Multi-omics Mendelian randomization integrating GWAS, eQTL and pQTL data revealed GSTM4 as a potential drug target for migraine.

INTRODUCTION: Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. METHOD: We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. RESULT: The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93-0.96); p = 2.70e - 10; Replication cohort: OR(95%CI) = 0.93(0.91-0.94); p = 4.21e - 17). Furthermore, GSTM4 passed the SMR at p < 0.05 and HEIDI test at p > 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87-0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85-0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83-0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. CONCLUSION: This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine.

Association between blood pressure control during aneurysm clipping and functional outcomes in patients with aneurysmal subarachnoid hemorrhage.

Objectives: We explored the relationship between blood pressure variability (BPV) during craniotomy aneurysm clipping and short-term prognosis in patients with aneurysmal subarachnoid hemorrhage to provide a new method to improve prognosis of these patients. Methods: We retrospectively analyzed the differences between patient groups with favorable modified Rankin Scale (mRS ≤ 2) and unfavorable (mRS > 2) prognosis, and examined the association between intraoperative BPV and short-term prognosis. Results: The intraoperative maximum systolic blood pressure (SBPmax, p = 0.005) and the coefficient of variation of diastolic blood pressure (DBPCV, p = 0.029) were significantly higher in the favorable prognosis group. SBPmax (OR 0.88, 95%CI 0.80-0.98) and Neu% (OR 1.22, 95%CI 1.03-1.46) were independent influence factors on prognosis. Patients with higher standard deviations of SBP (82.7% vs. 56.7%; p = 0.030), DBP (82.7% vs. 56.7%; p = 0.030), and DBPCV (82.7% vs. 56.7%; p = 0.030) had more favorable prognosis. Conclusion: Higher SBPmax (≤180 mmHg) during the clipping is an independent protective factor for a 90-day prognosis. These results highlight the importance of blood pressure (BP) control for improved prognosis; higher short-term BPV during clipping may be a precondition for a favorable prognosis.

Joint effect of abnormal systemic immune-inflammation index (SII) levels and diabetes on cognitive function and survival rate: A population-based study from the NHANES 2011-2014.

OBJECTIVE: The purpose of this study was to investigate whether the combination of abnormal systemic immune-inflammation index (SII) levels and hyperglycemia increased the risk of cognitive function decline and reduced survival rate in the United States. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database from 2011-2014 and enrolled 1,447 participants aged 60 years or older. Restricted cubic splines (RCS), linear regression and kaplan-meier(KM) curve were employed to explore the combined effects of abnormal SII and hyperglycemia on cognitive function and survival rate, and subgroup analysis was also conducted. RESULTS: The RCS analysis revealed an inverted U-shaped relationship between lgSII levels and cognitive function. Linear regression analysis indicated that neither abnormal SII nor diabetes alone significantly contributed to the decline in cognitive function compared to participants with normal SII levels and blood glucose. However, when abnormal SII coexisted with diabetes (but not prediabetes), it resulted to a significant decline in cognitive function. After adjusting for various confounding factors, these results remained significant in Delayed Word Recall (ß:-0.76, P<0.05) and Digit Symbol Substitution tests (ß:-5.02, P<0.05). Nevertheless, these results showed marginal significance in Total Word Recall test as well as Animal Fluency test. Among all subgroup analyses performed, participants with both abnormal SII levels and diabetes exhibited the greatest decline in cognitive function compared to those with only diabetes. Furthermore, KM curve demonstrated that the combination of abnormal SII levels and diabetes decreased survival rate among participants. CONCLUSION: The findings suggest that the impact of diabetes on cognitive function/survival rate is correlated with SII levels, indicating that their combination enhances predictive power.

Safety and efficacy of magnesium-rich artificial cerebrospinal fluid for subarachnoid hemorrhage.

Objectives: This study aimed to investigate the efficacy of using a newly formulated magnesium-rich artificial cerebrospinal fluid (MACSF) as an alternative to normal saline (NS) for intraoperative irrigation during aneurysm clipping in improving the prognosis of patients with Aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients with aSAH who underwent intraoperative irrigation with MACSF or NS during the clipping in the First Affiliated Hospital of Xi 'an Jiaotong University from March 2019 to March 2022 were selected as MACSF group and NS group, respectively. The primary prognostic indicators were the incidence of favorable outcomes (mRS 0-2). The secondary outcome measures included cerebral vasospasm (CVS), mortality, total hospital stay, and intensive care unit (ICU) stay. Safety was evaluated based on the occurrence rates of hypermagnesemia, meningitis, and hydrocephalus. Results: Overall, 34 and 37 patients were enrolled in the MACSF and NS groups, respectively. At 90 days after aSAH onset, the proportion of favorable prognosis in the MACSF group was significantly higher than that in the NS group (p = 0.035). The incidence of CVS within 14 days after surgery was significantly lower in the MACSF group than that in the NS group (p = 0.026). The mortality rate in the MACSF group was significantly lower than in the NS group (p = 0.048). The median lengths of hospital stay (p = 0.008) and ICU stay (p = 0.018) were significantly shorter in the MACSF group than in the NS group. No significant differences were observed in safety measures. Conclusion: Using MACSF as an irrigation fluid for aneurysm clipping can significantly improve the 90-day prognosis of patients with aSAH, which may be related to the reduced incidence of CVS. Clinical trial registration: https://www.clinicaltrials.gov, identifier NCT04358445.

The relationship between atrial cardiopathy biomarkers and prognosis of patients with acute ischemic stroke after endovascular treatment.

Thromboembolism is a possible consequence of underlying atrial cardiopathy, which can occur even before the onset of atrial fibrillation. Our objective was to examine the association between biomarkers of atrial cardiopathy and outcomes of acute ischemic stroke (AIS) following endovascular treatment (EVT). We conducted a retrospective study that collected data from patients with AIS who underwent EVT and compared the outcomes between those with and without atrial cardiopathy. Neurological function was assessed using the modified Rankin Scale (mRS), with an mRS score >2 indicating poor function at day 90. Additionally, we evaluated secondary consequences, including symptomatic intracerebral hemorrhage (sICH), early neurological deterioration (END), and malignant cerebral edema (MCE). Our study included 87 patients (77.6 â€‹% male; mean age 60.93 â€‹± â€‹12.47 years). Among these patients, 29 (33.3 â€‹%) had atrial cardiopathy, while the remaining 58 (66.7 â€‹%) did not. In the atrial cardiopathy group, 12 patients (41.4 â€‹%) had poor functional outcomes (mRS>2), compared to 19 (32.8 â€‹%) in the non-atrial cardiopathy group. We observed sICH in 22 (25.3 â€‹%) patients, END in 14 (16.1 â€‹%) patients, MCE in 11 (12.6 â€‹%) patients, and two (2.3 â€‹%) patients who died in the hospital. We found that patients with PTFV1>5000 â€‹µV/ms (OR: 8.39, 95 â€‹% CI: 1.43-105.95, P â€‹= â€‹0.02) and NT-proBNP>250 â€‹pg/mL (OR: 5.09, 95 â€‹% CI: 1.20-27.63, P â€‹= â€‹0.03) had significantly higher risk of END. After adjusting for covariates in the Firth logistic regression, we further found that atrial cardiopathy was significantly associated with END, as revealed by both univariate (OR: 6.31, 95 â€‹% CI: 1.42-59.87, P â€‹= â€‹0.01) and multivariable firth regression models (Modle 1, OR: 7.10, 95 â€‹% CI: 1.57-67.38, P â€‹< â€‹0.01; Modle 2, OR: 7.82, 95 â€‹% CI: 1.69, 76.36, P â€‹< â€‹0.01; Modle 3, OR: 8.59, 95 â€‹% CI: 1.72-91.70, P â€‹< â€‹0.01). Moreover, we observed that atrial cardiopathy was associated with an increased risk of END in AIS patients with large artery atherosclerosis (LAA) receiving EVT. Therefore, clinicians should consider atrial cardiopathy as a possible underlying cause of AIS in their patients. Further investigation is warranted to elucidate the relationship between atrial cardiopathy and AIS's occurrence, progression, and prognosis.

Effects of elevated remnant cholesterol on outcomes of acute ischemic stroke patients receiving mechanical thrombectomy.

OBJECTIVE: Large cohort studies provided evidence that elevated remnant cholesterol (RC) was an important risk factor for ischemic stroke. However, the association between high RC and clinical outcomes in acute ischemic stroke (AIS) individuals was still undetermined. METHODS: This retrospective study enrolled 165 AIS patients undergoing mechanical thrombectomy in one tertiary stroke center. We divided patients into two groups based on the median of their RC levels (0.49 mmol/L). The modified Rankin Scale (mRS) was used to evaluate the primary outcome 90 days after the onset of symptoms. The mRS scores ≤ 2 and ≤ 1 at 90 days were deemed as favorable and excellent outcomes, respectively. RESULTS: In the overall AIS patients undergoing mechanical thrombectomy, there was no obvious distinction between the high and low RC group at 90-day favorable outcome (41.0% vs. 47.1%, P = 0.431) or excellent outcome (23.1% vs. 31.0%, P = 0.252). In the subgroup analysis stratified by stroke etiology, non-large artery atherosclerosis (non-LAA) stroke patients yielded with less favorable or excellent prognosis in the high RC group (26.8% vs. 46.8%, adjusted OR = 0.31, 95%CI: 0.11-0.85, P = 0.023; or 12.2% vs. 29.0%, adjusted OR = 0.18, 95%CI: 0.04-0.80, P = 0.024, respectively.). Post hoc power analyses indicated that the power was sufficient for favorable outcome (80.38%) and excellent outcome (88.72%) in non-LAA stroke patients. Additionally, RC can enhance the risk prediction value of a poor outcome (mRS scores 3-6) based on traditional risk indicators (including age, initial NIHSS score, operative duration, and neutrophil-to-lymphocyte ratio) for non-LAA stroke patients (AUC = 0.86, 95%CI: 0.79-0.94, P < 0.001). CONCLUSION: In AIS patients undergoing mechanical thrombectomy, elevated RC was independently related to poor outcome for non-LAA stroke patients, but not to short-term prognosis of LAA stroke patients.

Remote ischemic postconditioning alleviates cerebral ischemic injury through SERCA2/endoplasmic reticulum stress-mediated apoptosis.

Remote ischemic postconditioning (RIPostC) alleviates brain ischemic injury through several pathways, including endoplasmic reticulum (ER) stress modulation. Sarco endoplasmic reticulum Ca2+ -ATPase(SERCA2) which plays vital role in calcium homeostasis regulation could modulate ER stress logically. This study aimed to investigate whether RIPostC exerts its neuroprotective effect by reducing ER stress mediated by SERCA2. Male SD rats underwent transient middle cerebral artery occlusion (tMCAO) for 2 h followed by reperfusion, with the RIPostC group undergoing 3 cycles of bilateral femoral artery clamping and reperfusion at the beginning of reperfusion. Stroke outcome was assessed based on infarct volume and neurological function evaluation. Protein levels of SERCA2 and other ER stress markers were measured using Western blotting, immunofluorescence, and immunohistochemistry techniques. Compared to the sham group, we observed that RIPostC can effectively reduce cerebral infarct volume after I/R (34.55%: 21.03%; p = .004) and improve neurological function deficit (9.67:12.5; p = .029). Additionally, RIPostC increased SERCA2 protein expression and decreased the protein level of glucose-regulated protein 78 (GRP78), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α) and CCAAT/EBP homologous protein (CHOP). Furthermore, B-cell lymphoma-2 (Bcl-2) expression was increased, while Bcl-2-associated X protein (Bax) and cleaved-caspase-3 was decreased in response to application of RIPostC. Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation. The significance of this study is to provide a theoretical basis for further exploring the protective mechanism of ischemic stroke by RIPostC. RESEARCH HIGHLIGHTS: Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation, thus achieving a neuroprotective effect.

Oral anticoagulants status after acute ischemic stroke and prognosis in patients with atrial fibrillation.

OBJECTIVES: To investigate the oral anticoagulants (OACs) use after acute ischemic stroke (AIS) and prognosis of patients with atrial fibrillation (AF). METHODS: This was a real-world follow-up research of AIS patients with AF admitted to 5 hospitals in northwestern China. We visited these individuals every 6 months to check the type, dosage of OACs, and to record IS recurrence, bleeding, and death events and modified Rankin Scale (mRS) scores until December 2022. When one of the following occurring first was endpoint: IS recurrence, death or study end. Patients were divided into continuous anticoagulation group and non-continuous anticoagulation group based on whether they continued to take OACs from the moment they were discharged until the endpoint. We further analyzed the association between anticoagulation persistence and outcomes. RESULTS: Among all 250 patients with OACs indication, 147 patients (58.8 %) received OACs at discharge. Only 37.9 % of patients (39/103) started OACs after discharge. Of the 147 patients treated with OACs, 21.8 % (32/147) discontinued anticoagulation after discharge. 239 of the 250 patients had completed the median 40-month follow-up with 91 patients in continuous anticoagulation group and 148 patients in non-continuous anticoagulation group. In the multivariate COX regression, non-continuous anticoagulation was an independent risk factor for poor prognosis (mRS>2) in AIS patients with AF (1.452[1.011, 2.086], p = 0.043). CONCLUSIONS: This study revealed an upward trend in the use rate of OACs, but low OACs rates that meet guideline-based criteria and low anticoagulation persistence in AF patients after AIS in the northwestern China. Discontinuous anticoagulation was associated with an increased risk of poor prognosis in these patients.

[Clinical observation of virtual reality technology combined with isokinetic strength training for patients after anterior cruciate ligament reconstruction].

OBJECTIVE: To explore application value and effectiveness of virtual reality technology combined with isokinetic muscle strength training in the rehabilitation of patients after anterior cruciate ligament (ACL) reconstruction surgery. METHODS: Forty patients who underwent ACL reconstruction surgery from December 2021 to January 2023 were selected and divided into control group and observation group according to treatment methods, 20 patients in each group. Control group was received routine rehabilitation training combined with isokinetic muscle strength training, including 15 males and 5 females, aged from 17 to 44 years old, with an average of (29.10±8.60) years old. Observation group was performed virtual reality technology combined with isokinetic muscle strength training, including 16 males and 4 females, aged from 17 to 45 years old with an average of (30.95±9.11) years old. Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups at 12 (before training) and 16 weeks (after training) after surgery were compared. RESULTS: All patients were followed up for 1 to 6 months with an average of (3.30±1.42) months. There were no statistically significant difference in Lysholm knee joint score, peak knee extension peak torque, and peak knee flexion peak torque between two groups (P>0.05) before training. After training, Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque of both groups were improved compared to before training (P<0.05);there were significant difference in Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups(P<0.05). CONCLUSION: The application of virtual reality technology combined with isokinetic muscle strength training could promote recovery of knee joint function and enhance muscle strength in patients after ACL reconstruction surgery in further.

Efficacy and safety of eptinezumab in patients with chronic migraine and medication-overuse headache: a randomized, double-blind, placebo-controlled study.

BACKGROUND: For some people with migraine, despite taking greater amounts of acute headache medication (AHM), they develop an increase in monthly headache days. This cycle of increasing headache days, and in turn AHM use, can lead to a secondary headache disorder called medication-overuse headache (MOH). Preventive medications can prevent migraine from occurring and reduce reliance on AHMs, thereby preventing the cycle of MOH. This study was performed to evaluate the efficacy and safety of eptinezumab to prevent migraine/headache in a mainly Asian patient population with a dual diagnosis of chronic migraine and MOH. METHODS: SUNLIGHT was a phase 3, multicenter, double-blind, parallel-group, placebo-controlled trial. Patients aged 18-75 years with ≥ 8 migraine days/month and a diagnosis of MOH were randomly allocated (1:1) to one of two treatment groups: eptinezumab 100 mg or placebo. Monthly migraine days (MMDs) were captured using a daily electronic diary; the change from baseline in the number of MMDs over Weeks 1-12 was the primary efficacy endpoint. RESULTS: Patients were randomized to eptinezumab 100 mg (n = 93) or placebo (n = 100). Over Weeks 1-12, eptinezumab reduced mean MMDs more than placebo (difference between treatments was -1.2; p = 0.1484). Differences between treatment groups with p-values below 0.05 favoring eptinezumab were observed in 3 out of the 6 key secondary endpoints. CONCLUSION: All endpoints numerically favored eptinezumab treatment when compared to placebo; however, this study did not meet its primary endpoint and is therefore negative. No new safety signals were identified in this study, like previous reports that confirmed the safety and tolerability of eptinezumab treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04772742 (26/02/2021).

Resting-state electroencephalography microstate dynamics altered in patients with migraine with and without aura-A pilot study.

OBJECTIVE: To evaluate electroencephalography (EEG) microstate differences between patients with migraine with aura (MWA), patients with migraine without aura (MWoA), and healthy controls (HC). BACKGROUND: Previous research employing microstate analysis found unique microstate alterations in patients with MWoA; however, it is uncertain how microstates appear in patients with MWA. METHODS: This study was conducted at the Headache Clinic of the First Affiliated Hospital of Xi'an Jiaotong University. In total, 30 patients with MWA, 30 with MWoA, and 30 HC were enrolled in this cross-sectional study. An EEG was recorded for all participants under resting state. The microstate parameters of four widely recognized microstate classes A-D were calculated and compared across the three groups. RESULTS: The occurrence of microstate B (MsB) in the MWoA group was significantly higher than in the HC (p = 0.006, Cohen's d = 0.72) and MWA (p = 0.016, Cohen's d = 0.57) groups, while the contribution of MsB was significantly increased in the MWoA group compared to the HC group (p = 0.016, Cohen's d = 0.64). Microstate A (MsA) displayed a longer duration in the MWA group compared to the MWoA group (p = 0.007, Cohen's d = 0.69). Furthermore, the transition probability between MsB and microstate D was significantly increased in the MWoA group compared to the HC group (p = 0.009, Cohen's d = 0.68 for B to D; p = 0.007, Cohen's d = 0.71 for D to B). Finally, the occurrence and contribution of MsB were positively related to headache characteristics in the MWoA group but negatively in the MWA group, whereas the duration of MsA was positively related to the visual analog scale in the MWA group (all p < 0.05). CONCLUSIONS: Patients with MWA and MWoA have altered microstate dynamics, indicating that resting-state brain network disorders may play a role in migraine pathogenesis. Microstate parameters may have the potential to aid clinical management, which needs to be investigated further.

Galcanezumab in patients with episodic migraine: results from the open-label period of the phase 3 PERSIST study.

BACKGROUND: The phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia. METHODS: Patients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE. Patients previously randomized to galcanezumab (GMB/GMB group) continued to receive galcanezumab 120 mg at all three visits during the OLE whereas patients randomized to placebo received a 240 mg loading dose of galcanezumab and then two 120 mg doses (PBO/GMB group). The primary outcome was the mean change (from double-blind baseline) in the number of monthly migraine headache days (MHDs) to month 6. Other endpoints included percent reduction in monthly MHDs from double-blind baseline to month 6, functional outcomes, safety and tolerability. RESULTS: Overall, 99% of patients completing the double-blind period entered the OLE, and 96% completed through month 6. Patients in the GMB/GMB group achieved continued improvements in efficacy, with the reduction from baseline in the mean number of monthly MHDs, and slightly increasing from 4.01 days at the end of the double-blind period to 4.62 at the end of the OLE. Of patients who were ≥ 50% responders to galcanezumab at month 3, 66% maintained this response through to month 6. Patients in the PBO/GMB group experienced a rapid reduction in the number of monthly MHDs after initiation of galcanezumab, with a mean reduction from baseline of 4.56 days by month 6. The long-term benefits of galcanezumab were also supported by improvements in other efficacy and functional endpoints. All safety findings were consistent with the known long-term safety profile of galcanezumab; no patients experienced a treatment-related serious adverse event. CONCLUSIONS: Galcanezumab was efficacious and well-tolerated in patients with episodic migraine from China, India and Russia, for up to 6 months. TRIAL REGISTRATION: ClinicalTrisABSTRACT_pals.gov NCT03963232, registered May 24, 2019.

Case report and literature review: fatal cerebral fat embolism following facial autologous fat graft.

Background: Severe cerebral artery embolism is a rare complication of facial autologous fat injection. However, its incidence has markedly increased with the recent rise in facial cosmetic procedures. Case presentation: We report a 31-year-old Chinese woman who presented with unconsciousness 6 h after having undergone a facial autologous fat injection. A neurological examination revealed stupor, bilaterally diminished pupillary light reflexes, right-sided central facial palsy, and no reaction to pain stimulation of right limbs. Diffusion-weighted imaging displayed patchy hyperintense lesions in the left frontal, parietal, and temporal lobes. Magnetic resonance angiography demonstrated fat embolism in the left internal carotid artery, anterior cerebral artery, and middle cerebral artery. We immediately performed mechanical thrombectomy under sufficient preoperative preparations but failed to achieve complete recanalization. Pathological examination of the embolus confirmed the presence of adipocytes. Although we actively administered symptomatic and supportive treatments, the patient eventually died due to the progression of cerebral herniation and systemic infection. Conclusion: Due to the ineffectiveness of current treatment and the inferior prognosis, fat embolism, a severe complication of autologous fat graft, should draw the attention of both plastic surgeons and neurologists so that actions may be taken for both its prevention and treatment.

Post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia: a case report.

BACKGROUND: Pneumocephalus is rare in vaginal deliveries. Pneumocephalus may be asymptomatic or present with signs of increased intracranial pressure. However, parturients who received epidural anesthesia with air in their brains may experience low intracranial pressure headaches after giving birth, causing the diagnosis of pneumocephalus to be delayed. We report a case of a parturient who developed post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia. CASE PRESENTATION: A 24-year-old G1P0 Chinese woman at 38 weeks gestation was in labor and received epidural anesthesia using the loss of resistance to air technique and had a negative prior medical history. She presented with postural headache, neck stiffness and auditory changes 2 h after vaginal delivery. The head non-contrast computed tomography revealed distributed gas density shadows in the brain, indicating pneumocephalus. Her headache was relieved by bed rest, rehydration, analgesia, and oxygen therapy and completely disappeared after 2 weeks of postpartum bed rest. CONCLUSIONS: This is the first report that positional headaches after epidural anesthesia may not indicate low intracranial pressure alone; it may combine with pneumocephalus, particularly when using the loss of resistance to air technique. At this moment, head computed tomography is essential to discover other conditions like pneumocephalus.

The patent foramen ovale may alter migraine brain activity: A pilot study of electroencephalography spectrum and functional connectivity analysis.

Background: A link has been shown between patent foramen ovale (PFO) and migraine, particularly migraine with aura. However, it is unknown if PFO might cause migraine by altering cortical excitability and neural network, which may lower the threshold of cortical spreading depression (CSD). This study aims to compare the spectrum power and functional connectivity of the alpha and beta bands of electroencephalography (EEG) across migraine patients with and without PFO. Methods: Thirty-five migraine patients with PFO (PFO +), 35 migraine patients without PFO (PFO -) and 20 PFO patients without migraine (control) were enrolled in this cross-sectional analysis. 19-channel EEG was recorded for all patients under resting state and intermittent photic stimulation. Power spectrum density (PSD) and phase lag index (PLI) of alpha and beta bands were then calculated and compared between the three groups. Results: During photic stimulation, the beta band PSD at the occipital area was substantially higher in PFO + migraine patients compared to PFO-migraine patients (p < 0.05, Bonferroni corrected). Subgroup analysis showed that both migraine with and without aura patients with PFO had increased PSD in the alpha and beta bands at the occipital region during photic stimulation (p < 0.05, Bonferroni corrected). Meanwhile, the beta band PLI during photic stimulation was significantly elevated (adjusted p = 0.008, utilizing the network-based statistic technique) in PFO + group compared to PFO-group. Furthermore, although failed to pass the correction, the beta band power in the occipital area during photic stimulation at 20 Hz on O1 (R = 0.392, p = 0.024) and O2 channel (R = 0.348, p = 0.047) was prone to positively correlated with MIDAS score, and during photic stimulation at 12 Hz on O2 channel (R = 0.396, p = 0.022) and 20 Hz (R = 0.365, p = 0.037) on O1 channel was prone to positively correlated to HIT-6 score in PFO+ migraineurs, whereas no similar correlation was found in the PFO-group patients. Conclusion: The outcomes of this investigation suggested that PFO may change the cortical excitability in the occipital lobe of both migraineurs with and without aura. Meanwhile, the beta band PSD on the occipital area during photic stimulation might be an objective measure of severity in migraineurs with PFO.

Electroencephalographic power spectrum changes in cerebral small vessel disease combined with cognitive dysfunction and its relationship with neutrophil/lymphocyte ratio and its clinical value - a pilot study.

Objective: The study aimed to explore the changes in the electrical power spectrum of the brain and its correlation with neutrophil/lymphocyte ratio (NLR) in patients with cognitively impaired cerebral small vessel disease (CSVD) and to explore its clinical application. Methods: A total of 61 patients with CSVD who attended the People's Hospital of Shaanxi Province from September 2021 to September 2022 were divided into the group with cognitive impairment (cerebral small vascular with cognitive impairment, CSVCI group, n = 29) and the group without cognitive impairment (CSVD group, n = 32) based on the Montreal Cognitive Assessment Scale (MoCA) score, while 20 healthy subjects were recruited as the control group (healthy control, HC group). EEG was performed in the three groups, and the difference in whole brain quantitative EEG power spectral density (PSD) was calculated and compared between the three groups. Results: The PSD values in the δ and θ bands of the CSVCI group were higher than those of the CSVD group, while the PSD values in the α band were lower than those of the CSVD and HC groups. In addition, PSD values in the δ-band in the CSVD group were lower than those in the HC group (all p < 0.05). Multifactorial logistic regression showed that reduced α-band global average PSD and low years of education were independent risk factors for cognitive impairment in patients with CSVD (p < 0.05). In patients with cerebral small-vessel disease, α-band PSD was positively and δ-band PSD negatively correlated with MoCA score, and paraventricular, deep white matter, and total Fazekas scores were negatively correlated with MoCA score. Furthermore, θ-band PSD is positively correlated with NLR (all p < 0.05). Conclusion: EEG activity was slowed down in patients with CSVD with cognitive impairment. The α-band global mean PSD values independently affected the occurrence of cognitive impairment in CSVD patients beyond the Fazekas score. NLR may be one of the mechanisms leading to the slowing down of the EEG, which can be used as an objective indicator for the early prediction of cognitive impairment but still needs to be clarified by further studies.

Cerebral Small Vessel Diseases and Outcomes for Acute Ischemic Stroke Patients after Endovascular Therapy.

The correlation between cerebral small vessel disease (CSVD) and the outcomes of acute ischemic stroke (AIS) patients after endovascular therapy (EVT) remains elusive. We aimed to investigate the effect of combined white matter hyperintensities (WMH) and enlarged perivascular spaces (EPVS) as detected in magnetic resonance imaging (MRI) at baseline on clinical outcomes in patients with AIS who underwent EVT. AIS patients that experienced EVT were retrospectively analyzed in this single-center study. Using MRIs taken prior to EVT, we rated WMH and EPVS as the burden of CSVD and dichotomized the population into two groups: absent-to-moderate and severe. Neurological outcome was assessed at day 90 with a modified Rankin Scale (mRS). Symptomatic intracerebral hemorrhage (sICH), early neurological deterioration (END), malignant cerebral edema (MCE), and hospital death were secondary outcomes. Of the 100 patients (64.0% male; mean age 63.71 ± 11.79 years), periventricular WMHs (28%), deep WMHs (41%), EPVS in basal ganglia (53%), and EPVS in centrum semiovale (73%) were observed. In addition, 69% had an absent-to-moderate total CSVD burden and 31.0% had a severe burden. The severe CSVD was not substantially linked to either the primary or secondary outcomes. Patients with AIS who underwent EVT had an elevated risk (OR: 7.89, 95% CI: 1.0, 62.53) of END if they also had EPVS. When considering WMH and EPVS together as a CSVD burden, there seemed to be no correlation between severe CSVD burden and sICH, END, or MCE following EVT for AIS patients. Further studies are warranted to clarify the relationship between CSVD burden and the occurrence, progression, and prognosis of AIS.

Safety Findings in Lasmiditan as a Novel Acute Treatment of Migraine in Chinese Patients: A Post Hoc Analysis of the Randomized Controlled Phase 3 CENTURION Trial.

INTRODUCTION: Lasmiditan is the first 5-HT1F receptor agonist with potential to address the huge unmet medical needs for the treatment of migraine in China. The CENTURION study was the first phase 3 study of lasmiditan in Caucasian and Chinese patients with migraine. This post hoc analysis further demonstrates the safety profile of lasmiditan in the Chinese population and was urgently needed. METHODS: Patients were randomized 1:1:1 to lasmiditan 200 mg lasmiditan 100 mg, or a control group. The incidence of treatment-emergent adverse events (TEAEs), their severity, and incidence by treated attacks for frequently reported TEAEs (≥ 5%) were evaluated. The duration, onset, and relationship of efficacy with very common TEAEs (≥ 10%) was analyzed. RESULTS: A total of 281 Chinese patients were included in this post hoc analysis. No deaths and no study drug-related treatment emergent serious adverse events (TESAEs) were reported. The incidence of at least one TEAE was higher in patients receiving lasmiditan 200 mg (73.9%) and 100 mg (66.3%) versus placebo (26.6%). TEAEs were generally mild or moderate in severity, and the incidence of frequently reported TEAEs was generally highest during the first attack. Very common TEAEs with lasmiditan included dizziness, asthenia, somnolence, muscular weakness, fatigue, and nausea. The duration of dizziness was longest during the first attack. There were no cardio-cerebrovascular ischemic events and serotonin syndrome. The presence of very common TEAEs (except nausea), and severe dizziness, did not appear to have a negative influence on the efficacy. CONCLUSION: In the Chinese population of the CENTURION study, most of the TEAEs were neurologic, of mild or moderate severity, and self-limiting. The distribution of frequently reported TEAEs at the first attack differed from the primary cohort, while the overall safety profile of lasmiditan in the Chinese population was generally consistent with the CENTURION primary cohort. No new safety concerns were observed in the Chinese population. TRIAL REGISTRATION: NCT03670810.

Although there is significant unmet medical need among patients with migraine, there has been no novel compound for treatment of migraine over past two decades in China. These unmet medical needs persist because the current available medications for the acute treatment of migraine are reported to have safety and tolerability issues. Lasmiditan is a new class of acute migraine medication (5-HT receptor agonist with high selectivity for the 5-HT_1F receptor) with a proven efficacy and safety in phase 2 and 3 studies. Owing to some differences in clinical practice between China and western countries, there is need to get additional evidence on safety of lasmiditan in the Chinese population to support its usage in clinical practice.This post hoc analysis was conducted to present the detailed safety profile of lasmiditan in the Chinese population using data from the CENTURION study. Approximately half of the analyzed population was not covered in the published primary cohort.The results show that in the Chinese population of the study, most of the treatment-emergent adverse events (TEAEs) were neurologic, of mild or moderate severity, and self-limiting. The distribution of frequently reported TEAEs at the first attack differed from the primary cohort with no new safety concerns observed in the Chinese population. The overall safety profile of lasmiditan in the Chinese population was generally consistent with the primary cohort. The results provide additional evidence and emphasize that lasmiditan may be considered as a useful acute treatment option with acceptable safety profile for patients with migraine in China.