The search for therapeutic targets for Parkinson's disease (PD) is hindered by the incomplete understanding of the pathophysiology of the disease. Mitochondrial dysfunction is an area with high potential. The neurobiological signaling connections between the gut microbiome and the central nervous system are incompletely understood. Multiple lines of evidence suggest that the gut microbiota participates in the pathogenesis of PD. Gut microbial dysbiosis may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The intervention of gut microbial metabolites via the microbiota-gut-brain axis may serve as a promising therapeutic strategy for PD. In this narrative review, we summarize the potential roles of gut microbial dysbiosis in PD, with emphasis on microbial metabolites and mitochondrial function. We then review the possible ways in which microbial metabolites affect the central nervous system, as well as the impact of microbial metabolites on mitochondrial dysfunction. We finally discuss the possibility of gut microbiota as a therapeutic target for PD.

The microbiota-gut-brain axis has emerged as a focal point of biomedical research. Alterations of gut microbiota are involved in not only various immune/inflammatory disorders but also neurological disorders including Alzheimer's disease (AD). The initial stage of the involvement of gut microbiota in the pathogenesis of AD may be the dysfunction of the blood-brain barrier (BBB). Gut microbiota-derived products in the circulation can worsen the BBB integrity, easily cross the disrupted BBB and enter the brain to promote pathological changes in AD. In this review, we first summarize the current evidence of the associations among gut microbiota, AD, and BBB integrity. We then discuss the mechanism of gut microbiota on BBB dysfunction with a focus on bacteria-derived lipopolysaccharide and exosomal high-mobility group box 1. Novel insights into the modification of the BBB as an intervention approach for AD are highlighted as well.

BACKGROUND:Investigations have revealed the association between inflammation and post-stroke depression (PSD). However, whether the C-reactive protein (CRP) level, a biomarker of inflammation, would affect the development of PSD is still controversial. METHODS:A systematic search of databases was performed for eligible studies. Standardized Mean Difference (SMD) with 95 % Confidence Interval (CI) was used to assess the association between the CRP level in the acute phase of stroke and the risk of PSD. RESULTS:13 cohort studies that involved 3536 participants were included. Combined results showed that compared with non-PSD patients, the CRP level of PSD patients was significantly higher on admission (SMD = 0.19, 95 % CI: 0.12-0.27). A subgroup analysis by classifying the assessment time of depression showed obvious differences of the CRP levels between the PSD patients who were diagnosed more than 1 month after stroke and the non-PSD (1-3 months: SMD = 0.16, 95 % CI: 0.06-0.25; >3months: SMD = 0.34, 95 % CI: 0.18-0.51). CONCLUSION:A higher level of CRP in the acute phase of stroke suggests an increased risk for PSD.

Immunoglobulin G4 (IgG4)-related disease is a systemic disease characterized by sclerosing lesions and an increased serum IgG4 level. This condition can involve any organ, but IgG4-related spinal pachymeningitis is relatively rare. In the current study, we report a case of spinal cord compression caused by IgG4-related spinal pachymeningitis. A 39-year-old man presented to us with a 15-day history of back pain and a 3-day history of dysuresia, exacerbated by weakness in the lower extremities for 2 days. Cervical magnetic resonance imaging (MRI) showed strip-shaped abnormal signals along the anterior and posterior borders of the spinal cord at the C5-T4 levels. The IgG level in cerebrospinal fluid was 718.0 mg/L. Thoracic MRI revealed strip-shaped abnormal signals with remarkable enhancement along the anterior and posterior borders of the dural sac at the T1-T6 levels. Histopathological examination confirmed IgG4-related spinal pachymeningitis. The symptoms worsened rapidly, and surgical resection of the space-occupying lesion in the vertebral canal was performed for spinal decompression. Corticosteroid therapy was administered, and the patient's motor functions were mildly improved. IgG4-related disease can manifest as spinal pachymeningitis and cause spinal cord compression. Clinicians should be aware of this rare condition, and early diagnosis, timely surgical decompression, and appropriate corticosteroid therapy should be highlighted.

To explore the short-term efficacy and tolerability of paroxetine in the treatment of panic disorder in adults.Multiple electronic databases were searched to find randomized controlled trials (RCTs) on paroxetine and panic disorder. The primary efficacy outcomes were: the mean change compared to the baseline in the total number of full panic attacks, Clinical Global Impression-Severity of Illness (CGI-S) score, and the proportion of participants with zero full panic attacks and with a 50% or greater reduction in the number of full panic attacks. The tolerability outcomes included withdrawal rate and the incidence of adverse events (AEs).13RCTs were included. The pooled analyses showed patients who received paroxetine experienced greater improvements in the number of full panic attacks (total: MD=-1.96, 95%CI -3.45 to -0.47, P=0.010; ≥50% reduction: OR=1.66, 95%CI 1.08 to 2.55, P=0.02; zero full panic attacks: OR=1.70, 95%CI 1.42 to 2.03, P < 0.00001) and CGI-S (MD=-0.37, 95%CI -0.74 to -0.01, P=0.05) than placebo. There was no evident difference in the total withdrawal rate (OR=0.91, 95%CI 0.76 to 1.08, P=0.26) and withdrawal rate due to AEs (OR=1.29, 95%CI 0.97 to 1.72, P=0.07) between the two groups. Withdrawal rate due to lack of efficacy or relapse (OR=0.44, 95%CI 0.31 to 0.63, P < 0.00001) and the incidence of serious AEs (OR=0.42, 95%CI 0.23 to 0.79, P=0.007) in the paroxetine group was lower than the placebo group. Meanwhile, the incidence of any treatment-emergent adverse events (TEAEs) (OR=1.32, 95%CI 1.05 to 1.64, P=0.02) in the paroxetine group was higher in comparison with the placebo.Paroxetine is an effective and well-tolerated short-term treatment for adults with panic disorder.

Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term “microbiota-gut-brain axis” from “gut-brain axis” underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer’s disease (AD). Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.

Objective To explore the short-term efficacy and tolerability of paroxetine in the treatment of panic disorder in adults. Methods Multiple electronic databases were searched to find randomized controlled trials (RCTs) on paroxetine and panic disorder. The primary efficacy outcomes were: the mean change compared to the baseline in the total number of full panic attacks, Clinical Global Impression-Severity of Illness (CGI-S) score, and the proportion of participants with zero full panic attacks and with a 50% or greater reduction in the number of full panic attacks. The tolerability outcomes included withdrawal rate and the incidence of adverse events (AEs). Results 13RCTs were included. The pooled analyses showed patients who received paroxetine experienced greater improvements in the number of full panic attacks (total: MD=-1.96, 95%CI -3.45 to -0.47, P=0.010; >= 50% reduction: OR=1.66, 95%CI 1.08 to 2.55, P=0.02; zero full panic attacks: OR=1.70, 95%CI 1.42 to 2.03, P < 0.00001) and CGI-S (MD=-0.37, 95%CI -0.74 to -0.01, P=0.05) than placebo. There was no evident difference in the total withdrawal rate (OR=0.91, 95%CI 0.76 to 1.08, P=0.26) and withdrawal rate due to AEs (OR=1.29, 95%CI 0.97 to 1.72, P=0.07) between the two groups. Withdrawal rate due to lack of efficacy or relapse (OR=0.44, 95%CI 0.31 to 0.63, P < 0.00001) and the incidence of serious AEs (OR=0.42, 95%CI 0.23 to 0.79, P=0.007) in the paroxetine group was lower than the placebo group. Meanwhile, the incidence of any treatment-emergent adverse events (TEAEs) (OR=1.32, 95%CI 1.05 to 1.64, P=0.02) in the paroxetine group was higher in comparison with the placebo. Conclusions Paroxetine is an effective and well-tolerated short-term treatment for adults with panic disorder.

Toxoplasmosis is a worldwide zoonosis caused by an intracellular protozoan parasite, Toxoplasma gondii. We report here a diabetic patient who was diagnosed as toxoplasmosis with multiple cranial nerve palsies and cavernous sinusitis. A 37-year-old male presented with an 11-day history of gingival pain, one day history of ptosis and diplopia. He has been having diabetes mellitus for 6 years, and has a history of contact with cats. After admission, his symptoms worsened with right 3rd to 7th cranial nerve palsies. The brain magnetic resonance imaging (MRI) showed cavernous sinusitis in the right sellar region. Serology for toxoplasma was positive for IgM and negative IgG. The patient was treated with oral clindamycin (900 mg/day) and dexamethasone (15 mg/day). The right visual acuity and lid-conjunctival swelling improved after 3 days. At follow-up after a month, the movement of the right eye significantly improved. This case demonstrate the rare occurrence of multiple cranial nerve (3rd to 7th) palsies from toxoplasmosis cavernous sinusitis, which is a potentially treatable condition.

Post-stroke depression often seriously affects the prognosis and quality of life of patients and many clinical trials had shown that Chai Hu Shu Gan San combined with selective serotonin reuptake inhibitors (SSRIs) had good efficacy and minor side effects. We aimed to conduct this meta-analysis to evaluate the efficacy and safety of Chai Hu Shu Gan San as an adjuvant drug for SSRI in treating post-stroke depression. We searched PubMed, EMBASE, Cochrane Library, Wanfang, China Biology Medicine disc (CBM), Chongqing VIP, and CNKI (China National Knowledge Infrastructure) from their date of foundation to December 15, 2018. Literature screening, data extraction and quality assessment were conducted by two authors independently. The data synthesis and analysis were performed by using Review Manager (RevMan) 5.3 software and sensitivity analysis was conducted to assess the robustness of the results. Finally, a total of 22 articles were included. The meta-analysis confirmed the advantages of the combination of SSRI and Chai Hu Shu Gan San, mainly from four aspects: the Hamilton Depression (HAMD) scale score (MD=3.66; 95% DI=2.33-4.98; p<0.001), the Modified Edinburgh Scandinavian Stroke Scale (MESSS) score (MD=4.87; 95% CI=2.32-7.43; p<0.001), the efficacy rate (OR=3.50; 95% CI=2.61-4.69; p<0.001) and the incidence of adverse reactions (OR=0.28; 95% CI=0.17-0.46; p<0.001). No significant publication bias was observed, and sensitivity analysis suggested a good stability of the results. According to the present evidence, we concluded that Chai Hu Shu Gan San in combination with SSRI may be effective and safe in the treatment of post-stroke depression.

OBJECTIVE: Cerebral small vessel diseases (CSVDs) are common causes of cognitive impairments and mood disorders. In recent years, event-related potential P300 has received increasing attention as a biomarker of cognitive impairments or mood disorders. Previous studies on P300 mainly focused on anxiety, depression or cognitive impairments, and few results have been reported on P300 in CSVD patients. The present study aimed to explore the relationship between neuropsychological test scores and P300 in patients with CSVDs. METHODS: The clinical data of 52 patients with CSVDs admitted to the Neurology ward of the First Hospital of Jilin University from June 2016 to October 2017 were collected. All patients who met the inclusion criteria were assessed by both cognitive tests and mood scales within 1 week after enrollment, followed by measurement of P300. Accordingly, patients were assigned to the following four groups: cognitive impairment, non-cognitive impairment, mood disorder, and non-mood disorder.The amplitude and latency values of P300 were measured from the Pz, Fz, Fpz, C3, C4 and Cz electrode sites. In addition, correlations of P300 responses and neuropsychological test scores were analyzed. RESULTS: Significant differences were found in the P300 latency values between the cognitive impairment group and non-cognitive impairment group (P<0.05). P300 latency values were more significantly prolonged in the mood disorder group at the Fz, C3 and Cz electrode sites than in the non-mood disorder group. Positive correlations were found between Hamilton Depression Scale scores and C3, Fz and Cz latencies. Females tended to have a statistically higher risk of emotional impairment than did males (p<0.05). CONCLUSION: P300 latency values can be used as a objective indicator of cognitive impairments and mood disorders in CSVD patients.

In this report, we describe a woman patient who presented with general fatigue and gradual weakness of the limbs. Her husband was diagnosed with syphilis. We performed a serological examination for syphilis and muscle biopsy. Her serological examination was TPPA (treponema pallidum particle agglutination assay)-positive and RPR (rapid plasma reagin)-positive with a titer of 1:16. Muscle biopsy showed abnormal lipid accumulation in myofibers. The genetic test revealed homozygous mutation at c. 770A > G (p.Y257C) of the ETFDH (electron transferring-flavoprotein dehydrogenase) gene. We conclude that this woman was infected with syphilis from her husband, and because she was a c.770A > G ETFDH mutant, multiple acyl-CoA dehydrogenase deficiency (MADD) was triggered.

We report a case of a 51-year-old man with limbic encephalitis (LE) associated with antibodies against the α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic acid receptor (AMPAR). The patient presented with anterograde memory loss for 2 months. Cranial magnetic resonance and electroencephalogram were normal. AMPAR antibodies were found in blood serum and cerebrospinal fluid. All other test results were unremarkable. CT scans found a tumor in the right lobus superior pulmonis. A CT-guided needle biopsy was performed and pathological results showed small cell lung cancer (SCLC). The patient was diagnosed with LE associated with AMPAR antibodies and SCLC. Three months after immunotherapy and tumor removal, patient's memory was partially restored. We recommend that AMPAR antibodies should be detected in patients with classic LE with or without tumor. Prompt treatment of the tumor and immunotherapy are important.

Epilepsy is a brain and neurological disorder with high prevalence. It was reported that more than 70% of epileptic seizures were controlled by anti-epileptic medications, whereas the lack of evidence with respect to head-to-head comparisons motivated researchers to seek alternative approaches that are able to provide deep insights into the profile of anti-epileptic medications. In this study, we performed a network meta-analysis (NMA) to evaluate the efficacy and safety of anti-epileptic medications for partial seizures of epilepsy. Publications were retrieved from PubMed, Embase, and Cochrane Library. Then, studies were screened and selected based on the inclusion criteria. Data were extracted and a NMA was performed to combine both direct and indirect evidence. Surface under the cumulative ranking curve (SUCRA) was obtained for ranking purposes. Consistency between direct and indirect evidence was assessed by using the node-splitting method. Seventeen anti-epileptic medications from 90 publications were enrolled. Fifty percent responder and state of seizure freedom were studied as outcomes for efficacy; treatment emergent adverse effect (TEAE), including dizziness, somnolence, headache, fatigue, and nausea were evaluated as safety outcomes. Topiramate, levetiracetam, pregabalin, and oxcarbazepine were recommended for their relatively high efficacy and low-risk of adverse events for partial seizures. Rufinamide was the least preferable medication due to its low efficacy and high-risk of adverse effects. J. Cell. Biochem. 118: 2850–2864, 2017. © 2017 Wiley Periodicals, Inc.

Objective To investigate whether edaravone jointed PDTC can inhibit inflammatory response mediated by the MCP-1 to reduce the cognitive impairment caused by chronic ischemia in rats.Methods Choose 60 male Wistar rats and divided into model group,drug intervention group 1,drug intervention group 2,drug intervention group 3 and the control group randomly.Applicated the permanent ligation bilateral common carotid arteries method (2VO)to pre-pare the chronic forebrain ischemia animal model of vascular dementia.Postoperative,intraperitoneal injected PDTC, edaravone and edaravone jointed PDTC into drug intervention group rats respectively.Using Morris water maze on each group rats in before and after operation to measure the escape latency to response the cognitve function.Used of ELISA to measure the MCP-1 expression in brain of every group.Results Compared the escape latency time of drug interven-tion group1,2,3 and model rats respectively compared with control group with control group after model building 60 days,differences were significant;Drug intervention group 1 and 3,respectively,compared with model group,differences were significant.The MCP-1 concentration of control group,model group,drug intervention group 1,2,3 detected by ELISA was (1.58±0.21)ng/mL、(8.15±1.92)ng/mL、(5.12±1.13)ng/mL、(7.02±1.83)ng/mL、(2.96±0.56) ng/mL respectively.Drug intervention group1,3,respectively,compared with model group was 2.256,4.127,differ-ences were significant(P <0.05);Drug intervention group 3,respectively,compared with drug intervention group1,2,t was 1.974and 3.562 respectively,differences were significant(P <0.05).Conclusion Edaravone jointed PDTC can in-hibit the expression of MCP-1 so that to inhibit the inflammatory response indirectly mediated by the MCP- 1,so can protect the learning and memory function of vascular dementia rats.

We report a case of histopathologically-confirmed primary central nervous system lymphoma who was initially diagnosed as demyelinating encephalopathy. A 58-year-old woman was admitted with confusion and left hemiparesis. Head MR showed abnormal flaky hypointense T1 and hyperintense T2 signals at right thalamus, splenium of corpus callosum, bilateral cerebral peduncle, pons, medulla oblongata, basal ganglia and right corona radiata. Her mental status improved a little and she was discharged from hospital after neuroprotective treatment. 10 days after her discharge, her confusion appeared again with hallucination and unsteady walking. Pathological examination revealed non-Hodgkin's lymphoma (WHO classification: DLBCL). The patient continued to deteriorate after the surgery and died 10 days later.

Oligoastrocytoma (OA) is an extremely rare tumor that may be difficult to diagnose, as it mimics multiple sclerosis (MS) clinically and radiologically. OA and MS are both space-occupying lesions. The symptoms of OA are complex and depend on tumor location and size. The clinical symptoms of OA are frequently not typical of glioma; therefore, OA is associated with a high misdiagnosis rate. We herein share our experience with diagnosing a rare OA case with atypical symptoms, which was initially diagnosed as MS, while stereotactic biopsy provided the final diagnosis. Due to the rarity and high misdiagnosis rate of OAs, it is suggested that clinical physicians update their knowledge regarding brain tumor classification and increase their awareness of rare tumor occurrence.

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目的 探讨养血清脑颗粒对脑梗死患者颈动脉内-中膜厚度以及动脉粥样硬化斑块大小的影响,以及养血清脑颗粒对脑梗死患者的二级预防作用机制.方法 将100例脑梗死患者随机分成两组.第1组为对照组,给予常规抗血小板聚集,改善循环,营养神经等对症治疗,住院治疗2 w后,只给予口服拜阿司匹林6 m.第2组为治疗组,除给予上述常规治疗外,同时给予养血清脑颗粒4 g,每日3次口服,住院治疗2w后,继续口服拜阿司匹林加养血清脑颗粒6 m.6 m后测量患者颈动脉内-中膜厚度及动脉粥样硬化斑块大小以及检测血常规、凝血常规、血脂、血糖、血液粘度.对两组患者数据进行统计学分析.结果 对照组50例患者6 m后随诊复查,颈部彩超显示斑块面积缩小7例,无明显改变者20例,斑块面积增大者23例.治疗组50例患者颈部彩超显示斑块面积缩小25例,无明显改变者16例,斑块面积增大者9例.治疗组患者,颈动脉内膜的动脉粥样硬化斑块面积治疗前后比较均有明显缩小,有显著性差异(P＜0.01).而对照组患者治疗前后斑块面积无明显改变,无显著性差异(P＞0.05).结论 养血清脑颗粒可改善脑梗死患者的颈动脉内-中膜厚度,对脑梗死患者的二级预防有一定价值.

Grosso et al. 1 Grosso S. Verrotti A. Tei M. Cornacchione S. Giannini F. Balestri P. Recurrent Miller Fisher syndrome in children. Pediatr Neurol. 2014; 50: 269-271 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar reported two patients with recurrent Miller Fisher syndrome. This adds to the literature in terms of the clinical features of pediatric Miller Fisher syndrome. Miller Fisher syndrome, a clinical syndrome characterized by a triad of ataxia, areflexia, and ophthalmoplegia, was first described by C. Miller Fisher in 1956. 2 Fisher M. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med. 1956; 255: 57-65 Crossref PubMed Scopus (859) Google Scholar Miller Fisher syndrome has been classified as a subtype of Guillain-Barré syndrome, an immune-mediated disorder in the peripheral nervous system associated with hyporeflexia or areflexia. Miller Fisher syndrome can recur. 3 Heckmann J.G. Dütsch M. Recurrent Miller Fisher syndrome: clinical and laboratory features. Eur J Neurol. 2012; 19: 944-954 Crossref PubMed Scopus (28) Google Scholar Although rare, recurrent pediatric Miller Fisher syndrome has been documented. 4 Hamaguchi T. Yamaguchi K. Komai K. et al. Recurrent anti-GQ1b IgG antibody syndrome showing different phenotypes in different periods. J Neurol Neurosurg Psychiatry. 2003; 74: 1350 Crossref PubMed Scopus (23) Google Scholar While Miller Fisher syndrome that occurs in the absence of the typical triad without limb weakness can be easily recognized, cases with significant motor deficit are considered to be Guillain-Barré syndrome–Miller Fisher syndrome overlap syndrome. 5 Sejvar J.J. Kohl K.S. Gidudu J. et al. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011; 29: 599-612 Crossref PubMed Scopus (372) Google Scholar Recurrent Miller Fisher Syndrome in ChildrenPediatric NeurologyVol. 50Issue 3PreviewMiller Fisher syndrome is usually a monophasic disorder. Recurrent Miller Fisher syndrome is extremely rare, and all patients with recurrences have been adults. Although the optimal treatment for Miller Fisher syndrome has yet to be established, the typical therapy includes intravenous immunoglobulin or plasma exchange. The efficacy of steroids is still debated. Full-Text PDF