Background: Previous studies have suggested that antidiabetic drug use may be associated with amyotrophic lateral sclerosis. However, these studies are limited by many confounding and reverse causality biases. We aimed to determine whether antidiabetic drug use has causal effects on ALS. Methods: Drug-target Mendelian randomization analysis was conducted to evaluate the association between genetic variation in the targets of antidiabetic drugs and ALS risk. The antidiabetic drugs included sulfonylureas, GLP-1 analogues, thiazolidinediones, insulin/insulin analogues, metformin, and SGLT2 inhibitors. Summary statistics for ALS were retrieved from previous genome-wide association studies comprising 27,205 ALS patients and 55,058 controls. The instrumental variables for these drugs are from previous published articles. Results: Genetic variation in SGLT2 inhibition targets was associated with lower risk of ALS (odds ratio [OR] = 0.32, 95% CI = 0.14-0.74; p = 0.008). We did not find that genetic variation in metformin targets was associated with ALS (OR = 1.61, 95% CI = 0.94-2.73; p = 0.081). Nevertheless, mitochondrial complex I, a target of metformin, was associated with a higher risk of ALS (OR = 1.83, 95% CI = 1.01-3.32; p = 0.047). The analysis showed that genetic variation in sulfonylureas, GLP-1 analogues, thiazolidinediones, insulin or insulin analogues targets was not associated with ALS (all p > 0.05). Conclusions: The complex interaction between hypoglycemic, antioxidation, and anti-inflammatory effects may account for the different results across antidiabetic drug types. These findings provide key evidence to guide the use of antidiabetic drugs and will help to identify novel therapeutic targets in ALS.

GGC repeat expansions in the 5’ untranslated region (5’UTR) of the Notch Homolog 2 N-terminal-like C gene (NOTCH2NLC) have been reported to be the genetic cause of neuronal intranuclear inclusion disease (NIID). However, whether they exist in other neurodegenerative disorders remains unclear. To determine whether there is a medium-length amplification of NOTCH2NLC in patients with amyotrophic lateral sclerosis (ALS), we screened 476 ALS patients and 210 healthy controls for the presence of a GGC repeat expansion in NOTCH2NLC by using repeat-primed polymerase chain reaction (RP-PCR) and fragment analysis. The repeat number in ALS patients was 16.11 ± 5.7 (range 7–46), whereas the repeat number in control subjects was 16.19 ± 3.79 (range 10–29). An intermediate-length GGC repeat expansion was observed in two ALS patients (numbers of repeats: 45, 46; normal repeat number ≤ 40) but not in the control group. The results suggested that the intermediate NOTCH2NLC GGC repeat expansion was associated with Chinese ALS patients, and further functional studies for intermediate-length variation are required to identify the mechanism.

Previous studies have found that migraine patients are associated with white matter lesions (WMLs), but the causal relationship between the two remains unclear. We intend to explore the bidirectional causal relationship between migraine and WMLs using a two-sample mendelian randomization (MR) method. We employed summary-level data from a recent large-scale genome-wide association study (GWAS) that characterized three white matter (WM) phenotypes: white matter hyperintensities (WMH, N = 18,381), fractional anisotropy (FA, N = 17,673), and mean diffusivity (MD, N = 17,467), as well as migraine (N = 589,356). The inverse variance-weighted (IVW) method was used as the main approach for analyzing causality. Weighted median analysis, simple median analysis, and MR-Egger regression served as complementary methods. The bidirectional MR study affords no support for causality between WMLs and migraine. In all MR methods, there was no obvious causal evidence between them. In our bidirectional MR study, we didn't reach this conclusion that WMLs can cause migraine, migraine wouldn’t increase the risk of WMLs, either.

Migraine is a common clinical primary headache with unclear aetiology. In recent years, studies have shown that migraine is related to right-to-left shunts (RLS), and some patients with migraine have white matter lesions. However, the relationship among the three is unclear. To explore the characteristics of white matter lesions (WMLs) in migraine patients with right-to-left shunts and to predict the presence of right-to-left shunts through magnetic resonance imaging (MRI) characteristics in patients with migraine, we conducted a retrospective study. We enrolled 214 patients who were diagnosed with migraines in an outpatient clinic from January 2019 to December 2021. All of them had completed contrast transcranial Doppler ultrasound (cTCD) and magnetic resonance imaging (MRI) examination. Through the inclusion and exclusion criteria, 201 patients were finally included. The patients were grouped according to the presence of WMLs and were compared by age, sex, hypertension, diabetes, RLS, and other characteristic data. We observed the MRI fluid attenuation inversion recovery sequence (FLAIR) image and compared the differences in WMLs between the RLS-positive group and the RLS-negative group. There were 71 cases and 130 cases of migraine with and without WMLs, respectively. A statistically significant difference in near-cortical WMLs with RLS in migraine patients was observed (p = 0.007). Logistic regression analysis was adjusted by age, sex, duration of migraine, and severity. Migraine with aura and family history identified the RLS status as the sole determinant for the presence of near-cortical WMLs (OR = 2.69; 95%CI 1.386–5.219; p = 0.003). Near-cortical white matter lesions in migraine patients are related to RLS, especially in the blood supply area of the anterior cerebral artery. This small demyelination of the near-cortical WMLs may be a potential marker for the right-to-left shunt of the heart. Transcranial Doppler ultrasonography may help finding more RLS in migraineurs with near-cortical WMLs.

Background Migraine is a common clinical primary headache with unclear aetiology. In recent years, studies have shown that migraine is related to patent foramen ovale, and some patients with migraine have white matter lesions. However, the relationship among the three is unclear. Objective To explore the characteristics of white matter lesions (WMLs) in migraine patients with patent foramen ovale and to predict the occurrence of patent foramen ovale through magnetic resonance imaging (MRI) characteristics in patients with migraine. Methods Seventy-seven patients clinically diagnosed with migraine were examined by transcranial Doppler ultrasound (cTCD) and MRI. The patients were grouped according to the presence of WMLs, with matching by age, sex, hypertension, diabetes, PFO and other characteristic data. We observed the MRI fluid attenuation inversion recovery sequence (FLAIR) image and compared and analysed the difference in WMLs between the PFO-positive group and the PFO-negative group. Results There were 42 cases and 35 cases of migraine with and without WMLs, respectively. A statistically significant difference in near-cortical WMLs with PFO in migraine patients was observed (P=0.001). Logistic regression analysis adjusted by age, sex, hypertension and diabetes identified PFO status as the sole determinant for the presence of near-cortical WMLs (OR = 0.14; 95%CI 0.045–0.421; p < 0.001) Conclusion Near-cortical white matter lesions in migraine patients are related to PFO. Transcranial Doppler ultrasonography may reveal more PFO in patients with migraine and near-cortical WMLs.

DNAJC7 has recently been recognized as a novel amyotrophic lateral sclerosis (ALS) risk gene. To date, few studies have screened DNAJC7 mutations in Chinese population. Further studies are needed to clarify the clinical and genetic features of DNAJC7-related ALS. Sporadic ALS (sALS) patients and controls were enrolled in this study. Variants were detected by whole-exome sequencing and validated via Sanger sequencing. Gene-based burden analysis was conducted. Potentially damaging variants in DNAJC7 were identified in 3 sALS patients. The frequency of bulbar onset was significantly higher in DNAJC7-related ALS patients than in the whole group. However, burden analysis showed no enrichment of rare DNAJC7 variants in sALS patients. Reported variant N369T showed no significant difference in distribution among different groups. In conclusion, DNAJC7 variants may be associated with ALS but not play a main role in Chinese patients. DNAJC7-related ALS patients tended to have a bulbar onset. Our study supported the pathogenic role of DNAJC7 in ALS and expanded the phenotypic and genetic spectrum of DNAJC7-related ALS.

虽然孕产妇的头痛患病率低于非妊娠期妇女,但头痛仍是孕产妇常见的主诉,根据临床特点及转归,可能表现为以下3种情况:原发性头痛患者出现类似于先前的发作;既往原发性头痛患者出现不同于以往的发作;新发急性头痛[1].第一种情况多提示原发性头痛,如偏头痛和紧张性头痛.后两者需警惕继发性头痛,包括先兆子痫、子痫、脑静脉血栓形成(cerebral venous thrombosis, CVT )、脑出血(intracerebral hemorrhage,ICH)、蛛网膜下腔出血(subarachnoid hemor-rhage, SAH)以及某些类型缺血性卒中、垂体卒中、可逆性脑血管收缩综合征(reversible cerebral vasoconstriction syn-drome, RCVS)、可逆性后部白质脑综合征(posterior reversible encephalopathy syndrome, PRES)等.因生理情况发生改变,孕产妇头痛发病率、临床表现与其他人群存在差异,处理方式也有所不同,尤其是对继发性疾病认识不足,可能导致误诊,延误治疗,对家庭、社会以及法律层面造成严重后果,因此疾病的诊断与治疗非常关键.本文就原发性和继发性头痛相关疾病的流行病学、危险因素、头痛特点及治疗等作一概述,以期提高临床诊治水平.