Clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis in patients with a long-term history of mental disorders.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder characterized by complex neuropsychiatric syndromes during disease onset. Although this disease has been well documented in the last decade, clinical characteristics of anti-NMDA receptor encephalitis in patients with long-term diagnostic history of mental disorders remain unclear. METHODS: Here, we reviewed and analyzed series of anti-NMDA receptor encephalitis patients with a long-term medical history of psychiatric disorders through a review of literature using PubMed, web of science and Embase database. In addition, we described a patient of anti-NMDA receptor encephalitis with a long-term history of major depressive disorder. RESULTS: A total of 14 patients with anti-NMDA receptor encephalitis and a long-term history of mental disorders were included in our study. We found that most patients were adult (92.9%) and female (78.6%). These patients often first visited a psychiatric department (71.43%). The mean disease course of psychiatric disorders was more than 9 years. Speech impairment (71.4%), abnormal behaviors (64.3%), and catatonia (64.3%) were the most common clinical symptoms. Most patients (85.7%) had a satisfactory prognosis after immunotherapy. CONCLUSION: Anti-NMDA receptor encephalitis in individuals with mental disorders is an underestimated condition, yet it presents complex clinical symptoms. Mental and behavioral impairments are more frequently observed in newly diagnosed anti-NMDA receptor encephalitis patients with a long-term history of mental disorders than those without mental illness. A diagnosis of anti-NMDA receptor encephalitis should be considered when patients with mental illness show sudden fluctuations in psychiatric symptoms.

Mild encephalitis/encephalopathy with a reversible splenial lesion associated with respiratory syncytial virus infection in infants.

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinicoradiologic syndrome typically characterized by transient mild encephalitis or encephalopathy with reversible lesions being found in the splenium of corpus callosum (SCC) by magnetic resonance imaging (MRI). A variety of pathogens including influenza virus, rotavirus, and adenovirus associated with MERS have been reported. However, respiratory syncytial virus (RSV)-related MERS is relatively rare in infants. In this study, we report two Chinese infants who suffered from RSV-related MERS. Both infants manifested as fever, seizure, and altered states of consciousness with confirmed detections of RSV-RNA in the specimens from throat swab. Clinical symptoms/signs such as apnea and shallow breathing were also noted in these two infants. Furthermore, brain MRI images indicated reversible isolated lesions with transiently reduced diffusion in the SCC. Fortunately, both of these two infants recovered completely following treatment within a month. Our study suggests that RSV may serve as a novel causative agent for MERS in infants. Clinicians should focus more attention on RSV-related MERS in infants in order to improve early accurate diagnosis and therapeutic decision making.

Efficacy of cattle encephalon glycoside and ignotin in patients with acute cerebral infarction: a randomized, double-blind, parallel-group, placebo-controlled study.

Cattle encephalon glycoside and ignotin (CEGI) injection is a compound preparation formed by a combination of muscle extract from healthy rabbits and brain gangliosides from cattle, and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries. However, there is still a need for high-level clinical evidence from large samples to support the use of CEGI. We therefore carried out a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016. The patients were randomized at a 3:1 ratio into CEGI (n = 239; 155 male, 84 female; 61.2 ± 9.2 years old) and placebo (n = 80; 46 male, 34 female; 63.2 ± 8.28 years old) groups. All patients were given standard care once daily for 14 days, including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium, both taken orally, and intravenous infusion of 250-500 mL 0.9% sodium chloride containing 40 mg sodium tanshinone IIA sulfonate. Based on conventional treatment, patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water, respectively, in an intravenous drip of 250 mL 0.9% sodium chloride (2 mL/min) once daily for 14 days. According to baseline National Institutes of Health Stroke Scale scores, patients in the two groups were divided into mild and moderate subgroups. Based on the modified Rankin Scale results, the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group, and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment. In the CEGI group, neurological deficits were decreased on days 14 and 90 after treatment, as measured by the National Institutes of Health Stroke Scale and the Barthel Index. Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients. No drug-related adverse events occurred in the CEGI or placebo groups. In conclusion, CEGI may be a safe and effective treatment for acute cerebral infarction patients, especially for moderate stroke patients. This study was approved by the Ethical Committee of Peking University Third Hospital, China (approval No. 2013-068-2) on May 20, 2013, and registered in the Chinese Clinical Trial Registry (registration No. ChiCTR1800017937).

Anti-N-methyl-D-aspartate receptor encephalitis mimics neuroleptic malignant syndrome: case report and literature review.

BACKGROUND: Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is a severe autoimmune disease characterized by complicated psychiatric and neurological symptoms and a difficult diagnosis. This disorder is commonly misdiagnosed, and diagnosis is often delayed. The clinical signs can mimic other psychiatric abnormalities, such as neuroleptic malignant syndrome (NMS) that is usually caused by antipsychotic exposure. This fact raises the question of whether the symptoms common to NMS are due to anti-NMDA receptor encephalitis or established NMS. CASES PRESENTATION: We describe a rare case of a 29-year-old male without psychiatric history who initially presented with a fever, altered consciousness, behavioral changes, rigidity, and elevated creatine kinase. He was initially diagnosed with NMS. NMS-like symptoms did not improve with active treatments and disappeared for a long period after discontinuing antipsychotics. The patient gradually developed a complicated disease progression, including speech impairment, mutism, and movement disorders, and symptom progression led to the final diagnosis of anti-NMDA receptor encephalitis. The related pathophysiological mechanisms, clinical features, and treatment of this disease are reviewed. CONCLUSION: We highlight that the natural progress of anti-NMDA receptor encephalitis can mimic the symptoms of NMS and NMS-like features could be due to anti-NMDA receptor encephalitis upon antipsychotic exposure, and not true NMS. Clinically, the suspicion of NMS may serve as a significant alarm to suspect anti-NMDA receptor encephalitis and lead neurologists or psychiatrists to investigate such a diagnosis.

p38 mitogen-activated protein kinase gene silencing rescues rat hippocampal neurons from ketamine-induced apoptosis: An in vitro study.

Ketamine (KTM) is an anesthetic drug with several advantages, including the elevation of cardiac output and blood pressure. However, KTM may also induce the apoptosis of hippocampal neurons. Notably, p38 mitogen­activated protein kinase (p38MAPK) has previously been studied for its role in neuronal injury. Therefore, the present study evaluated the effect of lentivirus­mediated p38MAPK gene silencing on KTM­induced apoptosis of rat hippocampal neurons. Hippocampal neurons were extracted from neonatal Sprague­Dawley rats, and then treated with KTM, p38MAPK­short hairpin RNA or SB203580 (an inhibitor of p38MAPK). Next, the expression levels of p38MAPK and apoptosis­associated genes, including caspase­3, B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein (Bax), were detected. In addition, cell viability and apoptosis were determined using an MTT assay and flow cytometry, respectively. Finally, telomerase activity of hippocampal neurons was detected by ELISA. The results revealed that silencing of p38MAPK in KTM­treated cells decreased the expression levels of p38MAPK, caspase­3 and Bax, and the extent of p38MAPK phosphorylation, while it increased the expression of Bcl­2. Furthermore, silencing p38MAPK promoted cell viability, cell cycle progression and the telomerase activity of hippocampal neurons, and inhibited the apoptosis of hippocampal neurons. Taken together, the results suggested an inhibitory role of lentivirus­mediated p38MAPK gene silencing on KTM­induced apoptosis of rat hippocampal neurons. Thus, p38MAPK gene silencing may serve as a potential target for preventing the KTM­induced apoptosis of hippocampal neurons.

Prefrontoparietal dysfunction during emotion regulation in anxiety disorder: a meta-analysis of functional magnetic resonance imaging studies.

OBJECTIVE: Impairments in emotion regulation, and more specifically in cognitive reappraisal, are thought to play a key role in the pathogenesis of anxiety disorders. However, the available evidence on such deficits is inconsistent. To further illustrate the neurobiological underpinnings of anxiety disorder, the present meta-analysis summarizes functional magnetic resonance imaging (fMRI) findings for cognitive reappraisal tasks and investigates related brain areas. METHODS: We performed a comprehensive series of meta-analyses of cognitive reappraisal fMRI studies contrasting patients with anxiety disorder with healthy control (HC) subjects, employing an anisotropic effect-size signed differential mapping approach. We also conducted a subgroup analysis of medication status, anxiety disorder subtype, data-processing software, and MRI field strengths. Meta-regression was used to explore the effects of demographics and clinical characteristics. Eight studies, with 11 datasets including 219 patients with anxiety disorder and 227 HC, were identified. RESULTS: Compared with HC, patients with anxiety disorder showed relatively decreased activation of the bilateral dorsomedial prefrontal cortex (dmPFC), bilateral dorsal anterior cingulate cortex (dACC), bilateral supplementary motor area (SMA), left ventromedial prefrontal cortex (vmPFC), bilateral parietal cortex, and left fusiform gyrus during cognitive reappraisal. The subgroup analysis, jackknife sensitivity analysis, heterogeneity analysis, and Egger's tests further confirmed these findings. CONCLUSIONS: Impaired cognitive reappraisal in anxiety disorder may be the consequence of hypo-activation of the prefrontoparietal network, consistent with insufficient top-down control. Our findings provide robust evidence that functional impairment in prefrontoparietal neuronal circuits may have a significant role in the pathogenesis of anxiety disorder.

Tangeretin alters neuronal apoptosis and ameliorates the severity of seizures in experimental epilepsy-induced rats by modulating apoptotic protein expressions, regulating matrix metalloproteinases, and activating the PI3K/Akt cell survival pathway.

PURPOSE: Epilepsy is complex neural disarray categorized by recurring seizures. Despite recent advances in pharmacotherapies for epilepsy, its treatment remains a challenge due to the contrary effects of the drugs. As a result, the identification of novel anti-epileptic drugs (AEDs) with neuroprotective properties and few side effects is of great value. Thus, the present study assessed the treatment effects of tangeretin using a rat model of pilocarpine-induced epilepsy. MATERIALS AND METHODS: Separate groups of male Wistar rats received oral administrations of tangeretin at 50, 100, or 200mg/kg for 10 days and then, on the 10th day, they received an intraperitoneal injection of pilocarpine (30mg/kg). Subsequently, neuronal degeneration and apoptosis were assessed using Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay procedures. Additionally, the expressions of phosphatidylinositol-3-kinase (PI3K/Akt) pathway proteins, cleaved caspase-3, Bad, Bcl-2, Bcl-xL, and Bax were determined using Western blot analyses. RESULTS: Tangeretin reduced the seizure scores and latency to first seizure of the rats and effectively activated the pilocarpine-induced suppression of PI3K/Akt signaling. Additionally, tangeretin effectively regulated the levels of apoptosis-inducing factor (AIF) in mitochondria as well as the expressions of apoptotic pathway proteins. Seizure-induced elevations in the activities and expressions of matrix metalloproteinases (MMPs)-2 and -9 were also modulated. CONCLUSION: The present results indicate that tangeretin exerted potent neuroprotective effects against pilocarpine-induced seizures via the activation of PI3K/Akt signaling and the regulation of MMPs.