Overlapping cortical malformations in patients with pathogenic variants in GRIN1 and GRIN2B.

BACKGROUND: Malformations of cortical development (MCDs) have been reported in a subset of patients with pathogenic heterozygous variants in GRIN1 or GRIN2B, genes which encode for subunits of the N-methyl-D-aspartate receptor (NMDAR). The aim of this study was to further define the phenotypic spectrum of NMDAR-related MCDs. METHODS: We report the clinical, radiological and molecular features of 7 new patients and review data on 18 previously reported individuals with NMDAR-related MCDs. Neuropathological findings for two individuals with heterozygous variants in GRIN1 are presented. We report the clinical and neuropathological features of one additional individual with homozygous pathogenic variants in GRIN1. RESULTS: Heterozygous variants in GRIN1 and GRIN2B were associated with overlapping severe clinical and imaging features, including global developmental delay, epilepsy, diffuse dysgyria, dysmorphic basal ganglia and hippocampi. Neuropathological examination in two fetuses with heterozygous GRIN1 variants suggests that proliferation as well as radial and tangential neuronal migration are impaired. In addition, we show that neuronal migration is also impaired by homozygous GRIN1 variants in an individual with microcephaly with simplified gyral pattern. CONCLUSION: These findings expand our understanding of the clinical and imaging features of the 'NMDARopathy' spectrum and contribute to our understanding of the likely underlying pathogenic mechanisms leading to MCD in these patients.

Cognitive dysfunction and event-related potentials in patients with chronic fatigue syndrome / 中华行为医学与脑科学杂志

Cognitive dysfunction,as a common symptom among patients with chronic fatigue syndrome (CFS) and patients with fibromyalgia(FM),impacts on life quality,occupation and study of these patients.However,the neural correlates to the cognitive impairment are unknown.Event related potentials,which reflect the information processing objectively and constantly,provide possibility for taking a insight into and estimating the dysfunction.By summarizing and analyzing studies in event related potentials about chronic fatigue syndrome,fibromyalgia,we found that CFS patients were characterized with prolonged latency of N200 and P300 accompanied by decreased P300 amplitude when they performed on Oddball paradigm,fibromyalgia patients were characterized with lower P300 amplitude when they concentrated on Oddball task,meanwhile,fibromyalgia patients also showed decreased P100/N100,P200,P300,LPC in emotional word decision task and somatic pictures decision task.It's suggests that the cognitive dysfunction in CFS is mainly caused by slowed speed of information identification and classification,whereas in FM it's dysregulation in attention control system results in the cognitive dysfunction.Limitations in current studies and prospects on researches about cognitive dysfunction in CFS for future were also discussed.

Effect of dexmedetomidine on synaptic transmission in spinal dorsal horn of rats / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on synaptic transmission in the spinal dorsal horn of rats.Methods Male Sprague-Dawley rats,aged 4-6 weeks,weighing 150-200 g,were used in the study.The lumbar enlargemnent segments of the spinal cord were harvested,and the parasagittal lumbosacral spinal cord slices with attached dorsal roots were prepared and incubated in artificial cerebro-spinal fluid.The whole-cell patch-clamp technique was used to record each index,and 4 spinal cord slices were selected and used for each index records.Experiment Ⅰ Dexmedetomidine was added cumulatively in concentration increments.Aδ and C fibers-mediated evoked excitatory postsynaptic currents (eEPSCs) were recorded before administration (baseline) and during perfusion with dexmedetomidine 4 and 10 μg/ml.Experiment Ⅱ The neurons innervated by Aδ and C fibers were selected,and Aδ and C fibers-mediated eEPSCs were recorded before administration (baseline),at 5 min of perfusion with yohimbine (alpha 2 adrenergic receptor antagonist) 2 μmol/L,and during continuous perfusion with yohimbine 2 μmol/L plus dexmedetomidine 4 μg/ml.Experiment Ⅲ The evoked excitatory postsynaptic potentials (eE-PSPs) and evoked inhibitory postsynaptic potentials (eIPSPs) were recorded before administration (baseline) and during perfusion with dexmedetomidine 4 μg/ml.Results Dexmedetomidine could dose-dependently inhibit Aδ and C fibers-mediated eEPSCs,dexmedetomidine could inhibit Aδ and C fibers-mediated eEPSPs and produced no effect on eIPSPs,and yohimbine could inhibit dexmedetomidine-induced inhibitory effect on eEPSCs.Conclusion The mechanism by which dexmedetomidine inhibits nociceptive information transmission in the spinal dorsal horn is related to inhibition of excitatory synaptic transmission through activating α2-adrenergic receptors,but not related to activation of inhibitory synaptic transmission in rats.