Case data were collected from an adult patient with sporadic neuronal intranuclear inclusion disease who were diagnosed in Affiliated Hospital of Jining Medical University. The patient was an elderly woman aged 64 years， with the main clinical manifestations of limb tremor and paroxysmal disturbance of consciousness. Skin biopsy of the patient showed the presence of eosinophilic inclusion bodies， head MRI diffusion sequences showed abnormal hyperintensity signals in the corticomedullary junction area， and genetic testing showed pathogenic genes NOTCH2NLC positive. The patient was diagnosed with neuronal intranuclear inclusion disease and was given symptomatic treatment. This case report suggests that for patients with limb tremor or paroxysmal disturbance of consciousness， if MRI diffusion sequences show abnormal hyperintensity signals in the corticomedullary junction area， the possibility of this disease should be considered， and skin biopsy and genetic testing should be performed to make a confirmed diagnosis， in order to provide early treatment.

MELAS syndrome is a genetic disease caused by mutations in mitochondrial DNA(mtDNA)or nuclear DNA.Eighty percent of the cases are caused by m.3243A>G mutation.Heteroplasmy,defined as the presence of both normal and mutant mtDNA in cells,is related with the severity of MELAS syndrome.This article reviews the research in mtDNA heterogeneity related to MELAS syndrome,aiming to provide an insight into new therapies for the syndrome.

Background::Given that seizures may be triggered by vaccination, this study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy (PWE) after being vaccinated against coronavirus disease 2019 (COVID-19).Methods::This study retrospectively enrolled PWE who were vaccinated against COVID-19 in the epilepsy centers of 11 hospitals in China. We divided the PWE into two groups as follows: (1) patients who developed seizures within 14 days of vaccination were assigned to the SAV (with seizures after vaccination) group; (2) patients who were seizure-free within 14 days of vaccination were assigned to the SFAV (seizure-free after vaccination) group. To identify potential risk factors for seizure reccurence, the binary logistic regression analysis was performed. Besides, 67 PWE who had not been vaccinated were also included for elucidating the effects of vaccination on seizures recurrence, and binary logistic regression analysis was performed to determine whether vaccination would affect the recurrence rate of PWE who had drug reduction or withdrawal.Results::The study included a total of 407 patients; of which, 48 (11.8%) developed seizures within 14 days after vaccination (SAV group), whereas 359 (88.2%) remained seizure-free (SFAV group). The binary logistic regression analysis revealed that duration of seizure freedom ( P < 0.001) and withdrawal from anti-seizure medications (ASMs) or reduction in their dosage during the peri-vaccination period were significantly associated with the recurrence of seizures (odds ratio= 7.384, 95% confidence interval = 1.732–31.488, P = 0.007). In addition, 32 of 33 patients (97.0%) who were seizure-free for more than three months before vaccination and had a normal electroencephalogram before vaccination did not have any seizures within 14 days of vaccination. A total of 92 (22.6%) patients experienced non-epileptic adverse reactions after vaccination. Binary logistic regression analysis results showed that vaccine did not significantly affect the recurrence rate of PWE who had the behavior of ASMs dose reduction or withdrawal ( P = 0.143). Conclusions::PWE need protection from the COVID-19 vaccine. PWE who are seizure-free for >3 months before vaccination should be vaccinated. Whether the remaining PWE should be vaccinated depends on the local prevalence of COVID-19. Finally, PWE should avoid discontinuing ASMs or reducing their dosage during the peri-vaccination period.

The brain is an important organ in the human body with high metabolic requirements, and epilepsy, as a common neurological disease, also exhibits high metabolic characteristics in its lesion area. At present, controlling seizures caused by drug-resistant epilepsy or specific metabolic defects through metabolic regulation has shown good anti epileptic effects. In recent years, people have become increasingly interested in the relationship between brain metabolism and epileptic seizures. So far, several new anti epileptic therapies targeting metabolic pathways have been proposed, including inhibition of glycolysis, targeted lactate dehydrogenase, and dietary therapy. It is highly promising to intervene in epilepsy by regulating brain metabolism, but currently we still lack a thorough understanding of the role of brain metabolism in controlling epilepsy. This review aims to gain a deeper understanding of energy metabolism in the brain and its correlation with epilepsy, emphasizing the regulation of neuronal excitability through glycolysis, in order to search for effective anti epileptic therapies, in order to better understand the role of glycolysis in epileptic seizures and reveal potential therapeutic targets for epilepsy.

Molecular imaging is a developing research field and it has become a research hotspot.It integrates molecular biochemistry, data processing, nanotechnology, image processing and other technologies and has high specificity, high sensitivity, and high image resolution.It can provide qualitative, positioning, and quantitative data for clinical diagnosis.Clinically, 30% of epileptic patients develop into intractable epilepsy, but magnetic resonance imaging(MRI) can not detect structural lesions.These patients need accurate positioning in order to improve the effectiveness of epilepsy surgery.Because the current preoperative positioning methods have certain limitations, some epileptic patients still have recurrent seizures after the operation.Therefore, researchers continue to explore targeted tracers with high specificity and strong sensitivity.Various nanotechnology and functional magnetic resonance imaging methods are used to study the accurate localization methods of epilepsy.This paper summarized and analyzed the latest research of molecular imaging technology in China and abroad, such as the latest research of single photon emission computed tomography(SPECT) and positron emission tomography(PET) molecular imaging, the application of various nanotechnology combined with functional magnetic resonance in the accurate diagnosis and treatment of epilepsy, and various targeted tracers that haven been developed at present.The results suggest that the continuous improvement of quantitative image analysis, the integration of multi-mode imaging, the development of PET radioactive tracers, and the combination of nanotechnology and functional magnetic resonance imaging(fMRI) will facilitate a more comprehensive understanding of the pathophysiological mechanism of epilepsy.It is promising to realize the accurate diagnosis and treatment of intractable epilepsy.

Objective To investigate the effect of microRNA-22 (miRNA-22) on the expression of P2X7 receptor and inflammatory factors in hippocampus of rats with epilepsy. Methods Healthy SD male rats were intraperitoneal injected with lithium chloride and pilocarpine to induce epilepsy. Three days later, 45 epileptic rats were randomly divided into three groups: epilepsy group( EP group), miRNA-22 agomir group (EF+agomir group) and miRNA-22 agomir control group ( EF+agomir control group). Another 15 healthy rats were selected as control group(N group). The expression of P2X7 protein was detected by West- ern blot and the levels of miRNA-22, P2X7 mRNA, NF-κB mRNA ,IL-1β mRNA were detected by qRT-PCR. Nissl staining was used to observe the damage of Nissl bodies. Results Western blot result showed that compared with the N group(0. 91±0. 10), the level of P2X7 protein in EP group (1. 17±0. 052) in-creased, and the difference was statistically significant (t=-4. 11,P=0. 02). Compared with the EP+ag-omir control group(0. 94± 0. 14),the expression of P2X7 protein in EP+agomir group (0. 66± 0. 06) de-creased and the difference was significant (t=-3. 10,P=0. 04). And the qRT-PCR results showed that compared with N group, the levels of P2X7mRNA (9. 08±0. 94), NF-κB mRNA (20. 10±2. 15) and IL-1β mRNA (50. 64±5. 42) in EP group increased(t=-14. 96,P<0. 05; t=-15. 38,P<0. 05; t=-15. 87,P<0. 05). The expression of P2X7mRNA (1. 31 ± 0. 64), NF-κB mRNA ( 2. 28 ± 1. 10) and IL-1β mRNA (2. 12±1. 20) in EF+agomir group decreased compared with EP group((9. 08± 0. 94),( 20. 10± 2. 15), (50. 64±5. 42)) and EF+agomir control group((7. 03 ±1. 90),(18. 72±1. 76),(47. 39±6. 16)), and the differences were statistically significant(F=29. 77, P<0. 01;F=98. 99, P<0. 05;F=96. 29, P<0. 01). Nissl staining results showed that a large number of morphologically abnormal and disintegrated Nissl bodies could be observed in the hippocampal CA1 and CA3 regions of EP group,which showed a smaller size,irreg-ular morphology,chromatin pyknosis,boundary blur between nucleus and cytoplasm. Compared with the nor-mal group, the difference was significant (P<0. 05). While in miRNA-22 agomir group, the disintegration of Nissl bodies was improved and the number of Nissl bodies increased. Conclusion Intraventricular injec-tion of miRNA-22 agomir can down-regulate the expression of P2X7 receptor and related inflammatory factors in hippocampus of epileptic rats, thus inhibiting seizures.

Objective To investigate the optimal initial concentration of microRNA22 agomir in epilepsy model induced by lithium chloride-pilocarpine after single injection of lateral ventricle.Methods 36 rats with acute temporal lobe epilepsy were randomly divided into 6 groups:the control group and the other five groups were the experimental group.All epilepsy rats were selected for right lateral ventricle injection.The control group was given negative control reagent,while the experimental group were given 0.1 mmol/L,2.5 mmol/L,5 mmol/L,10 mmol/L,20 mmol/L different concentrations of miRNA22agomir reagent.6 rats in each group were randomly selected for acute phase experiment after 3 days of administration.The expression of P2X7 in hippocampus of epilepsy rats was determined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR).Results Compared with control group,the protein and mRNA expression of P2X7 reduced in all of the model group.The protein and mRNA expression level of P2X7 protein in hippocampus of rats injected with 2.5 mmol/L,5 mmol/L and 10 mmol/L in each experimental group were significantly lower than that in the other two groups (P ＜ 0.05).Moreover,the protein and mRNA expression level of P2X7 were the lowest at 2.5 mmol/L injection and 10 mmol/L,and there was no significant difference between the two groups (P ＞ 0.05).Conclusions The optimal onset concentration for unilateral lateral ventricle injection miRNA22 agomir treatment of temporal lobe epilepsy is 2.5 mmol/L.

Objective To investigate the phenotypes and genetics of an early-onset familial Alzheimer′s disease ( EO-FAD ) family.Methods The clinical manifestations , brain MRI results and neuropathological findings of the proband and pedigree members of the EO -FAD family were evaluated. Autopsy was performed in the proband . Results Fifteen members of this family had a presenilin 1 (PSEN1) p.G378E mutation and nine of them had clinical manifestations or the MRI changes of EO -FAD. Neuropathological findings from autopsy of the proband disclosed moderate cortical atrophy throughout the brain, especially in frontal lobe and temporal lobe .Neuronal loss with gliosis was observed in the cortices of the frontal, temporal and occipital lobes , as well as in parahippocampal gyrus .Numerous senile plaques and neurofibrillary tangles were present in the cerebral cortex .The proband′s younger sister showed similar clinical presentations and MRI changes , and other members of this family demonstrated progressive memory loss.Conclusion A p.G378E mutation in the PSENl gene was identified in a Chinese EO-FAD pedigree.

Objective To determine the expression profile of serum microRNAs(miRNAs) in early-onset familial Alzheimer's disease (EO-FAD) patients. methods miRNA microarrays were performed to detect the expression profile of serum miRNAs in 2 cases of EO-FAD patients,2 cases of EO-FAD carriers and 2 cases of normal controls.Preliminary bioinformatic analysis was conducted. Result sIt was found that 21 miRNAs were up-regulated and 22 miRNAs were down-regulated in serum of EO-FAD patients,the differences were statistically significant(P<0.05).miR-5704(P=0.0002),miR-4639-3p(P=0.0195),miR-107(P=0.0204) were markedly up-regulated,miR-5572(P=0.0008),miR-204-3p(P=0.0014),miR-542-5p(P=0.0106) and miR-155-5p(P=0.0240) were markedly down-regulated.Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the dysregulated miRNAs may be involved in the mechanism of EO-FAD by affecting neurotrophin signaling pathway.Conclusion miR-5704,miR-4639-3p,miR-107,miR-5572,miR-204-3p,miR-542-5p and miR-155-5p may be used as potential biomarkers of EO-FAD,and involved in the mechanism of EO-FAD by affecting neurotrophin signaling pathway.

Objective To investigate the optimal scan time of MRI using the imaging probe alphamethyl-L-tryptophan(α-MTrp)-superparamagnetic iron oxide nanoparticles (SPIONs) for localizing temporal lobe epilepsy (TLE) foci.Methods α-MTrp-SPIONs were injected into rat models of TLE through the tail vein during the acute and chronic stages (72 h and 8 weeks after status epilepticus,respectively).MRI was performed before and 1,2,4,8,24 h after the injection in all animals,and the T2 values of the epileptogenic regions were measured.One-way repeated measures analysis of variance was used for data analysis.Results Compared with the T2 values before the injection of α-MTrp-SPIONs,the T2 signal of epileptogenic regions after the injection had a negative increased change.The T2 values before and 1,2,4,8,24 h after the injection in acute stage were 112.08±5.85,107.83±6.59,105.08±6.79,95.58±5.14,100.92± 5.81,105.17±6.31 respectively,and those in chronic stage were 112.08±7.53,107.75±7.10,102.75± 5.50,96.17±5.01,97.75±4.37,102.92±4.74.The T2 values after the injection were significantly different from those before the injection (both P＜0.01).The T2 value at 4 h after the injection decreased mostly.Conclusions α-MTrp-SPIONs can precisely localize epileptogenic regions of TLE on MRI.The optimal scan time is 4 h after the injection.