Abstract Background Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. Methods The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. Conclusions The MOYAOMICS project represents a significant step toward comprehending MMD’s molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.
The precise circuit of the substantia nigra pars reticulata (SNr) involved in temporal lobe epilepsy (TLE) is still unclear. Here we found that optogenetic or chemogenetic activation of SNr parvalbumin+ (PV) GABAergic neurons amplifies seizure activities in kindling- and kainic acid-induced TLE models, whereas selective inhibition of these neurons alleviates seizure activities. The severity of seizures is bidirectionally regulated by optogenetic manipulation of SNr PV fibers projecting to the parafascicular nucleus (PF). Electrophysiology combined with rabies virus-assisted circuit mapping shows that SNr PV neurons directly project to and functionally inhibit posterior PF GABAergic neurons. Activity of these neurons also regulates seizure activity. Collectively, our results reveal that a long-range SNr-PF disinhibitory circuit participates in regulating seizure in TLE and inactivation of this circuit can alleviate severity of epileptic seizures. These findings provide a better understanding of pathological changes from a circuit perspective and suggest a possibility to precisely control epilepsy.
Object: To explore the post-hemispherotomy seizure outcome and its prognostic predictors in children with refractory epilepsy. Methods: We reviewed 83 consecutive children patients with refractory epilepsy who underwent hemispherectomy from June 2014 to January 2017 at our Paediatric Epilepsy Centre. Demographic, clinical, EEG, neuroimaging, and surgical data were collected. Seizure outcome data were collected via outpatient clinics as well as telephone visits and were graded according to Engel criteria. Logistic regression model and Cox proportional hazard regression model were respectively applied to explore the related factors predicting the seizure outcomes of children after hemispherotomy. Results: Of the 83 patients, 55 (63.2%) were male. The mean seizure onset age was 1.9 years (0–8.7 years), and the mean surgery age was 5.0 years (0.8–14.0 years). At a mean follow-up of 3years, 69 children (83.1%) were seizure free, and 14 (16.9%)exhibited seizure recurrence. In a univariate analysis, whether or not considering follow-up time, a nonlateralized interictal EEG pattern, bilateral PET abnormalities and acute postoperative seizures (APOS) all could predict poor seizure outcome after hemispherotomy. Bilateral PET abnormalities were independently correlated with unfavourable seizure outcomes in the multivariate Logistic regression analysis (Odds ratio(OR)=13.05, 95%CI=1.52-112.29, P=0.019) and in the multivariate Cox proportional hazard analysis(OR=13.99, 95%CI=2.75-71.17, P=0.001). Conclusions: Children epileptic patients with bilateral PET abnormalities may have poor seizure outcomes after procedure of hemispherotomy. This study will facilitate better candidate selection for hemispherotomy and early identification of unfavourable seizure outcomes.
Abstract Aims Temporal lobe epilepsy (TLE), often associated with cognitive impairment, is one of the most common types of medically refractory epilepsy. Deep brain stimulation (DBS) shows considerable promise for the treatment of TLE. However, the optimal stimulation targets and parameters of DBS to control seizures and related cognitive impairment are still not fully illustrated. Methods In the present study, we evaluated the therapeutic potential of DBS in the medial septum (MS) on seizures and cognitive function in mouse acute and chronic epilepsy models. Results We found that DBS in the MS alleviated the severity of seizure activities in both kainic acid‐induced acute seizure model and hippocampal‐kindled epilepsy model. DBS showed antiseizure effects with a wide window of effective stimulation frequencies. The antiseizure effects of DBS were mediated by the hippocampal theta rhythm, as atropine, which reversed the DBS‐induced augmentation of the hippocampal theta oscillation, abolished the antiseizure effects of DBS. Further, in the kainic acid‐induced chronic TLE model, DBS in the MS not only reduced spontaneous seizures, but also improved behavioral performance in novel object recognition. Conclusion DBS in the MS is a promising approach to attenuate TLE probably through entrainment of the hippocampal theta rhythm, which may be therapeutically significant for refractory TLE treatment.
We report an 8-year-old boy diagnosed with both CMT1 and narcolepsy, which were not reported simultaneously presenting in one person. The boy presented with a history of increased suddenly falling frequency and excessive daytime sleepiness for 3 months. CMT1 was diagnosed by electrophysiology and genetic testing. Narcolepsy had not been diagnosed until the frequently falling caused by sudden and transient episodes of legs weakness triggered by emotion was found. Multiple sleep latency test showed multiple sleep onset REM periods with reduced sleep latency. When CMT1 and narcolepsy were coexist in an individual, the latter might be overlooked. Cataplexy caused by narcolepsy might be disregard as distal muscle weakness of CMT1. The daytime sleepiness might also be ignored. Therefore, we recommend that patients with sleep disorders should be queried about the symptoms of narcolepsy.
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