It is estimated that approximately one-third of epilepsy patients are affected by drug resistance. After 2 appropriately used antiseizure medications have failed to control seizures, patients should be referred to a comprehensive epilepsy center for re-evaluation and targeted treatment whenever possible. Patients with a clear cause should receive treatment targeted at the cause of epilepsy; patients without a clear cause should consider the feasibility of epilepsy surgery and other treatments as early as possible. Substantial evidence shows that delaying the effective treatment may adversely affect the clinical outcomes and increase the risk of cognitive impairment, other comorbidities, and premature death. Research on the mechanisms of drug resistance and new drug development in epilepsy is progressing rapidly, and new treatment methods, including disease-modifying therapies, are promising.

Objective:To explore the clinical manifestations, auxiliary examinations, treatment, and outcomes of autoimmune-associated epilepsy (AAE) with anti-glutamic acid decarboxylase 65 (GAD65) antibodies.Methods:Nine patients diagnosed with AAE with anti-GAD65 antibodies between July 2019 and December 2023 at the Department of Neurology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, were enrolled. Their clinical data and prognosis were retrospectively analyzed.Results:The onset age of these 9 cases was 13.0-59.0 (29.0±13.4) years, with 8 females and 1 male. The main clinical phenotypes at onset included limbic encephalitis/extralimbic encephalitis (6 cases) and chronic epilepsy (3 cases, of whom 1 case was accompanied with stiff person syndrome). The former often demonstrated T 2/fluid attenuated inversion recovery (FLAIR) hyperintensities and enlargement of hippocampus and amygdala (5 cases), and may present with concomitant meningoencephalitis (2 cases) or hypertrophic pachymeningitis (1 case). The latter showed normal (2 cases) or increased T 2/FLAIR signals in the hippocampal tails (1 case) in magnetic resonance imaging. Electroencephalogram findings were usually characterized by slow activities (6 cases) and temporal epileptiform discharges (6 cases). Five cases concurrently presented with one or more other autoimmune diseases, including the autoimmune polyendocrine syndrome type Ⅱ in 1 case. All cases received first-line immunotherapy and 7 cases received long-term immunosuppressive agents. Eight cases were followed up for 5-45 months and 2 cases experienced relapse of autoimmune encephalitis (presented with new-onset seizures). At the last follow-up, all cases achieved favourable outcomes according to the modified Rankin Scale scores (all≤2) and 4 patients had reduced seizures, of whom 2 were seizure-free. Conclusions:Anti-GAD65 antibody-positive AAE is mainly composed of postencephalitic epilepsy and chronic temporal lobe epilepsy. The co-occurrence of systemic autoimmune diseases is common, and meningeal lesions sometimes can be involved in MRI findings. Patients usually have poor response to immunotherapy and anti-seizure medication,and some postencephalitic epilepsy patients who receive early immunotherapy and long-term immunosuppressants can achieve sustained seizure freedom.

Cerebral amyloid angiopathy(CAA)is one of the cerebral small vessel diseases in which amyloid-β is deposited in the cortical,subcortical and leptomeningal arterioles.The disease is commonly encountered in the elderly,characterized by recurrent lobar hemorrhage and cognitive dysfunction.In recent years,the diversity of intestinal microbiota and its products have been reported to be involved in the pathogenic process of central nervous system diseases through various pathways such as neuroinflammation and blood brain barrier leakage.However,the underlying mechanism of intestinal microbiota in CAA is not clear.It has been reported that intestinal microbiota disorder can induce intracranial Aβ production and aggregation,blood-brain barrier leakage,and Aβ transport receptor imbalance,and then damage in blood vessels,accompanied by neuroinflammatory mechanisms.The authors reviewed the potential mechanism of intestinal microbiota involved in amyloid deposition to provide a theoretical reference for the exploration of potential clinical therapeutic targets for CAA.

Middle Aged ; Humans ; Siblings ; Mutation ; TATA-Binding Protein Associated Factors/genetics*

Objective:To evaluate the status and influencing factors of psychiatric comorbidities of patients with epilepsy (PWEs) in Hubei province during the outbreak of COVID-19.Methods:From February 23, 2020 to March 5, 2020, a network questionnaire survey (including demographic characteristics, seizures, Generalized Anxiety Disorder Scale-7 score, Patient Health Questionnaire-9 score, Insomnia Severity Index score) was conducted among 570 PWEs who visited the Epilepsy Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology during April 1, 2019 and January 20, 2020. SPSS 22.0 software was used for correlation analysis of sociodemographic characteristics, epilepsy related factors, perceived threat to the COVID-19 and psychiatric comorbidity (depression, anxiety and insomnia) of PWEs during the COVID-19 epidemic.Results:A total of 362 valid questionnaires were included for analysis (the response rate was 63.51%,362/570). Thirty-four (9.4%), forty-seven (13.0%) and seventy-one (19.6%) patients suffered from anxiety, depression and insomnia, respectively. Patients with seizure frequency ≥2 times/month before the epidemic ( OR=3.395,95% CI 1.561-7.384, P=0.002), poor subjective quality of life during the epidemic ( OR=10.753,95% CI 1.938-59.654, P=0.024), and moderate to severe worry about bad impact of the epidemic on epilepsy ( OR=3.077, 95% CI 1.382-6.853, P=0.006) were more likely to be anxious. Patients with poor subjective quality of life during the epidemic ( OR=6.188, 95% CI 1.317-29.079, P=0.021) were more likely to be depressed. Patients with COVID-19 related symptoms ( OR=3.609, 95% CI 1.674-7.778, P=0.001), children ( OR=3.090, 95% CI 1.759-5.431, P<0.001), seizure frequency ≥2 times/month before the epidemic ( OR=1.907, 95% CI 1.017-3.575, P=0.044), and moderate to severe worry about unanticipated seizures ( OR=2.555, 95% CI 1.370-4.764, P=0.003) were more likely to suffer from insomnia. Conclusions:During the COVID-19 epidemic, parts of PWEs suffered from anxiety, depression and insomnia. PWEs with poor subjective quality of life, high frequency of epileptic seizures before the epidemic, excessive worry about bad impact of the epidemic on epilepsy and excessive worry about unanticipated seizures were prone to anxiety, depression and insomnia.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare type of paroxysmal dyskinesia with a population estimated incidence of 1/150, 000. PKD is likely correlated with genetics. Genetic studies have shown that, in addition to PRRT2 gene, mutations in SCN8A, KCNA1, CHRNA4, DEPDC5, PNKD, SLC2A1, KCNMA1, ADCY5 and other genes could also lead to PKD phenotypes. Functional imaging studies have found that PKD patients have subtle structural or functional abnormalities in the cortex, basal ganglia and thalamus. This paper reviews the recent advances in genetics and functional imaging of PKD, aiming at helping us to further understand the underlying pathophysiological mechanisms of PKD.

Objective:To design and compile quality evaluation questionnaire on problem-based learning (PBL) of Neurology and to test its reliability and validity.Methods:Referring to the framework of the evaluation system and according to the characteristics of the discipline, we designed the questionnaire on PBL of Neurology. The clinical medical students who participated in neurologic PBL course were taken as the objects of investigation. The reliability of the questionnaire and the reliability of internal consistency were tested. Correlation analysis and exploratory factor analysis were used to evaluate the validity of the questionnaire.Results:The questionnaire on PBL of Neurology included three first-level indicators: teaching plan quality evaluation, teaching method evaluation and teaching quality evaluation, containing 6 second-level indicators and 25 third-level indicators. The correlation coefficient ρ=0.990 ( P<0.01) showed that the retest reliability was good. The cronbach's α coefficient is 0.901, meeting the internal consistency reliability requirement. And the content validity correlation coefficient was 0.307-0.7 ( P<0.05), indicating that each third-level index had a significant correlation with the total score, and the questionnaire item design was good. The three first-level indicators were used as common factors to evaluate the structural validity by exploratory factor analysis and identify the direction of optimization. Conclusion:The questionnaire has good reliability and validity, which can be used as a tool for scientific evaluation on PBL of neurology, and also provide an optimization direction for further research in the future.

Spontaneous intracerebral hemorrhage (ICH) continues to be associated with the highest mortality and morbidity of all forms of stroke. Early identification and management of ICH is crucial. Blood pressure control, care in a dedicated stroke unit, identification of secondary etiologies, reversal of associated coagulopathy, and neurosurgical management, when indicated, are essential to optimizing outcomes.

Great improvements have been made in diagnosis and treatment of intracerebral hemorrhage in recent years. Chinese guidelines for diagnosis and treatment of intracerebral hemorrhage 2019 are published by Chinese Society of Neurology and Chinese Stroke Society in this issue of Chinese Journal of Neurology. The purpose of the guideline is to provide up-to-date recommendations in management of acute intracerebral hemorrhage, especially etiological classification, hematoma enlargement, anti-hypertension, surgicalized treatment, prevention of deep venous thrombosis,and intracerebral hemorrhage recurrence, etc. The principle of individualized treatment on the basis of guideline is emphasized.

Objective To investigate the time course of cerebral infarction with diffusion kurtosis imaging-related parameters.Methods According to the time interval from symptom onset to MRI examination, 114 cases of cerebral infarction were divided into five groups:8 cases of hyperacute phase(less than 6 hours), 14 cases of acute(>6-24 h), 60 cases of early subacute(>24 h-7 d), 20 cases of late subacute(>7-14 d), and 12 cases of chronic phase ( >14 d-2 months).They underwent routine diffusion weighted imaging (DWI) and diffusion kurtosis imaging (DKI) scanning, and apparent diffusion coefficient ( ADC) and DKI-derived parameters were obtained from them.The derived diffusion parameters were compared among different phases in the patients , and the percent of changes in the infarcted regions were calculated.Paired t-test was used to compare the difference of each parameter between the infarcted region and contralateral normal region , and their correlation with time interval was tested using Pearson correlation analysis.Results Except for chronic phase , mean kurtosis ( MK) , axial kurtosis ( K∥) , radial kurtosis (K⊥)map showed uneven high signal in the infarcted regions , while mean diffusion(MD), axial diffusion(D∥), radial diffusion(D⊥) showed uniform low signal.MK values in the infarcted regions of hyperacute, acute, early subacute and late subacute phase (1.331 ±0.357,1.578 ±0.453,1.519 ±0.455, 1.403 ±0.275 ) increased significantly , compared with the contralateral normal mirror regions ( 0.850 ± 0.236,0.827 ±0.194,0.865 ±0.144,0.939 ±0.212) (t values were 5.242,6.907,12.416,5.629, respectively.P values were all less than 0.01 ).MK, K∥, K⊥ achieved a peak in the acute and early subacute phase , and showed more amplitude than the decrease of MD , D∥, D⊥.Then they gradually reduced, and tended to normalize.MK, MD, ADC had a significant correlation with the time onset of cerebral infarction ( r was 0.354, 0.747, 0.723, respectively, P values were all less than 0.05 ).Conclusion Diffusion kurtosis imaging can provide more diffusion information than conventional DWI , which can better reflect the microstructure changes in tissue.