Therapeutic value of patent foramen ovale closure for drug-resistant epilepsy: A case series report.

OBJECTIVE: Closure surgery of patent foramen ovale (PFO) has been found to effectively control cryptogenic stroke and migraine, but it is uncertain whether PFO closure could also alleviate epileptic seizures. This study aims to observe the therapeutic effect of PFO closure on epileptic seizures. METHODS: Since July 11th, 2017, in the neurology department of West China Hospital, Sichuan University, Chengdu, we have been regularly monitoring patients with epilepsy who have undergone PFO closure. The patient's clinical information, such as frequency, duration, and severity of seizures, before and after surgery was recorded in detail as well as postoperative safety events. RESULTS: Of the 31 epilepsy patients who confirmed PFO observed (27 cases were drug-resistant epilepsy, 87.10%), average age of surgery was 23.74 years, and 12 cases were female (38.71%). After one-year follow-up, 26 patients (83.87%) achieved remission of seizure frequency, and 22 of whom (70.97%) experienced a remission of more than 50%. Additionally, compared to before surgery, 22 cases (70.97%) reported a decrease in the average seizure duration, and 20 cases (64.52%) reported a reduction in seizure severity. In the seizure indicators of frequency, average duration and severity, significant differences were identified between preoperative and postoperative comparisons with all test p values were <0.05. Furthermore, no serious safety events were reported except for one patient who briefly reported chest pain, and all patients expressed effective PFO closure. SIGNIFICANCE: The PFO closure has been shown for the first time to result in a significant reduction in the frequency, duration, and severity of seizures. Patients with drug-resistant epilepsy and PFO with a large shunt are ideal candidates for undergoing PFO closure. PLAIN LANGUAGE SUMMARY: Since PFO closure was found to have a good therapeutic effect on cryptogenic stroke and migraine, it has become a credible complementary therapy for the treatment of neurological diseases, and drug-resistant epilepsy with PFO is expected to become the next target disease that PFO closure could significantly improve.

Association between patent foramen ovale and migraine: evidence from a resting-state fMRI study.

A relationship between migraine without aura (MO) and patent foramen ovale (PFO) has been observed, but the neural basis underlying this relationship remains elusive. Utilizing independent component analysis via functional magnetic resonance imaging, we examined functional connectivity (FC) within and across networks in 146 patients with MO (75 patients with and 71 patients without PFO) and 70 healthy controls (35 patients each with and without PFO) to elucidate the individual effects of MO and PFO, as well as their interaction, on brain functional networks. The main effect of PFO manifested exclusively in the FC among the visual, auditory, default mode, dorsal attention and salience networks. Furthermore, the interaction effect between MO and PFO was discerned in brain clusters of the left frontoparietal network and lingual gyrus network, as well as the internetwork FC between the left frontoparietal network and the default mode network (DMN), the occipital pole and medial visual networks, and the dorsal attention and salience networks. Our findings suggest that the presence of a PFO shunt in patients with MO is accompanied by various FC changes within and across networks. These changes elucidate the intricate mechanisms linked to PFO-associated migraines and provide a basis for identifying novel noninvasive biomarkers.

Risk assessment model for sleep disturbance based on gastrointestinal myoelectrical activity in middle-aged and elderly people.

Background: Sleep disturbance has become a considerable factor affecting the quality of life for middle-aged and elderly people; however, there are still many obstacles to screening sleep disturbance for those people. Given the growing awareness of the association between gastrointestinal function and sleep disturbance, our study aims to predict the risk of sleep disturbance using gastrointestinal electrophysiological signals. Methods: The Pittsburgh Sleep Quality Index and gastrointestinal electrophysiological signals of 914 participants in western China were used to establish the model. Demographic characteristics and routine blood test were collected as covariates. Participants were randomly assigned into two sets with a 7:3 ratio for training and validation. In the training set, the least absolute shrinkage and selection operator (LASSO) regression and stepwise logistic regression were used, respectively for variables selection and optimization. To assess the model performance, receiver operator characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were utilized. Then, validation was performed. Results: Thirteen predictors were chosen from 46 variables by LASSO regression. Then, age, gender, percentage of normal slow wave and electrical spreading rate on the pre-meal gastric channel, dominant power ratio on the post-meal gastric channel, coupling percent and dominant frequency on the post-meal intestinal channel were the seven predictors reserved by logistic regression. The area under ROC curve was 0.65 in the training set and 0.63 in the validation set, both exhibited moderate predictive ability. Furthermore, by overlapping the DCA results of two data-sets, there might be clinical net benefit if 0.35 was used as reference threshold for high risk of sleep disturbance. Conclusion: The model performs a worthy predictive potency for sleep disturbance, which not only provides clinical evidence for the association of gastrointestinal function with sleep disturbance, but also can be considered as an auxiliary assessment for screening sleep disturbance.

Association of patent foramen ovale with epilepsy: A hospital-based case-control study.

OBJECTIVE: This study aimed to investigate the proportion of patent foramen ovale (PFO) in people with epilepsy (PWE) compared to controls without epilepsy and to assess whether PWEs with and without PFO exhibit distinctive clinical features. METHODS: This is a case-control study conducted in a hospital. Contrast transthoracic echocardiography with a venous microbubble bolus and provocative maneuvers (Valsalva and coughing) were used to identify PFO and its right-to-left shunt (RLS) among 741 PWEs and 800 controls without epilepsy. The risk of having PFO in PWEs was explored using multiple matching methods and logistic regression with adjusted congenital factors that may affect the occurrence of PFO. RESULTS: The proportion of PFO in PWEs and controls was 39.00% and 24.25%, respectively. After 1:1 propensity score matching, the risk of suffering PFO in PWEs was 1.71 times (OR, 1.71; 95% CI, 1.24-2.36) higher than that in controls. PWEs also had a higher risk of having a high RLS grade (ßepilepsy = 0.390, P < 0.001). Among clinical characteristics of PWEs, migraine, and drug-resistant epilepsy showed significantly different distributions between those without RLS and those with RLS grade I to III. PWEs with PFO had higher risk of suffering from migraine and drug-resistant epilepsy (OR in migraine, 2.54, 95% CI, 1.65-3.95; OR in drug-resistant epilepsy, 1.47, 95% CI, 1.06-2.03). SIGNIFICANCE: The proportion of PFO was found to be higher in PWE than in controls without epilepsy, especially in patients with drug-resistant epilepsy, suggesting potential relationship between the two disorders. Large multicentric study will be needed to confirm this finding.

Connection between right-to-left shunt and photosensitivity: a community-based cross-sectional study.

Background: Hypersensitivity to light is a common symptom associated with dysfunction of the occipital region. Earlier studies also suggested that clinically significant right-to-left shunt (RLS) could increase occipital cortical excitability associated with the occurrence of migraine. The aim of this study was to investigate the relationship between RLS and photosensitivity. Methods: This cross-sectional observational study included the residents aged 18-55 years living in the Mianzhu community between November 2021 and October 2022. Photosensitivity was evaluated using the Photosensitivity Assessment Questionnaire along with baseline clinical data through face-to-face interviews. After the interviews, contrast-transthoracic echocardiography (cTTE) was performed to detect RLS. Inverse probability weighting (IPW) was used to reduce selection bias. Photosensitivity score was compared between individuals with and without significant RLS using multivariable linear regression based on IPW. Results: A total of 829 participants containing 759 healthy controls and 70 migraineurs were finally included in the analysis. Multivariable linear regression analysis showed that migraine (ß = 0.422; 95% CI: 0.086-0.759; p = 0.014) and clinically significant RLS (ß = 1.115; 95% CI: 0.760-1.470; p < 0.001) were related to higher photosensitivity score. Subgroup analysis revealed that clinically significant RLS had a positive effect on hypersensitivity to light in the healthy population (ß = 0.763; 95% CI: 0.332-1.195; p < 0.001) or migraineurs (ß = 1.459; 95% CI: 0.271-2.647; p = 0.010). There was also a significant interaction between RLS and migraine for the association with photophobia (pinteraction = 0.009). Conclusion: RLS is associated with photosensitivity independently and might exacerbate photophobia in migraineurs. Future studies with RLS closure are needed to validate the findings. Trial registration: This study was registered at the Chinese Clinical Trial Register, Natural Population Cohort Study of West China Hospital of Sichuan University, ID: ChiCTR1900024623, URL: https://www.chictr.org.cn/showproj.html?proj=40590.

Heart-brain axis: Association of congenital heart abnormality and brain diseases.

Brain diseases are a major burden on human health worldwide, and little is known about how most brain diseases develop. It is believed that cardiovascular diseases can affect the function of the brain, and many brain diseases are associated with heart dysfunction, which is called the heart-brain axis. Congenital heart abnormalities with anomalous hemodynamics are common treatable cardiovascular diseases. With the development of cardiovascular surgeries and interventions, the long-term survival of patients with congenital heart abnormalities continues to improve. However, physicians have reported that patients with congenital heart abnormalities have an increased risk of brain diseases in adulthood. To understand the complex association between congenital heart abnormalities and brain diseases, the paper reviews relevant clinical literature. Studies have shown that congenital heart abnormalities are associated with most brain diseases, including stroke, migraine, dementia, infection of the central nervous system, epilepsy, white matter lesions, and affective disorders. However, whether surgeries or other interventions could benefit patients with congenital heart abnormalities and brain diseases remains unclear because of limited evidence.

Recent progress in patent foramen ovale and related neurological diseases: A narrative review.

Patent foramen ovale (PFO) is a common congenital cardiac abnormality when the opening of the interatrial septum is not closed in adulthood. This abnormality affects 25% of the general population. With the development of precision medicine, an increasing number of clinical studies have reported that PFO is closely related to various neurological diseases such as stroke, migraine, obstructive sleep apnea, and decompression syndrome. It has also been suggested that PFO closure could be effective for preventing and treating these neurological diseases. Therefore, increasing attention has been given to the prevention, diagnosis, and treatment of PFO-related neurological diseases. By reviewing existing literature, this article focuses on the pathogenesis, epidemiology, and clinical characteristics of PFO-related neurological diseases, as well as the prevention and treatment of different neurological diseases to discuss, and aims to provide current progress for this field and decision-making evidence for clinical practice.

Relationship between right-to-left shunt, hypoxia, and epilepsy.

OBJECTIVE: A right-to-left shunt (RLS) can mediate the hypoxic state, and hypoxemia is relevant for the development of drug-resistant epilepsy (DRE). The objective of this study was to identify the relationship between RLS and DRE and further investigate the contribution of RLS to the oxygenation state in patients with epilepsy (PWEs). METHODS: We performed a prospective observational clinical study of PWEs who underwent contrast medium transthoracic echocardiography (cTTE) between January 2018 and December 2021 at West China Hospital. The collected data included demographics, clinical features of epilepsy, antiseizure medications (ASMs), RLS identified by cTTE, electroencephalography (EEG), and magnetic resonance imaging (MRI). Arterial blood gas was also assessed in PWEs with or without RLS. The association between DRE and RLS was quantified using multiple logistic regression, and the parameters of oxygen levels were furtherly analyzed in PWEs with or without RLS. RESULTS: A total of 604 PWEs who completed cTTE were included in the analysis, of which 265 were diagnosed with RLS. The proportion of RLS was 47.2% in the group of DRE, and the proportion of RLS was 40.3% in the group of non-DRE. Having RLS was associated with DRE in multivariate logistic regression analysis (adjusted OR = 1.53, P = 0.045). In the analysis of blood gas, the partial oxygen pressure in PWEs with RLS was lower than those without RLS (88.74 mmHg versus 91.84 mmHg, P = 0.044). SIGNIFICANCE: Right-to-left shunt could be an independent risk factor of DRE, and low oxygenation might be a possible reason.

Association between patent foramen ovale and migraine without aura: a community-based cross-sectional study in China.

OBJECTIVES: To assess the influence of patent foramen ovale (PFO) on the prevalence of migraine without aura based on propensity score-matched samples in Southwest China. DESIGN: Propensity-matched cross-sectional study. PARTICIPANTS: Residents over 20 years of age were recruited from 15 communities of Western China from July 2020 to October 2020. A total of 3741 residents having accepted to undergo contrast-transthoracic echocardiography and a standard structured questionnaire was assessed for the relationship between PFO and migraine without aura. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were the prevalence of migraine without aura across different degrees of right-left shunts. RESULTS: A total of 3741 participants were included. Among them, 881 participants were diagnosed with PFO. The prevalence of migraine without aura in the PFO group was 12.83%, significantly higher than the other group (7.83%, p<0.0001). Analyses of the matched samples showed that the presence of a PFO increased the morbidity risk of migraine without aura (p < 0.001; OR=1.71, 95% CI 1.19 to 2.47). CONCLUSION: This community-based cross-sectional study pointed to a strong association between PFO and migraine without aura, especially when the shunt is large. TRIAL REGISTRATION NUMBER: ChiCTR1900024623.

Behavioral and Brain Structural Changes in Kindled Rats Induced by Coriaria Lactone/Pentylenetetrazol.

Epilepsy is a common chronic neurological disease that is characterized by spontaneous seizures. It is commonly comorbid with behavioral and mood disorders. No studies have yet examined the behavioral or structural brain changes associated with coriaria lactone (CL)-induced and pentylenetetrazol (PTZ)-induced kindlings. This study examined whether the increased seizure susceptibility induced by CL/PTZ is accompanied by behavioral impairments and aimed to identify associated structural brain changes. Kindling models were induced using CL and PTZ, with 10 rats in each group. After successful kindling, rats were subjected to brain structural imaging using T2-weighted imaging and underwent behavioral tests, namely, the open field test, water maze tasks, and contextual fear conditioning. Voxel-based morphometry was then used to identify possible brain structural changes associated with kindling and/or behaviors. Support-vector machine learning was also applied for the integrative analysis of behavioral changes and structural brain imaging. In the open field test, both the CL (P = 0.04) and PTZ groups (P = 0.002) spent more time in the central area than the control group. Only the PTZ group (50.29 ± 29.56 s) showed a freezing time that was significantly less than that of the control group (94.8 ± 41.04 s; P = 0.024, Tukey's HSD-corrected) in contextual fear conditioning, which is suggestive of impaired fear-associated learning ability. Furthermore, brain imaging analysis revealed that the gray matter volume (GMV) of the hippocampus changed in both the CL and PTZ groups when compared to control. The support-vector machine learning model indicated that the retrosplenial dysgranular and primary somatosensory cortices were associated with both of the mentioned kindling models. Furthermore, the support-vector regression model results indicated that kindling-associated GMV changes can be used to predict general exploratory activity in the open field test. In conclusion, this is the first study to report greater general exploratory activity in a CL-induced kindling model. Moreover, the general exploratory activity in the open field test can be predicted by the GMV of brain regions associated with kindling.

Association between loneliness, sleep behavior and quality: a propensity-score-matched case-control study.

OBJECTIVE: To explore the influence of loneliness on sleep behavior and sleep quality based on propensity score-matched samples in Southwest China. METHODS: Individual-level data were obtained from a Southwest China cohort study. Participants who felt lonely were matched with those who did not with propensity scores on the basis of age, gender, socioeconomic factors, physical exercise and social connection level. Sleep behavior (onset and offset timing), sleep quality (sleep latency, nocturnal awakenings and subjective sleep quality), and daytime function (daytime sleepiness and fatigue) were assessed with the Pittsburgh Sleep Index Scale (PSQI) and compared between the two groups. The data were collected between May 2019 and December 2019, and data analyses were completed in April 2021. RESULTS: A total of 11,696 participants were included, and 824 out of 839 participants who felt loneliness were statistically matched with 824 participants who did not. Analyses of the matched samples showed that sleep onset and offset timing were similar between those who felt lonely and those who did not (p = 0.110 and p = 0.751, respectively). Sleep latency was longer in those who felt lonely (26.84 [0.9] vs. 35.52 [1.2] min, p < 0.001) than in those who did not. Furthermore, participants who felt lonely tended to have poor subjective sleep, a higher frequency of nocturnal awakenings, daytime sleepiness and fatigue (all p < 0.001). CONCLUSIONS: Loneliness was associated with extended sleep latency, increased nocturnal awakenings, and reduced subjective sleep quality and daytime function but was not associated with sleep behavior, including sleep onset and offset timings.