after, brain magnetic resonance (MR) imaging (MRI) and MR Venography (MRV) confirmed the diagnosis of CVST. Moreover, the blood JE-specific IgM antibody which proved weakly positive at first, turned positive one week later. Consequently, our patient was diagnosed as CVST accompanied by JE. Anticoagulant and anti-infective therapy were initiated, which eventually lead to gradual recovery of the patient. Conclusions: To our knowledge, this is the first case report of CVST associated with JE. MRI and MRV represent a prime method for the diagnosis of CVST, while the positivity of JE virus IgM antibody, especially increased antibody levels within a short period, is of great significance to diagnose JE. The early diagnosis and timely treatment of this potentially lethal condition would improve its prognosis significantly

Long-Term Efficacy and Safety of Human Umbilical Cord Mesenchymal Stromal Cells in Rotenone-Induced Hemiparkinsonian Rats

Several studies have shown functional improvements, neuroprotective, and neuroregenerative effects after mesenchymal stem cells transplantation to parkinsonian animal models. However, questions remain about the safety, feasibility, and long-term efficacy of this approach. In this study, we investigated migration, therapeutic, tumorigenesis, and epileptogenic effects of human umbilical cord mesenchymal stromal cells (HUMSCs) 1 year after transplantation into rotenone-induced hemiparkinsonian rats. Our data indicated that DiI-labeled HUMSCs migrated in the lesioned hemisphere, from corpus striatum (CPu) to substantia nigra. By integrating with host cells and differentiating into NSE, GFAP, Nestin, and tyrosine hydroxylase-positive cells, HUMSCs prevented 48.4% dopamine neurons from degeneration and 56.9% dopamine terminals from loss, both correlating with improvement of apomorphine-induced rotations. The CD50 and CD97 value of pentylenetetrazol and semiquantitative immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), β-catenin, C-myc, and NF-κB expression showed no significant difference between HUMSCs transplanted and untransplanted groups, whereas the expressions of Bcl-2 and P53 in the grafted CPu were upregulated by 281% and 200% compared to ungrafted CPu. The results of this long-term study suggest that HUMSCs transplantation, 1 of the most potential treatments for Parkinson's disease, is an effective and safe approach

Glucocerebrosidase L444P Mutation Confers Genetic Risk for Parkinson’s Disease in Central China

Background: Mutations of the glucocerebrosidase (GBA) gene have reportedly been associated with Parkinson disease (PD) in various ethnic populations such as Singaporean, Japanese, Formosan, Canadian, American, Portuguese, Greek, Brazilian, British, Italian, Ashkenazi Jewish, southern and southwestern Chinese. The purpose of this study is to determine in central China whether or not the reported GBA mutations remain associated with PD. Methods: In this project, we conducted a controlled study in a cohort of 208 central Chinese PD patients and 298 controls for three known GBA mutations (L444P, N370S and R120W). Results: Our data reveals a significantly higher frequency of L444P mutation in GBA gene of PD cases (3.4%) compared with the controls (0.3%) (P = 0.007, OR = 10.34, 95% CI = 1.26 - 84.71). Specifically, the frequency of L444P mutation was higher in the late onset PD (LOPD) cases compared with that in control subjects. The N370S and R120W mutations were detected in neither the PD group nor the control subjects. Conclusions: Our observations demonstrated that the GBA L444P mutation confers genetic risk for PD, especially LOPD, among the population in the central China area

The Role of Autophagy in Parkinson's Disease: Rotenone-Based Modeling

Background: Autophagy-mediated self-digestion of cytoplasmic inclusions may be protective against neurodegenerative diseases such as Parkinson’s disease (PD). However, excessive autophagic activation evokes autophagic programmed cell death. Methods: In this study, we aimed at exploring the role of autophagy in the pathogenesis of rotenone-induced cellular and animal models for PD. Results: Reactive oxygen species over-generation, mitochondrial membrane potential reduction or apoptosis rate elevation occurred in a dose-dependent fashion in rotenone-treated human neuroblastoma cell line SH-SY5Y. The time- and dose-dependent increases in autophagic marker microtubule-associated protein1 light chain 3 (LC3) expression and decreases in autophagic adaptor protein P62 were observed in this cellular model. LC3-positive autophagic vacuoles were colocalized with alpha-synuclein-overexpressed aggregations. Moreover, the number of autophagic vacuoles was increased in rotenone-based PD models in vitro and in vivo. Conclusions: These data, along with our previous finding showing rotenone-induced toxicity was prevented by the autophagy enhancers and was aggravated by the autophagy inhibitors in SH-SY5Y, suggest that autophagy contributes to the pathogenesis of PD, attenuates the rotenone toxicity and possibly represents a new subcellular target for treating PD

MAPT rs242562 and GSK3B rs334558 are associated with Parkinson’s Disease in central China

Background: Microtubule-associated protein tau (MAPT) is a neuronal protein involved in the pathogenesis of several neurodegenerative diseases including Parkinson’s Disease (PD). Glycogen synthase kinase 3 beta (GSK3B) catalyzes phosphorylation in multiple sites of tau protein. However, whether or not there is any association between the GSK3B gene alteration, MAPT haplotype and PD remains unexplored in Chinese population, especially in central Chinese population. Results: Here, we aimed at studying the effect of MAPT rs242562 and GSK3B rs334558 on the risk of PD by performing a case-control association study in central China. Our data showed that all PD patients and controls were of MAPT H1/H1 diplotype in our study, thus confirming that the distribution of the MAPT H1 haplotype is common in China. GG genotype of MAPT rs242562 serves protection effect on PD risk in central Chinese population, while genotype of GSK3B rs334558 showed no difference between PD patients and controls. Conclusions: We conclude that the MAPT rs242562 is associated with PD in central China in the background of MAPT H1/H1 diplotype. The GG genotype of rs242562 displays protection against PD in subgroup with GSK3B rs334558 T carrier

Effectiveness of Traditional Chinese Medicine as an Adjunct Therapy for Parkinson’s Disease: A Systematic Review and Meta-Analysis

Background: Idiopathic Parkinson disease (PD) is a common neurodegenerative disease that seriously hinders limb activities and affects patients’ lives. We performed a meta-analysis aiming to systematically review and quantitatively synthesize the efficacy and safety of traditional Chinese medicine (TCM) as an adjunct therapy for clinical PD patients. Methods: An electronic search was conducted in PubMed, Cochrane Controlled Trials Register, China National Knowledge Infrastructure, Chinese Scientific Journals Database and Wanfang data to identify randomized trials evaluating TCM adjuvant therapy versus conventional treatment. The change from baseline of the Unified Parkinson’s Disease Rating Scale score (UPDRS) was used to estimate the effectiveness of the therapies. Results: Twenty-seven articles involving 2314 patients from 1999 to 2013 were included. Potentially marked improvements were shown in UPDRS I (SMD 0.68, 95%CI 0.38, 0.98), II (WMD 2.41, 95%CI 1.66, 2.62), III (WMD 2.45, 95%CI 2.03, 2.86), IV (WMD 0.32, 95%CI 0.15, 049) and I-IV total scores (WMD 6.18, 95%CI 5.06, 7.31) in patients with TCM plus dopamine replacement therapy (DRT) compared to DRT alone. Acupuncture add-on therapy was markedly beneficial for improving the UPDRS I–IV total score of PD patients (WMD 10.96, 95%CI 5.85, 16.07). However, TCM monotherapy did not improve the score. The effectiveness seemed to be more obvious in PD patients with longer adjunct durations. TCM adjuvant therapy was generally safe and well tolerated. Conclusions: Although the data were limited by methodological flaws in many studies, the evidence indicates the potential superiority of TCM as an alternative therapeutic for PD treatment and justifies further high-quality studies

New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease

Parkinson’s disease (PD) is one of the synucleinopathies spectrum of disorders typified by the presence of intraneuronal protein inclusions. It is primarily composed of misfolded and aggregated forms of alpha-synuclein (α-syn), the toxicity of which has been attributed to the transition from an α-helical conformation to a β-sheetrich structure that polymerizes to form toxic oligomers. This could spread and initiate the formation of “LB-like aggregates,” by transcellular mechanisms with seeding and subsequent permissive templating. This hypothesis postulates that α-syn is a prion-like pathological agent and responsible for the progression of Parkinson’s pathology. Moreover, the involvement of the inflammatory response in PD pathogenesis has been reported on the excessive microglial activation and production of pro-inflammatory cytokines. At last, we describe several treatment approaches that target the pathogenic α-syn protein, especially the oligomers, which are currently being tested in advanced animal experiments or are already in clinical trials. However, there are current challenges with therapies that target α-syn, for example, difficulties in identifying varying α-syn conformations within different individuals as well as both the cost and need of long-duration large trials

Exosomes and Their Therapeutic Potentials of Stem Cells

Exosomes, a group of vesicles originating from the multivesicular bodies (MVBs), are released into the extracellular space when MVBs fuse with the plasma membrane. Numerous studies indicate that exosomes play important roles in cell-to-cell communication, and exosomes from specific cell types and conditions display multiple functions such as exerting positive effects on regeneration in many tissues. It is widely accepted that the therapeutic potential of stem cells may be mediated largely by the paracrine factors, so harnessing the paracrine effects of stem and progenitor cells without affecting these living, replicating, and potentially pluripotent cell populations is an advantage in terms of safety and complexity. Ascending evidence indicated that exosomes might be the main components of paracrine factors; thus, understanding the role of exosomes in each subtype of stem cells is far-reaching. In this review, we discuss the functions of exosomes from different types of stem cells and emphasize the therapeutic potentials of exosomes, providing an alternative way of developing strategies to cure diseases

Postoperative ecchymoma of eyelid after botulinum toxin injection for hemifacial spasm: a case report

Hemifacial spasm (HFS) is a rare movement disorder characterized by involuntary muscle contractions on one side of the face. Compared to the high therapeutic effect, adverse effects of botulinum toxin treatment for HFS occurred rarely. However, managing HFS patients who are also taking antithrombotic drugs poses a challenge. Here, we present a case of postoperative ecchymoma of the eyelid following a botulinum toxin injection in a patient receiving daily vinpocetine and aspirin antiplatelet therapy. This case highlights the importance of considering the potential risks and formulating a treatment plan that maximizes benefit while minimizing complications in HFS patients undergoing botulinum toxin injections and taking antithrombotic medications. To the best of our knowledge, this is the first reported case of postoperative ecchymoma of the eyelid following a botulinum toxin injection. Further research and additional case reports are needed to better understand the management strategies for this patient population

Cluster-Like Headache Secondary to Anamnesis of Sphenoid Ridge Meningioma: A Case Report and Literature Review

Cluster headache is generally considered to be a primary headache; secondary cluster-like headache is quite rare, while cluster-like headache secondary to meningioma is even rarer. Here, we describe an unusual case with cluster-like headache 2.5 years after sphenoid ridge meningioma surgery. The cluster-like headache and meningioma were on the same side, and even at the same position. Furthermore, the cluster-like headache lasted for 6 months. In addition, the patient did not respond well to conventional treatments for cluster headache, such as oxygen inhalation, carbamazepine, and tramadol. Brain magnetic resonance imaging demonstrated a softening lesion, glial hyperplasia, and localized thickening and enhancement of the dura in the left frontal-temporal lobe. However, positron-emission computed tomography showed reduced metabolism in the left frontal-temporal lobe. Although the possibility of a primary headache cannot be completely eliminated, the association between cluster-like headache and probable tumor recurrence or postoperative changes should be considered