Plasma lipid profiles and homocysteine levels in anti-N-methyl-D-aspartate receptor encephalitis.

Introduction: We aimed to investigate whether lipid profiles and homocysteine levels in patients with anti-N-methyl-D-aspartate receptor encephalitis are related to clinical presentation and prognosis, which may contribute to further research on the pathogenesis and treatment of this disease. Methods: This study included a total of 43 patients with anti-N-methyl-D-aspartate receptor encephalitis and 43 sex-age-matched healthy controls. Baseline demography, clinical data, patient outcomes, and ancillary examination results were recorded. Patients were followed up every 2-3 months during the first year. The modified Rankin Scale score was used to evaluate the therapeutic effect and clinical outcome. Results: Among the 43 patients included in this study, 55.81% were male, the mean age of onset was 27 years old, and the median modified Rankin Scale score on admission was 3.0. Apolipoprotein A-1 was significantly lower in patients with anti-N-methyl-D-aspartate receptor encephalitis compared with healthy controls (p = 0.004). Compared with healthy controls, homocysteine (p = 0.002), apolipoprotein B (p = 0.004), Lpa (p = 0.045), and apolipoprotein B/apolipoprotein A-1 (p = 0.001) were significantly increased in patients with anti-N-methyl-D-aspartate receptor encephalitis. According to the modified Rankin Scale scores, 6 months after discharge, 72.09% of patients had a good prognosis and 27.91% had a poor prognosis. In the good prognosis group, age (p = 0.031), lipoprotein a (p = 0.023), apolipoprotein A-1 (p = 0.027) at baseline, and the modified Rankin Scale score on admission (p = 0.019) were significantly higher than those in the poor prognosis group. Conclusion: This study suggests the possibility that serum lipid profile and homocysteine play an important role in the pathogenesis of anti-N-methyl-D-aspartate receptor encephalitis, providing support for lipid-lowering treatment of anti-N-methyl-D-aspartate receptor encephalitis patients.

Characteristics and Prognosis of Autoimmune Encephalitis in the East of China: A Multi-Center Study.

Objective: This study aimed to investigate epidemiological characteristics, clinical manifestations, and long-term outcomes of patients with autoimmune encephalitis (AE) in the east of China. Methods: From January 2015 to December 2019, 226 potential AE patients were recruited from five clinical centers, and a total of 185 patients who met the diagnostic criteria were included in the study. We retrospectively reviewed clinical features, auxiliary examinations, details of treatments, and outcomes of AE, and identified risk factors of poor prognosis. Modified Rankin Scale scores were used to evaluate neurological function, and scores of 3-6 indicated a poor-prognosis. Results: Patients with five main subtypes of AE were enrolled in the study, as follows: anti-NMDAR (79), anti-LGI1 (55), anti-CASPR2 (30), anti-GABABR (16), and anti-AMPAR (5). Among 185 patients, 58.38% (108/185) were male and 41.62% (77/185) were female. The median age at disease onset was 41 years (interquartile range, 17-62). The most common clinical manifestations of AE were seizures (146, 78.92%) and memory deficit (123, 66.49%). A total of 95 (51.35%) patients had abnormal brain magnetic resonance imaging results. Electroencephalographic findings were abnormal in 131 (70.81%) patients, and 168 (90.81%) and 26 (14.05%) patients were treated with first- and second-line immunotherapies, respectively. All surviving patients were followed-up for at least 1 year (range 12-36 months). Good clinical outcomes were achieved in 117 (63.24%), while 68 (36.76%) patients had a poor prognosis. Further, 33 (17.84%) patients relapsed and 10 (5.41%) died within 1 year post-discharge. Older patients tended to have a poorer prognosis, and the occurrence of mental behavioral disorders, movement disorders, disturbance of consciousness, central hypoventilation, and tumors were overrepresented in the poor-prognosis group. Conclusions: AE is a treatable disease, and most patients have a good prognosis. There are differences in the clinical manifestations of patients with different AE subtypes. Some with AE will relapse, and long-term follow-up is of great significance for further research.

Clinical Review and Prognostic Analysis of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionate Receptor-Associated Encephalitis.

Purpose: Autoimmune encephalitis (AE) is a heterogeneous neurological autoimmune disorder associated with cognitive and psychiatric symptoms. It can be divided into several subtypes based on autoantibodies. Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis (AMPAR-E) is one of the recently discovered AE subtypes, usually manifesting limbic encephalitis and with a good prognosis. Considering AMPAR-E has been described for the first time, only a few cases with similar antibodies have been reported clinically. We aimed to clarify the clinical course and prognosis of the disease in the light of previous reports. Patients and Methods: We collected data on the diagnosis and treatment of six cases of AMPAR-E, diagnosed at the Qilu Hospital of Shandong University in the past 5 years. We retrospectively analyzed the clinical characteristics of the patients and performed a follow-up of the disease. Results: The patients often presented with limbic encephalitis, which sometimes coexisted with tumors. In addition, immunotherapy had a significant effect on the disease. The clinical outcome was related to factors such as the age of onset, timing of treatment, and presence of tumors. Conclusion: In conclusion, specific antibody tests should be performed as early as possible in suspected cases. Clinicians should actively administer immunotherapy and the management of the co-tumor. In addition, repeat antibody tests and image examinations following discharge from the hospital guide the maintenance protocol of immunotherapy.

Clinical characteristics and elevated ProGRP and positive oligoclonal bands of 13 Chinese cases with anti-GABABR encephalitis.

OBJECTIVE: To improve the clinical understanding of anti-gamma-aminobutyric-acid B receptor encephalitis (anti-GABABR encephalitis) by analyzing 13 cases. METHODS: We retrospectively studied demographic and clinical features including clinical symptoms, serum/cerebrospinal fluid (CSF) laboratory findings (including antibody test), brain magnetic resonance imaging (MRI), electroencephalogram (EEG), treatment plan, and treatment effect for 13 patients with a definitive diagnosis of anti-GABABR encephalitis. RESULTS: Seven patients (53.8%, 7/13) were complicated with lung cancer. Epileptic seizures were the most common symptoms at onset in 11 patients (84.6%, 11/13). All patients had seizures in the course of the disease. Abnormalities in craniocerebral MRI examination, including hippocampus, occipital lobe, insular lobe, were found in six of nine tested patients, and EEG abnormalities were found in seven out of nine tested patients. Elevated pro-gastrin releasing peptide (ProGRP) levels were found in 70% of patients with a median value of 490.10 pg/ml; and CSF oligoclonal bands were positive for 4 of 10 tested cases. However, there were no significant differences in modified Rankin Scale (mRS) between the ProGRP or CSF oligoclonal band positive and negative groups at admission and follow-up (p > .05). The value between SCLC and non-SCLC subgroup was significantly different (p < .05). Ten patients received immunotherapy (three patients refused treatment). After immunotherapy, the frequency of seizures was significantly reduced. There was a significant difference in mRS between admission and after treatment (p < .05). The average survival time after onset was 27.7 months. CONCLUSIONS: Epilepsy is the most common clinical manifestation of Anti-GABABR encephalitis. The prognosis of anti-GABABR encephalitis is poor. Section of anti-GABABR encephalitis patients have higher level of serum ProGRP and positive GSF oligoclonal bands. Elevated ProGRP or positive CSF oligoclonal bands with classic clinical features can potentially help to improve early recognition of anti-GABABR encephalitis.

Clinical Features and Long-Term Outcomes of Anti-Leucine-Rich Glioma-Inactivated 1 Encephalitis: A Multi-Center Study.

PURPOSE: To describe the clinical manifestation, immunotherapy, and long-term outcomes of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis. PATIENTS AND METHODS: This study was a retrospective analysis of 117 patients with a diagnosis of anti-LGI1 encephalitis identified from the databases of multiple clinical centers between September 2014 and December 2019. The clinical features, ancillary test results, and details of long-term outcomes were evaluated. RESULTS: Among the 117 patients with anti-LGI1 encephalitis, 69.2% (81/117) were male and 30.8% (36/117) were female. The median age of all patients at the onset of the disease was 57 years (interquartile range [IQR], 52-67). The median time from symptom onset to diagnosis was 8.7 weeks (IQR, 4.2-25). The main clinical features identified were seizures, cognitive impairment, and mental and behavioral abnormalities. Of the 117 patients, 109 were treated with immunotherapy. Symptoms including memory, mental ability, and behavior improved in all 109 patients after 3-5 days of treatment. The median time of follow-up for the treated patients was 33 months (IQR, 17-42). Of the treated patients, 16.2% (19/117) experienced a relapse, with a median delay of 5 months (IQR, 2.1-17) between onset and the first relapse. There were no mortalities over the follow-up period. CONCLUSION: The long-term outcome of patients with anti-LGI1 encephalitis was mostly favorable, although some patients continued to experience cognitive dysfunction. Early recognition is important for prompt initiation of immunotherapy that can improve clinical symptoms of anti-LGI1 encephalitis.

MiR224-5p Inhibitor Restrains Neuronal Apoptosis by Targeting NR4A1 in the Oxygen-Glucose Deprivation (OGD) Model.

This study was designed to investigate the molecular mechanism of stroke and to explore the effect of miR-224-5p in hypoxic cortical neurons. Firstly, we established a middle cerebral artery occlusion (MCAO) model with Sprague-Dawley rats. Triphenyltetrazolium chloride (TTC) staining showed the brain infarction of an MCAO rat. Longa scores of rats were significantly increased in 12th, 24th, and 48th hours after MCAO. Then, we found that miR-224-5p was increased after MCAO in rats by qRT-PCR. In order to investigate the effect of miR-224-5p in hypoxic neurons, we established an oxygen-glucose deprivation (OGD) model with cortical neurons. MiR-224-5p was also upregulated in neurons after OGD by qRT-PCR. After transfection of the miR-224-5p inhibitor, the number of neurons in the anti-miR-224-5p group significantly increased (P < 0.01) in comparison to the anti-NC group. Furthermore, Tuj1+ (neuronal marker) staining and TUNEL assay (to detect apoptotic cells) were performed in neurons. The survival of neurons in the anti-miR-224-5p group was significantly improved (P < 0.01), while the apoptosis of neurons in the anti-miR-224-5p group was significantly decreased (P < 0.01), when compared with that of the anti-NC group. In addition, we predicted that potential target genes of miR-224-5p were nuclear receptor subfamily 4 group A member 1 (NR4A1), interleukin 1 receptor antagonist (IL1RN), and ring finger protein 38 (RNF38) with bioinformatics databases, such as TargetScan, miRDB, miRmap, and miRanda. The result of qRT-PCR confirmed that NR4A1 was significantly decreased after hypoxic injury (P < 0.01). Meanwhile, luciferase reporter's assay indicated that NR4A1 was the direct target of miR-224-5p. Compared with the anti-miR-224-5p + siNC group, the number of cortical neurons and the length of the neuron axon in the anti-miR-224-5p + si-NR4A1 group were significantly decreased (P < 0.01), and the number of neuronal apoptosis in the anti-miR-224-5p + si-NR4A1 group was increased (P < 0.01). In conclusion, miR-224-5p played a crucial role in hypoxic neuron injury through NR4A1, which might be an important regulatory mechanism in OGD injury of neurons.

Antimyoclonic Effect of Levetiracetam and Clonazepam Combined Treatment on Myoclonic Epilepsy with Ragged-Red Fiber Syndrome with m.8344A>G Mutation.

BACKGROUND: Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers (MERRFs) has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects of monotherapies, including levetiracetam (LEV), clonazepam (CZP), valproic acid (VPA), and topiramate (TPM) compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures. METHODS: Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1-4 months of follow-up (mean: 82.9 ± 28.1 days), 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The follow-up period was 4-144 months (mean: 66.3 ± 45.3 months), the effective rates of monotherapy group (17 patients) and combination therapy group (12 patients) were analyzed by Chi-square test. RESULTS: The m.8344 A>G mutation was detected in all patients. There were four patients with partial response (4/17, two in the CZP group and two in the LEV group), ten patients with stable disease (10/17, six in the CZP group, three in the LEV group, and one in the TPM group), and three patients with progressive disease (3/18, two in the VPA group and one in the TPM group). Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance (12/12), eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy group in the efficacy of antimyoclonic seizures (χ2 = 13.7, P < 0.001). CONCLUSIONS: LEV in combination with CZP is an efficient and safe treatment for myoclonic seizures in patients with this disease exhibiting the m.8344A>G mutation.