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.

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.

Background: Systematically assessing the causal associations between medications and neurodegenerative diseases is significant in identifying disease etiology and novel therapies. Here, we investigated the putative causal associations between 23 existing medication categories and major neurodegenerative diseases (NDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Methods: A two-sample mendelian randomization (MR) approach was conducted. Estimates were calculated using the inverse-variance weighted (IVW) method as the main model. A sensitivity analysis and a pleiotropy analysis were performed to identify potential violations. Results: Genetically predisposition to antihypertensives (OR = 0.809, 95% CI = 0.668–0.981, p = 0.031), thyroid preparations (OR = 0.948, 95% CI = 0.909–0.988, p = 0.011), and immunosuppressants (OR = 0.879, 95% CI = 0.789–0.979, p = 0.018) was associated with a decreased risk of AD. Genetic proxies for thyroid preparations (OR = 0.934, 95% CI = 0.884–0.988, p = 0.017), immunosuppressants (OR = 0.825, 95% CI = 0.699–0.973, p = 0.022), and glucocorticoids (OR = 0.862, 95% CI = 0.756–0.983, p = 0.027) were causally associated with a decreased risk of PD. Genetically determined antithrombotic agents (OR = 1.234, 95% CI = 1.042–1.461, p = 0.015), HMG CoA reductase inhibitors (OR = 1.085, 95% CI = 1.025–1.148, p = 0.005), and salicylic acid and derivatives (OR = 1.294, 95% CI = 1.078–1.553, p = 0.006) were associated with an increased risk of ALS. Conclusions: We presented a systematic view concerning the causal associations between medications and NDs, which will promote the etiology discovery, drug repositioning and patient management for NDs.