Development of a model to predict the risk of cerebral infarction in acute vestibular syndrome.

Objectives: This study aimed to develop a model to predict the risk of cerebral infarction in acute vestibular syndrome and assist emergency physicians in quickly identifying patients with cerebral infarction. Materials and methods: We looked at 262 patients who were split into cerebral infarction and peripheral vertigo groups. Stepwise regression and Lasso's approach were used to screen for variables, and Boothstrap's method was used to evaluate the model's discrimination and calibration. The model's performance was compared against TriAGe+, ABCD2, and PCI scores using the area under the receiver operator characteristic curve. Clinical decision-making was aided by the use of clinical impact and decision curves. Results: In the end, nine risk factors were chosen for model 2, and ten risk factors were chosen for model 1. Model 2 was adopted as the final model. The areas under the receiver operator curve value of the model2 were 0.910(P = 0.000), much higher than the areas under the receiver operator curve value of the TriAGe + scores system and that of the PCI scores system. The clinical decision curve shows that when the threshold probability is 0.05, using the nomogram to predict cerebral infarction has more benefits than either the treat-all-patients scheme or the treat-none scheme. The clinical impact curve shows that when the threshold probability is 0.6 the model predicts disease occurrence in general agreement with the occurrence of the real disease. Conclusion: This study model can help emergency room physicians quickly triage and treat patients by accurately identifying cerebral infarction patients.

A decision support system for primary headache developed through machine learning.

BACKGROUND: Primary headache is a disorder with a high incidence and low diagnostic accuracy; the incidence of migraine and tension-type headache ranks first among primary headaches. Artificial intelligence (AI) decision support systems have shown great potential in the medical field. Therefore, we attempt to use machine learning to build a clinical decision-making system for primary headaches. METHODS: The demographic data and headache characteristics of 173 patients were collected by questionnaires. Decision tree, random forest, gradient boosting algorithm and support vector machine (SVM) models were used to construct a discriminant model and a confusion matrix was used to calculate the evaluation indicators of the models. Furthermore, we have carried out feature selection through univariate statistical analysis and machine learning. RESULTS: In the models, the accuracy, F1 score were calculated through the confusion matrix. The logistic regression model has the best discrimination effect, with the accuracy reaching 0.84 and the area under the ROC curve also being the largest at 0.90. Furthermore, we identified the most important factors for distinguishing the two disorders through statistical analysis and machine learning: nausea/vomiting and photophobia/phonophobia. These two factors represent potential independent factors for the identification of migraines and tension-type headaches, with the accuracy reaching 0.74 and the area under the ROC curve being at 0.74. CONCLUSIONS: Applying machine learning to the decision-making system for primary headaches can achieve a high diagnostic accuracy. Among them, the discrimination effect obtained by the integrated algorithm is significantly better than that of a single learner. Second, nausea/vomiting, photophobia/phonophobia may be the most important factors for distinguishing migraine from tension-type headaches.

NIHSS-the Alberta Stroke Program Early CT Score mismatch in guiding thrombolysis in patients with acute ischemic stroke.

OBJECTIVE: This study investigates the mismatch between the National Institutes of Health Stroke Scale (NIHSS) score and the computed tomography (CT) findings measured by the Alberta Stroke Program Early CT Score (ASPECTS) for predicting the functional outcome and safety of intravenous thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS). METHODS: This prospective observational study includes patients with AIS who underwent CT imaging within 4.5 h of the onset of symptoms. Patients were divided into the NIHSS-ASPECTS mismatch (NAM)-positive and NAM-negative groups (group P and N, respectively). The clinical outcome was assessed using the Modified Rankin Scale (mRS). Safety outcomes included progression, symptomatic intracerebral hemorrhage (sICH), intracerebral hemorrhage (ICH), adverse events, clinical adverse events, and mortality. RESULTS: A total of 208 patients were enrolled in the study. In group P, IVT treatment was associated with a good functional outcome at 3 months (p = 0.005) and 1 year (p = 0.001). A higher percentage of patients with favorable mRS (0-2) (p = 0.01) and excellent mRS (0-1) (p = 0.011) functional outcomes was obtained at 1 year in group P with IVT treatment. Group N did not benefit from the same treatment (p = 0.352 and p = 0.480 at 3 months and 1 year, respectively). There were no statistically significant differences in sICH, ICH, mortality rates, or other risks between the IVT and conventional treatment groups. CONCLUSION: IVT treatment is associated with a good functional outcome in patients with NAM, without increasing the risks of sICH, ICH, mortality, or other negative outcomes. NAM promises to be an easily obtained indicator for guiding the treatment decisions of AIS.

Effect of platelet count on long-term prognosis of cerebral infarction.

OBJECTIVE: This study aimed to analyze the correlation between platelet (PLT) count and the modified Rankin scale (mRS) in patients with cerebral infarction (CI) at the later stage of rehabilitation, which can be used to guide the secondary prevention strategy of CI. METHODS: A total of 180 CI patients were divided into three groups according to PLT count: low PLT group (<125×109/L), medium PLT group (126- 225×109/L) and high PLT group (>226×109/L). The mRS was evaluated after three months and one year, respectively, and the difference in long-term prognosis between groups was analyzed. The mRS is an ordered scale coded from 0 (no symptoms at all) through 5 (severe disability) 6 (death). RESULTS: Finally, a total of 99 patients had complete data. The results of the multiple comparisons among the three groups were as follows: the analysis of variance of the mRS at three months after onset yielded F = 6.714 and P = 0.002, and the difference was statistically significant. The mRS was lowest in the medium PLT group (2.09±1.465), and neurological function recovery was the best. After one year, the mRS for the medium PLT group was the lowest (1.49±1.523), with F = 6.860 and P = 0.002. The repeated measures analysis of variance revealed that the effect of continuous rehabilitation was significant in the interval from three months to one year after onset (F = 35.528, P < 0.001). This was very significant, especially for patients taking aspirin (F = 50.908, P < 0.001). However, for patients who did not take aspirin, the effect of continuous rehabilitation was not obvious during the nine months, and the difference between the results of two mRS measurements was not statistically significant (F = 1.089, P = 0.308). CONCLUSIONS: Patients with a PLT count of 126- 225×109/L had the lowest mRS between three months and one year after onset, but had the best recovery of nerve function. Patients who persisted in taking aspirin continued to significantly recover during the 9-month period, from three months to one year after onset. Aspirin is not only a secondary preventive drug, but also an important drug to promote the rehabilitation of CI patients.

Identification of potential crucial genes and molecular mechanisms in glioblastoma multiforme by bioinformatics analysis.

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor of the adult central nervous system and is associated with poor prognosis. The present study aimed to identify the hub genes in GBM in order to improve the current understanding of the underlying mechanism of GBM. The RNA­seq data were downloaded from The Cancer Genome Atlas database. The edgeR package in R software was used to identify differentially expressed genes (DEGs) between two groups: Glioblastoma samples and normal brain samples. Gene Ontology (GO) functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed using Database for Annotation, Visualization and Integrated Discovery software. Additionally, Cytoscape and Search Tool for the Retrieval of Interacting Genes/Proteins tools were used for the protein­protein interaction network, while the highly connected modules were extracted from this network using the Minimal Common Oncology Data Elements plugin. Next, the prognostic significance of the candidate hub genes was analyzed using UALCAN. In addition, the identified hub genes were verified by reverse transcription­quantitative (RT­q) PCR. In total, 1,483 DEGs were identified between GBM and control samples, including 954 upregulated genes and 529 downregulated genes (P<0.01; fold­change >16) and these genes were involved in different GO terms and signaling pathways. Furthermore, CDK1, BUB1, BUB1B, CENPA and GNG3 were identified as key genes in the GBM samples. The UALCAN tool verified that higher expression level of CENPA was relevant to poorer overall survival rates. In conclusion, CDK1, BUB1, BUB1B, CENPA and GNG3 were found to be potential biomarkers for GBM. Additionally, 'cell cycle' and 'γ­aminobutyric acid signaling' pathways may serve a significant role in the pathogenesis of GBM.

r-tPA with loading dose of clopidogrel and aspirin therapies for capsular warning syndrome attributed to middle cerebral artery atherosclerotic stenosis: A CARE-compliant case report.

RATIONALE: The capsular warning syndrome (CWS) is a rare and special type of transient ischemic attacks (TIAs) syndrome. The pathophysiology of CWS is very complicate, and intracranial atherosclerotic stenosis (ICAS) is rare cause. Moreover, the effective and standard therapy has not yet been established. PATIENT CONCERNS: A 47-year-old man experienced repeated and exacerbated TIAs of right hemiparesis and dysarthria. Fourteen hours after the first episode of TIAs, he developed more severe right hemiparesis and dysarthria, the National Institute of Health Stroke Scale (NIHSS) score was 12 points, and did not recover in a long time. DIAGNOSIS: The computed tomography (CT) angiography displayed high stenosis in the M1 segment of the left middle cerebral artery. The patient was diagnosed as CWS with ICAS. INTERVENTIONS: Loading dose of clopidogrel and aspirin were started but were ineffective, then we used recombinant tissue plasminogen (r-tPA) for thrombolysis therapy after repeat CT scan that showed small acute infarcts in the right putamen and no bleeding. OUTCOMES: The patient was successfully treated by r-tPA intravenous thrombolysis after loading dose of dual-anti-platelet. He recovered rapidly, and the NIHSS score was 0 point, modified Rankin Scale score was 0 point, and Barthel Index score was 100 points at 3-month follow-up. LESSONS: r-tPA combined with loading dose of dual antiplatelet appears safe and effective in carefully selected CWS patients with ICAS. The collection of similar cases and further randomized controlled trial research would be desirable.

Inhibition of USP15 Prevent Glutamate-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway in HT22 Cells.

Oxidative stress has been identified as the significant mediator in epilepsy, which is a chronic disorder in central nervous system. About 30% of epilepsy patients are refractory to antiepileptic drug treatment. However, the underlying mechanism of oxidative damage in epilepsy needs further investigation. In our study, we first find that ubiquitin-specific peptidase 15 (USP15) expression was upregulated in a pentylenetetrazole (PTZ) kindled rat model of epilepsy. Silencing USP15 protected against glutamate-mediated neuronal cell death, and inhibited the high expression levels of cleaved caspase-3. Knockout of USP15 significantly reduced intracellular reactive oxygen species (ROS) levels and enhanced superoxide dismutase (SOD) activity in HT22 cells under the exposure to glutamate treatment. Furthermore, USP15 inhibition induced nuclear factor erythroid-derived 2-related factor2 (Nrf2) nuclear translocation and promoted protein expression level of heme oxygenase (HO-1). Taken together, our findings first reveal a role of USP15 in the pathogenesis of epilepsy, and silencing USP15 in vitro protects against glutamate-mediated cytotoxicity in HT22 cells. Pharmacological inhibition of USP15 may alleviate epileptic seizures via fighting against oxidative damage, providing a novel antiepileptic target.

Higher Platelet-to-Lymphocyte Ratio Is Associated With Worse Outcomes After Intravenous Thrombolysis in Acute Ischaemic Stroke.

Objective: The platelet-to-lymphocyte ratio (PLR) is a new marker of atherosclerotic inflammation and has been identified as a predictive factor in cardiovascular diseases, but its significance in patients with acute ischaemic stroke (AIS) who have undergone intravenous thrombolysis (IVT) is still unknown. Methods: Consecutive patients who were treated with IVT using recombinant tissue plasminogen activator (rtPA) for AIS were included from May 2012 to August 2018. The PLR was calculated according to platelet and lymphocyte counts within 24 h after thrombolysis therapy. Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months after thrombolysis. Stroke severity was assessed by National Institutes of Health Stroke Scale (NIHSS) scores. The primary endpoint was an unfavorable outcome (mRS > 2), and the secondary endpoint was death at 3 months. Results: A total of 286 patients were included in the study. The median age was 69.5 (59.0-80.0) years, and 59.1% of patients were men. A total of 120 (42.0%) patients had an unfavorable outcome, and 38 (13.2%) died. Patients with an unfavorable outcome had significantly higher PLR values compared with those with a favorable outcome [172.5 (105.3-239.0) vs. 139 (97.0-194.5), P = 0.008], and the PLR values of the patients who died at 3 months were higher than those of the surviving patients [189.5 (127.5-289.0) vs. 142.0 (98.0-215.5), P = 0.006]. After adjustment for other variables, the PLR was independently associated with the two endpoints: unfavorable outcome (OR 2.220, 95% CI 1.245-3.957, P = 0.007) and death (OR 2.825, 95% CI 1.050-7.601, P = 0.040) at 3 months after thrombolysis. In addition, PLR was correlated with the NIHSS score (R = 0.230, P < 0.001). Conclusions: Higher PLR levels were independently associated with an unfavorable outcome and death at 3 months in AIS patients treated with IVT.

Effect of topiramate on interleukin 6 expression in the hippocampus of amygdala-kindled epileptic rats.

The objective of this study was to analyze the changes in expression and the possible functions of interleukin-6 (IL-6) in electrical kindling of the basolateral amygdala (BLA) in epileptic rats. Bipolar electrodes were implanted into the BLA of Sprague-Dawley rats, and the rats were then subjected to chronic electrical stimulation through the electrodes to induce kindling. The seizure characteristics and behavioral changes of the rats were observed, and electroencephalograms were recorded during and following kindling. The IL-6 mRNA expression in the hippocampi of the rats was analyzed using semi-quantitative reverse transcription-polymerase chain reaction, and control and topiramate (TPM)-treated groups were compared. The mean time-period required for kindling was 13.50±3.99 days, and the afterdischarge duration (ADD) measured between 21,450 and 119,720 msec. The expression of IL-6 mRNA was significantly upregulated in the kindled rats. TPM was able to depress the seizures and decrease the IL-6 level in the kindled rats. In conclusion, IL-6 mRNA was upregulated in the hippocampi of epileptic rats, and IL-6 may have participated in the process of kindling.

Changes of glucocorticoid receptor mRNA expression in basolateral amygdale-kindled rats.

BACKGROUND: Glucocorticoid receptor (GR) is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is significant change in GR expression under certain pathological state. Epilepsy is a special pathological state of the central nervous system. This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model. METHODS: Firstly, we established the basolateral amygdale-electrical kindled rat epilepsy model. Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment. In addition, the processes of epileptic seizures were observed and electroencephalograms were recorded. One-way analysis of variance (ANOVA) was employed for comparing means of multiple groups, followed Fisher's least significant difference (LSD) for paired comparison. RESULTS: The rats were successfully kindled after an average of (13.50 ± 3.99) times electrical stimulation, in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups (P < 0.001). The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs (P < 0.001 compared with the epilepsy group), accompanied by attenuation of seizures and improvement of electroencephalograms. CONCLUSIONS: Down-regulation of hippocampal GR mRNA expression may be related to the kindling. Anti-epilepsy drugs exposure can retard this change.

Overexpression of human MRP1 in neurons causes resistance to antiepileptic drugs in Drosophila seizure mutants.

Multidrug resistance-associated protein 1 (MRP1), an efflux multidrug transporter, was shown to be elevated in both glia and neurons in seizure focus in refractory epilepsy patients. Up-regulation of MRP1 and other multidrug transporters in perivascular astrocytes was suggested to cause resistance to antiepileptic drugs (AEDs) by reducing the concentration of AEDs at the epileptogenic areas. However, it is not known whether the up-regulation of MRP1 in neurons can cause resistance to AEDs, such as sodium phenytoin (PHT) and valproic acid (VPA). PHT inhibits voltage-gated sodium channel (VGSC) by occluding it, but whether PHT enters the channel through its inner or outer pore is not known. The authors overexpressed human MRP1 protein only in neurons in a Drosophila genetic seizure model, bang senseless (bss) mutants. The authors found that overexpression of MRP1 blocked the attenuation of the seizure behavior of bss mutants by acute and chronic application of PHT, and by chronic application of VPA. Conversely, overexpression of MRP1 in neurons increased the tolerance of bss flies to high-dosage PHT and VPA. Thus, up-regulation of MRP1 expression only in neurons causes resistance to AED in seizure flies. Moreover, the current data suggest that PHT enters VGSC through its inner pore.

The effects of topiramate on caspase-3 expression in hippocampus of basolateral amygdala (BLA) electrical kindled epilepsy rat.

Caspase-3 expression was determined in the hippocampus of electrically kindled rats with and without topiramate treatment. Bipolar electrotrodes were implanted for chronic stimulation of the basolateral amygdala (BLA) to achieve a kindled state. Seizure and behavioral responses were observed, and video-electroencephalograms were recorded during and after kindling. After topiramate treatment (80 mg/kg, p.o.), the hippocampi were extracted and caspase-3 mRNA analyzed by semiquantitative RT-PCR. Caspase-3 immunoreactivity was determined with immunohistochemical staining. Topiramate treatment resulted in a significant decrease in the mean duration of seizures from 52 s in kindled rats to 13 s. The after-discharge duration was significantly decreased by 70% after topiramate treatment. Significant upregulations of both caspase-3 mRNA and caspase-3 immunoreactivity were observed in the kindled rats. These kindling-mediated increases in caspase-3 were prevented by topiramate treatment, and these levels were not different from those of sham-operated controls. In BLA-kindled rats, mRNA and immunoreactivity for caspase-3 were increased. Treatment with topiramate prevented the kindling-associated increases in caspase-3 as well as the increases in seizure duration and after-discharge duration. These data suggest that topiramate may have a neuroprotective role in addition to its action as an anticonvulsant.

Febrile seizures are associated with mutation of seizure-related (SEZ) 6, a brain-specific gene.

Genetic factors contribute significantly to the etiology of febrile seizures (FS), the most common type of seizures in childhood. However, in most patients with FS, the causative gene is unknown. The purpose of this study was to explore the relationship between human brain-specific gene SEZ-6 and FS. Through amplification of genomic DNA by PCR and sequencing of the resulting products, we screened 75 subjects for mutations in the coding region (17 exons) of the SEZ-6 gene. Fifteen subjects were healthy individuals and 60 subjects had FS. Patients with FS could be divided into sub-groups based on seizure type (42 simple and 18 complex) and family history (41 had a positive family history). All patients have been followed to date to evaluate seizure recurrence and the development of epilepsy. No mutations were found in healthy controls, but 21 of the patients with FS had mutations in SEZ-6, and the most common type of mutation was a heterozygous, cytosine insertion (frame shift mutation) at position 1435 of the cDNA. The mutation incidence was significantly higher in patients with complex FS (vs. simple FS) and in patients with a positive family history. Sixteen of 42 patients with simple FS experienced seizure recurrence during the 1-5-year follow-up period. Fifteen of 18 patients with complex FS also experienced a recurrence during this period. Among these patients with recurrences, five patients with simple FS and six patients with complex FS have developed epilepsy. The mutation incidence among these epileptic patients is 72.7%. The human SEZ-6 gene is related to the occurrence and development of FS and may be a novel candidate gene for epilepsy. Screening for mutations in SEZ-6 may be valuable in predicting FS recurrence or the development of epilepsy.