Headache is the symptom of pain in the face, head or neck that causes disability in most people with medical and neurological disorders. It frequently co-occurs with most chronic diseases such as epilepsy and significantly impacts the quality of life. However, epidemiologic data from different studies showed different rates of prevalence. Therefore, we conducted this review to summarize the available epidemiologic evidence on the topic and formulate recommendations for future research and clinical practice. We followed the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. We systematically searched the literature using popular databases such as PubMed, EMBASE, Psych-INFO, and SCOPUS. We further scanned the reference lists of the eligible studies to supplement our electronic search. The Comprehensive Meta-Analysis software version 3.0 (CMA 3.0) was used to conduct a meta-analysis. Subgroup and sensitivity analysis were performed and Cochran’s Q- and the I2- test were used to assess the source of heterogeneity. The funnel plot and Egger’s regression tests were used to assess potential publication bias. A total of 17 studies conducted both in developed and developing countries including 5564 study participants were combined in this meta-analysis. The pooled estimated prevalence of headache among patients with epilepsy was 48.4%. The pooled estimated prevalence of Inter-Ictal headache (IIH) (42.2%) and Postictal headache (PIH) (43.1%) were higher when compared to tension-type headache (TTH) (26.2%), migraine with aura (26.0%) and migraine without aura (10.4%). The pooled prevalence of headache was 50.6% and 49.5% for developed and developing countries respectively. The pooled prevalence of headache among patients with epilepsy was considerably higher among females (63.0%) when compared to males (33.3%). Moreover, the pooled estimated prevalence of headache among patients with epilepsy was ranging from 46.0% to 52.2% in a leave-one-out sensitivity analysis. The pooled estimated prevalence of headache among patients with epilepsy was considerably high (48.4%). Screening and appropriate management of headaches among patients with epilepsy are warranted.

/pdf/the-epidemiology-of-headaches-among-patients-with-epilepsy-a-54hqapow9w.pdf

The epidemiology of headaches among patients with epilepsy: a systematic review and meta-analysis

Patent foramen ovale (FOP) is the most prevalent cause of cryptogenic strokes in people under 60 years old. Although it is usually asymptomatic, it has a high risk of producing paradoxical embolism and, therefore, stroke with indeterminate outcomes. The study should be started based on clinical suspicion, and includes a multidisciplinary assessment and a determination of the type of treatment to be performed. The therapeutic possibilities range from conservative treatment (indefinite antithrombotic treatment), to its percutaneous closure (currently the most widely used). The first objective is to decrease the number of stroke recurrences. Conservative treatment should be reserved for those cases of low embolic risk. The risk assessment must be individualised, fundamentally based on the anatomical characteristics of the FOP and the patient clinic picture. The use of the RoPE risk scale (The Risk of Paradoxical Embolism) should be a tool to consider.

Foramen oval permeable. Una actualización para atención primaria

Epilepsy and migraine are among the most prevalent neurological disorders. By being comorbid, the presence of one disorder increases the likelihood of the other. Although several similar clinical features of epilepsy and migraine have been observed as early as the 19th century, only in recent years have researchers engaged in finding a common pathogenic mechanism between them. In this study, the epilepsy–migraine comorbidity rat model was generated, and the pathophysiological basis of epilepsy–migraine comorbidity was examined. Male rats were divided into four groups: control, migraine, epilepsy, epilepsy–migraine comorbidity. After establishing the models, the amount of scratching and the pain threshold of the rats were observed. Western blot and immunofluorescence staining were used to detect the protein expression levels of TLR4 and GABAARα1 in the temporal cortex, hippocampus, trigeminal ganglion, and medullary dorsal horn. Subsequently, co-immunoprecipitation of GABAARα1 and TLR4 was performed. Then, the rats were divided into three groups: comorbidity, comorbidity + TAK-242, and comorbidity + muscimol. After drug intervention, the seizure latency, seizure level, amount of scratching, and pain threshold were observed. Western blot was used to detect the protein expression levels of TLR4 and GABAARα1 in the temporal cortex, hippocampus, trigeminal ganglion, and medullary dorsal horn. Our results demonstrate that the seizure attacks in comorbidity and epilepsy groups performed severely, and the comorbidity and migraine groups displayed a remarkable increase in the amount of head-scratching and a noticeable decrease in the facial mechanical withdrawal threshold. Further analysis revealed considerably increased Toll-like receptor 4 (TLR4), associated with reduced γ-aminobutyric acid type A receptor α1 (GABAARα1) and microglia enhanced in the epilepsy–migraine comorbidity rat. Additionally, co-immunoprecipitation proved GABAARα1 binding TLR4. Following muscimol to activate GABAARα1, seizure attacks and migraine-like behavior were rescued. GABAARα1 level increment was accompanied by the decline of TLR4, while TAK-242, the inhibitor of TLR4, only decreased TLR4 without affecting GABAARα1 expression. It also ameliorated the migraine-like behavior with no impact on seizure activity. We propose that GABAARα1 binding and negatively regulating TLR4 contribute to epilepsy–migraine comorbidity; TLR4 is a critical intermediate link in epilepsy–migraine comorbidity; immune-induced neuroinflammation in microglia may be involved in migraine and epilepsy–migraine comorbidity.

/pdf/downregulation-of-gabaara1-aggravates-comorbidity-of-2nbsd1ar.pdf

Downregulation of GABAARα1 Aggravates Comorbidity of Epilepsy and Migraine via the TLR4 Signaling Pathway

Abstract Objectives Epilepsy and migraine are common chronic neurological disease. Epidemiologic studies and shared pathophysiology and treatment suggest that these two diseases overlap. However, migraine is often underestimated among patients with epilepsy. This study aimed to evaluate the prevalence of migraine and identify the related influencing factors among adult patients with epilepsy. Methods Adult patients with epilepsy were recruited at the outpatient epilepsy clinic of 13 tertiary hospitals in China from February to September 2022. ID Migraine questionnaire was applied to evaluate for migraine. Both univariable and multivariable logistic regression models were used to explore the influencing factors of migraine. Results A total of 1326 patients with epilepsy were enrolled in this study. The prevalence of migraine among patients with epilepsy was 19.2% (254/1326). In the multivariable analysis, being female (OR = 1.451, 95% CI: 1.068–1.975; p = 0.018), focal and focal to bilateral tonic–clonic seizures (OR = 1.583, 95% CI: 1.090–2.281; p = 0.015), and current seizure attack in the last 3 months (OR = 1.967, 95% CI: 1.282–3.063; p = 0.002) were the influencing factors for migraine. However, &lt;10% of patients with epilepsy received analgesics for migraine. Significance Approximately 20% of patients with epilepsy screened positive for migraine. Being female, focal and focal to bilateral tonic–clonic seizures, and current seizure attack in the last 3 months were the influencing factors for migraine. Neurologists should pay more attention to the screening and management of the migraine among patients with epilepsy in China. Plain Language Summary Epilepsy and migraine are common chronic neurological disease with shared pathophysiological mechanisms and therapeutic options. However, migraine is often underestimated among patients with epilepsy. This multicenter study aimed to evaluate the prevalence of migraine and current status of treatment. In this study, approximately 20% of patients with epilepsy screened positive for migraine. Female, focal and focal to bilateral tonic–clonic seizures, and current seizure attack in the last 3 months were identified as independent influencing factors for migraine. Despite the high prevalence, the treatment for migraine was not optimistic, neurologists should pay more attention to the screening and management of migraine. 

A cross‐sectional, multicenter survey of the prevalence and influencing factors for migraine in epilepsy

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.

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

Objectives To investigate the relationship between right-to-left shunt and migraine to account for the unexplained high prevalence of migraine in patients with epilepsy. Design This is a cross-sectional study. The diagnosis and interview process of patients with migraine was based on the International Classification of Headache Disorders-3 beta in patients with epilepsy. Participants underwent transthoracic echocardiography (TTE) with contrast medium to identify right-to-left shunt. The highest number of microbubbles were recorded in the left atrium before the complete microbubble outflow of the right atrium. A moderate-to-large shunt was defined as the presence of 10 or more microbubbles. Setting A single-centre, cross-sectional study in China, 2015–2017. Participants Patients with epilepsy. Primary and secondary outcome measures The primary outcome measures were the prevalence of migraine, the prevalence of right-to-left shunt in patients with migraine and those without migraine, and the prevalence of migraine in different degrees of shunting. Results Three hundred thirty-nine participants with epilepsy who completed TTE were included in the analysis. The overall prevalence of migraine was 23.0%. One-third of the migraineurs had mild right-to-left shunt and one-fifth of the migraineurs had moderate-to-large right-to-left shunt. Patients with mild shunt did not have a higher prevalence of migraine than those without shunt (26.3% vs 18.1%, p=0.102); however, a higher prevalence of migraine was found in patients with moderate-to-large shunt (39.0% vs 18.1%, OR=2.90, 95% CI=1.41 to 5.98, p=0.003). Patients with migraine and patients without migraine had similar prevalence of mild shunt; however, patients with migraine had more moderate-to-large shunt (20.5% vs 9.6%, p=0.002). Right-to-left shunt and female were factors predicting migraine prevalence. Conclusions One-fifth of migraineurs were correlated with moderate-to-large right-to-left shunt which could be an underlying cause of migraine in epilepsy.

https://bmjopen.bmj.com/content/bmjopen/8/10/e024144.full.pdf

Relationship between right-to-left shunt and migraine in patients with epilepsy: a single-centre, cross-sectional study in China.

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Relationship between right-to-left shunt and migraine in patients with epilepsy: a single-centre, cross-sectional study in China.