Valproate encephalopathy is one of the unusual and severe but treatable side effect. This research focuses on four female patients who had valproate medication for epilepsy and developed an increased frequency of seizures, exacerbated disruption of consciousness, gastrointestinal problems, cognitive dysfunction, ataxia, and psychobehavioral abnormalities. The patient\'s symptoms improved over time once sodium valproate was stopped. As a result, when using sodium valproate, one should be aware of the risk of sodium valproate encephalopathy and cease using the medication right once if any of the above symptoms of unknown etiology manifest clinically. We also go over the potential pathogenesis that lead to valproate encephalopathy and the heightened risk of encephalopathy from taking antiepileptic medications together. It was stressed how crucial it is to identify, diagnose, and treat sodium valproate encephalopathy as soon as possible.

UNASSIGNED: This study aims to systematically assess the risk factors, the overall strength of association, and evidence quality related to sepsis-associated encephalopathy.
UNASSIGNED: A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, and Embase for cohort or case-control studies published up to August 2023 on risk factors associated with sepsis-related encephalopathy. The selected studies were screened, data were extracted, and the quality was evaluated using the Newcastle-Ottawa Scale. Meta-analysis was performed using RevMan 5.3 software. The certainty of the evidence was assessed using the GRADE criteria.
UNASSIGNED: A total of 13 studies involving 1,906 participants were included in the analysis. Among these studies, 12 were of high quality, and one was of moderate quality. Our meta-analysis identified six risk factors significantly associated with Serious Adverse Events (SAE). These included APACHE II, SOFA, age, tau protein, and IL-6, which were found to be risk factors with significant effects (standard mean difference SMD: 1.24-2.30), and albumin, which was a risk factor with moderate effects (SMD: -0.55). However, the certainty of evidence for the risk factors identified in this meta-analysis ranged from low to medium.
UNASSIGNED: This systematic review and meta-analysis identified several risk factors with moderate to significant effects. APACHE II, SOFA, age, tau protein, IL-6, and albumin were associated with sepsis-related encephalopathy and were supported by medium- to high-quality evidence. These findings provide healthcare professionals with an evidence-based foundation for managing and treating hospitalized adult patients with sepsis-related encephalopathy.

Acute necrotizing encephalopathy (ANE) is a rare but deadly complication with an unclear pathogenesis. We aimed to elucidate the immune characteristics of H1N1 influenza virus-associated ANE (IANE) and provide a potential therapeutic approach for IANE. Seven pediatric cases from a concentrated outbreak of H1N1 influenza were included in this study. The patients\' CD4+ T cells from peripheral blood decreased sharply in number but highly expressed Eomesodermin (Eomes), CD69 and PD-1, companied with extremely high levels of IL-6, IL-8 in the cerebrospinal fluid and plasma. Patient 2, who showed high fever and seizures and was admitted to the hospital very early in the disease course, received intravenous tocilizumab and subsequently showed a reduction in temperature and a stable conscious state 24 h later. In conclusion, a proinflammatory cytokine storm associated with activated CD4+ T cells may cause severe brain pathology in IANE. Tocilizumab may be helpful in treating IANE.

UNASSIGNED: Sepsis is recognized as a multiorgan and systemic damage caused by dysregulated host response to infection. Its acute systemic inflammatory response highly resembles that of lipopolysaccharide (LPS)-induced endotoxemia. Propofol and dexmedetomidine are two commonly used sedatives for mechanical ventilation in critically ill patients and have been reported to alleviate cognitive impairment in many diseases. In this study, we aimed to explore and compare the effects of propofol and dexmedetomidine on the encephalopathy induced by endotoxemia and to investigate whether ferroptosis is involved, finally providing experimental evidence for multi-drug combination in septic sedation.
UNASSIGNED: A total of 218 C57BL/6J male mice (20-25 g, 6-8 weeks) were used. Morris water maze (MWM) tests were performed to evaluate whether propofol and dexmedetomidine attenuated LPS-induced cognitive deficits. Brain injury was evaluated using Nissl and Fluoro-Jade C (FJC) staining. Neuroinflammation was assessed by dihydroethidium (DHE) and DCFH-DA staining and by measuring the levels of three cytokines. The number of Iba1+ and GFAP+ cells was used to detect the activation of microglia and astrocytes. To explore the involvement of ferroptosis, the levels of ptgs2 and chac1; the content of iron, malondialdehyde (MDA), and glutathione (GSH); and the expression of ferroptosis-related proteins were investigated.
UNASSIGNED: The single use of propofol and dexmedetomidine mitigated LPS-induced cognitive impairment, while the combination showed poor performance. In alleviating endotoxemic neural loss and degeneration, the united sedative group exhibited the most potent capability. Both propofol and dexmedetomidine inhibited neuroinflammation, while propofol\'s effect was slightly weaker. All sedative groups reduced the neural apoptosis, inhibited the activation of microglia and astrocytes, and relieved neurologic ferroptosis. The combined group was most prominent in combating genetic and biochemical alterations of ferroptosis. Fpn1 may be at the core of endotoxemia-related ferroptosis activation.

The paper presents the summary of the spectrum of encephalopathy treated with acupuncture and moxibustion and the analysis on the existing questions in its clinical research, and proposes the potential strategies on treatment of encephalopathy with acupuncture and moxibustion. The spectrum of encephalopathy includes 23 diseases of central nervous system (superspinal center) and 33 kinds of mental and behavioral disorders. There are three problems in clinical research of acupuncture and moxibustion for encephalopathy, i.e. lack of high-quality clinical evidences, inadequate support from theoretic study of TCM and limited study on the rules of treatment. Hence, the author proposes five strategies on the treatment of encephalopathy with acupuncture and moxibustion, i.e. ① stimulating the peripheral nerve trunk associated with brain dysfunction, triggering the interaction between peripheral and central nerves and emphasizing the autonomic rehabilitation training to promote the reorganization of brain function; ② improving the cerebral circulation and metabolism by stimulating the trigeminal nerve and sphenopalatine ganglion; ③ stimulating the sites with high-dense distribution of peripheral nerve endings and the large projection area in the somatosensory region of the brain to induce strong brain responses, which may adjust the abnormal operation of the default mode network in the resting state; ④ stimulating the vagus nerve to improve the mood, suppressing the abnormal firing of brain neurons and stimulating the sites with the stellate ganglion distributed to modulate the hypothalamic function; ⑤ delivering the therapeutic regimens in association with the specific conditions and symptoms, and the classification of the physical signs on the base of the treatment of encephalopathy.
概述目前针灸治疗脑病的病谱，分析针灸治疗脑病临床研究存在的问题，提出针灸治疗脑病的可能策略。针灸治疗脑病的病谱包括23种中枢神经系统（脊髓上中枢）疾病和33种精神与行为障碍病症。针灸治疗脑病的临床研究存在3方面问题：高质量的临床证据不足、针灸治疗脑病的中医理论研究不足和针灸治疗脑病的规律研究不足。笔者提出针灸治疗脑病的五大策略，即刺激脑功能障碍相关的外周神经干，引发外周与中枢的交互作用，并强调自主性康复训练的重要意义，尽早促进脑功能重组；通过刺激三叉神经与蝶腭神经节来改善脑循环、脑代谢；刺激外周神经末梢分布密度高及在脑躯体感觉区投射面积大的部位，以引起较强的脑反应，从而可能对静息状态下脑默认模式网络的工作方式异常起到调整作用；刺激迷走神经改善情绪、抑制脑神经元异常放电，选择星状神经节刺激点以调节下丘脑功能；在治疗脑病的基础上，结合具体情况与症状、体征分类治疗。.

A 63-year-old man developed reduced consciousness and dysphagia progressively. Examination and parameters were normal, except for a Glasgow Coma Scale score of seven, and his grading on the swallow water test increased from grade 1 to grade 5. Brain imaging and blood tests were unexplainable except by high plasma ammonia. His past medical history included cerebral infarction, hypertension and epilepsy induced by cerebral hyperperfusion syndrome. He was rceiving antiepileptic treatment of continuously intravenously pumped sodium valproate of 64 mg/h for 4 days, which overlapped for 12 hours with taking 500 mg sustained release tablets. Sodium valproate was stopped; testing demonstrated normal plasma concentrations of sodium valproate and elevated concentrations of ammonia. Ornithine aspartate was administrated. The patient\'s level of responsiveness and ammonia levels gradually improved. The patient was also being treated with ceftriaxone sodium for a hypostatic pneumonia and with desmopressin for diabetes insipidus. There is an association between sodium valproate and hyperammonaemia and encephalopathy. Immediate recognition of the serious but uncommon adverse effects is essential. To our knowledge this is the first report of ornithine aspartate being used in this disorder.

Neuroinflammation and oxidative stress contribute to the progression of sepsis-associated encephalopathy (SAE). Angiotensin-converting enzyme 2 (ACE2) is considered to be a neuroprotective factor due to its anti-inflammatory and antioxidant properties. However, the role of ACE2 on myeloid cells in regulating SAE and the underlying mechanism warrants further exploration. SAE was induced in ACE2 transgenic (TG), knockout (KO), and bone marrow (BM) chimeric mice by cecal ligation and puncture (CLP). The expression levels of apoptosis-, oxidation- and neuroinflammation-associated mediators and morphological changes were monitored by quantitative real-time PCR analyses and histological examinations in the cortex of septic mice. The contents of angiotensin (Ang) II and Ang-(1-7) along with the activity of ACE2 were examined with commercial kits. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2 was detected by immunoblotting analysis. Our results indicated that the expression of cortical ACE2 was significantly reduced in the early phase of CLP-induced sepsis. Moreover, ACE2 overexpression in TG mice conferred neuroprotection against sepsis, as evidenced by alleviated neuronal apoptosis, oxidative stress, and proinflammatory M1-like microglial polarization, accompanied by upregulation of the Ang-(1-7), Nrf2, and Sestrin2 protein levels. Conversely, ACE2 deficiency in KO mice exacerbated SAE. The neuroprotective effects of ACE2 were further confirmed in wild-type mice transplanted with ACE2-TG and KO BM cells. Therefore, our data suggest that myeloid ACE2 exerts a protective role in the pathogenesis of SAE, potentially by activating Ang-(1-7)-Nrf2/sestrin2 signaling pathway, and highlight that upregulating ACE2 expression and activity may represent a promising approach for the treatment of SAE in patients with sepsis.

Sepsis-associated encephalopathy (SAE), a common neurological complication of sepsis, is a heterogenous complex clinical syndrome caused by the dysfunctional response of a host to infection. This dysfunctional response leads to excess mortality and morbidity worldwide. Despite clinical relevance with high incidence, there is a lack of understanding for its both its acute/chronic pathogenesis and therapeutic management. A better understanding of the molecular mechanisms behind SAE may provide tools to better enhance therapeutic efficacy. Mounting evidence indicates that some types of non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis, and autophagy, contribute to SAE. Targeting these types of RCD may provide meaningful targets for future treatments against SAE. This review summarizes the core mechanism by which non-apoptotic RCD leads to the pathogenesis of SAE. We focus on the emerging types of therapeutic compounds that can inhibit RCD and delineate their beneficial pharmacological effects against SAE. Within this review we suggest that pharmacological inhibition of non-apoptotic RCD may serve as a potential therapeutic strategy against SAE.

BACKGROUND: Dengue is an important public health problem, which caused by the dengue virus (DENV), a single-stranded RNA virus consisted of four serotypes. Central nervus system (CNS) impairment in dengue usually results from DENV-2 or DENV-3 infection, which lead to life-threatening outcomes. Furthermore, neurological complications due to DENV-1 was rare especially in adult patients.
METHODS: A 44-year-old man without comorbidities had lethargy after hyperpyrexia and a positive DENV NS1 antigen was detected for confirming the diagnosis of dengue on day 8 of onset. Then logagnosia, decreased muscle strength, delirium and irritability were occurred even radiographic examination were normal. He was treated with low-dose hormone, sedatives and gamma goblin with a short duration of 6 days. The cerebrospinal fluid (CSF) tests were persistent normal. However, presence of DENV-1 RNA was confirmed both in CSF and serum. Furthermore, the complete sequence of the DENV isolated from the patient\'s serum was performed (GenBank No.: MW261838). The cytokines as IL-6, IL-10 and sVCAM-1 were increased in critical phase of disease. Finally, the patient was discharged on day 24 of onset without any neurological sequelae.
CONCLUSIONS: Encephalopathy caused by a direct CNS invasion due to DENV-1 during viremia was described in an adult patient. Treatment with low-dose hormone and gamma goblin was helpful for admission.

UNASSIGNED: Immune-related adverse effects (irAEs) often occur during immune checkpoint inhibitor (ICI) therapy. In the nervous system, the incidence of irAEs ranges from 0.1-12%, with 80% occurring within the first 4 months of ICI application. For complications of the nervous system, adequate diagnosis is made by signs, symptoms, imaging and cerebrospinal fluid. If severe irAEs occur, ICIs should be discontinued and patients should be treated with high-dose glucocorticoids, immunoglobulins, or immunosorbent therapy with systemic support. Patients who develop severe neurologic irAEs have a poorer prognosis.
UNASSIGNED: In this article, we report 2 cases of encephalopathy induced by anti-programmed cell death protein 1 (PD-1) monoclonal antibodies at the initial diagnoses. Our findings may help clinicians to differentiate between encephalopathy caused by immunotherapy and other neurological disorders. Case 1 was a 24-year-old male patient who had undergone PD-1 immunotherapy to treat olfactory neuroblastoma. After the 6th course of therapy, he began to develop persistent epilepsy, which decreased significantly after high doses of glucocorticoid and immunosorbent therapy were administered. Based on his medical history and laboratory examination results, PD-1-induced encephalopathy was the most likely diagnosis. Case 2 was a 67-year-old female patient who had been treated with PD-1/programmed death ligand-1 therapy for lung adenocarcinoma. She began to have headaches after 1 cycle of treatment, and her cognitive function gradually decreased with the continuation of immunotherapy.
UNASSIGNED: These case reports show the difficulty in distinguishing PD-1-induced encephalopathy from other neurological disorders, especially paraneoplastic neurological syndromes. If not treated properly, patients\' lives may be endangered. Thus, early identification and early treatment are very important.