Inhibition of NLRP3 inflammasome alleviates cognitive deficits in a mouse model of anti-NMDAR encephalitis induced by active immunization.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neurological disorder, characterized by cognitive deficits as one of its vital features. The nucleotide-binding oligomerization domain-like receptor (NLRP3) inflammasome is a key contributor to neuroinflammation and cognitive deficits in neurological diseases. However, the underlying mechanism of anti-NMDAR encephalitis remains unclear, and the biological function of the NLRP3 inflammasome in this condition has not been elucidated. In this study, a mouse model of anti-NMDAR encephalitis was induced by active immunization with the GluN1356-385 peptide (NEA model). The NLRP3 inflammasome in the hippocampus and temporal cortex was investigated using real-time quantitative PCR (RT-qPCR), western blotting, and immunofluorescence staining. The impact of MCC950 on cognitive function and NLRP3 inflammation was assessed. Confocal immunofluorescence staining and Sholl analysis were employed to examine the function and morphology of microglia. In the current study, we discovered overactivation of the NLRP3 inflammasome and an enhanced inflammatory response in the NEA model, particularly in the hippocampus and temporal cortex. Furthermore, significant cognitive dysfunction was observed in the NEA model. While, MCC950, a selective inhibitor of the NLRP3 inflammasome, sharply attenuated the inflammatory response in mice, leading to mitigated cognitive deficits of mice and more regular arrangements of neurons and reduced number of hyperchromatic cells were also observed in the hippocampus area. In addition, we found that the excess elevation of NLRP3 inflammasome was mainly expressed in microglia accompanied with the overactivation of microglia, while MCC950 treatment significantly inhibited the increased number and activated morphological changes of microglia in the NEA model. Altogether, our study reveals the vital role of overactivated NLRP3 signaling pathway in aggravating the inflammatory response and cognitive deficits and the potential protective effect of MCC950 in anti-NMDAR encephalitis. Thus, MCC950 represents a promising strategy for anti-inflammation in anti-NMDAR encephalitis and our study lays a theoretical foundation for it to become a clinically targeted drug.

The miR-23b-3p from adipose-derived stem cell exosomes alleviate inflammation in mice experiencing kainic acid-induced epileptic seizures.

Epilepsy is a common neurologic disorder. While a good clinical solution is still missing, studies have confirmed that exosomes (Exos) derived from adipose-derived stem cells (ADSCs) had a therapeutic effect on various diseases, including neurological diseases. Therefore, this study aimed to reveal whether ADSC-Exo treatment could improve kainic acid (KA)-induced seizures in epileptic mice. ADSCs and Exos were isolated. Mice were generated with KA-induced epileptic seizures. ELISA was used to detect inflammatory factor expression. Luciferase reporter analysis detection showed a relationship among miR-23b-3p, STAT1, and glyoxylate reductase 1 (GlyR1). ADSC-Exos had a protective effect on KA-induced seizures by inhibiting inflammatory factor expression and the M1 microglia phenotype. The result showed that miR-23b-3p played an important role in the Exo-mediated protective effect in KA-induced seizures in epileptic mice by regulating STAT1 and GlyR1. Luciferase reporter analysis confirmed that miR-23b-3p interacted with the 3'-UTR of STAT1 and GlyR1. The miR-23b-3p inhibited M1 microglia-mediated inflammatory factor expression in microglial cells by regulating STAT1 and GlyR1. The downregulation of miR-23b-3p decreased the protective effect of ADSC-Exos on KA-induced seizures in epileptic mice. The miR-23b-3p from ADSC-Exos alleviated inflammation in mice with KA-induced epileptic seizures.

Rapamycin alleviates mitochondrial dysfunction in anti-NMDAR encephalitis mice.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent forms of autoimmune encephalitis, characterized by a series of neurological and psychiatric symptoms, including cognitive impairment, seizures and psychosis. The underlying mechanism of anti-NMDAR encephalitis remains unclear. In the current study, the mouse model of anti-NMDAR encephalitis with active immunization was performed. We first uncovered excessive mitochondrial fission in the hippocampus and temporal cortex of anti-NMDAR encephalitis mice, indicated by elevated level of Phospho-DRP1 (Ser616) (p-Drp1-S616). Moreover, blockade of the autophagic flux was also demonstrated, leading to the accumulation of fragmented mitochondria, and elevated levels of mitochondrial reactive oxygen species (mtROS) and mitochondrial DNA (mtDNA) in anti-NMDAR encephalitis. More importantly, we found that the mTOR signaling pathway was overactivated, which could aggravate mitochondrial fission and inhibit autophagy, resulting in mitochondrial dysfunction. While rapamycin, the specific inhibitor of the mTOR signaling pathway, significantly alleviated mitochondrial dysfunction by inhibiting mitochondrial fission and enhancing autophagy. Levels of mtROS and mtDNA were markedly reduced after the treatment of rapamycin. In addition, rapamycin also significantly alleviated cognitive dysfunction and anxious behaviors found in anti-NMDAR encephalitis mice. Thus, our study reveals the vital role of mitochondrial dysfunction in pathological mechanism of anti-NMDAR encephalitis and lays a theoretical foundation for rapamycin to become a clinically targeted drug for anti-NMDAR encephalitis.

Dual hypoxia-responsive supramolecular complex for cancer target therapy.

The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach.

Elevated cerebrospinal fluid YKL-40 levels in patients with anti-gamma-aminobutyric- acid-B receptor encephalitis.

OBJECTIVE: Anti-gamma-aminobutyric-acid-B receptor (GABAbR) encephalitis is a rare form of autoimmune encephalitis. Until now, there are few biomarkers that can indicate the severity and prognosis of patients with anti-GABAbR encephalitis. The objective of this study was to exam the changes of chitinase-3-like protein 1 (YKL-40) in patients with anti-GABAbR encephalitis. In addition, whether YKL-40 could indicate the disease severity was also evaluated. METHODS: The clinical features of 14 patients with anti-GABAbR encephalitis and 21 patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis were retrospectively studied. YKL-40 levels in serum and cerebral fluid (CSF) of patients were detected by enzyme-linked immunosorbent assay. The correlation of modified Rankin Scale (mRS) score of encephalitis patients and YKL40 levels were analyzed. RESULTS: YKL-40 levels in CSF were significantly higher in patients with anti-GABAbR encephalitis or anti-NMDAR encephalitis than those in controls. YKL-40 levels between these two encephalitis groups were not different. Moreover, YKL-40 levels in CSF from patients with anti-GABAbR encephalitis were positively correlated with the mRS score at admission and at 6-month follow-up. CONCLUSION: YKL-40 level is elevated in CSF from patients with anti-GABAbR encephalitis at early disease stage. YKL-40 may be a potential biomarker indicating the prognosis of patients with anti-GABAbR encephalitis.

Clinical features of epileptic seizures in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.

BACKGROUND AND PURPOSE: This study aimed to characterize the clinical features of epilepsy in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and analyze the clinical determinants for drug-resistant epilepsy in MELAS. METHODS: A single-center, retrospective study was conducted to investigate the clinical features of epilepsy in patients with MELAS. Collected variables included seizure semiology, electroencephalography (EEG), muscle biopsy, genetic testing, neuroimaging findings, resting serum lactic value and modified Rankin scale (mRS) of patients with MELAS. We also investigated the differences between the adult-onset group and the child-onset group and analyzed the risk factors for drug-resistant epilepsy in MELAS. RESULTS: We studied 97 patients (56 males: 41 females) with confirmed MELAS. Epileptic seizure occurred in 100.0% of patients and the initial symptom of 69.1% patients was epileptic seizure. The average age of disease onset was 21.0 years, ranging from 2 to 60 years. The seizure types of these patients with MELAS were variable, with generalized onset (51.5%) to be the most common type. The EEG changes in the patients with MELAS were mainly slow wave (90.9%) and epileptiform discharge (68.2%). The child-onset group with earlier seizure onset presented significantly higher resting serum lactic value (p = 0.0048) and lower incidence of stroke-like lesion in the brain (p = 0.003), especially in the temporal lobe (p < 0.001), compared with the adult-onset group. Importantly, drug-resistant epilepsy in MELAS was demonstrated to be closely related to the earlier age of seizure onset (p = 0.013), as well as the higher mRS score (p < 0.001) and higher resting serum lactic value (p = 0.009). CONCLUSION: Early identification of MELAS should be considered among individuals with recurrent epilepsy through clinical screening. Age of seizure onset and resting serum lactic value may predict the development of drug-resistant epilepsy in MELAS. Close observation and appropriate anti-epileptic treatment are indispensable for individuals with MELAS to improve the prognosis. Further studies with larger sample size are required to further evaluate the risk factors of drug-resistant epilepsy in MELAS and provide guidance on treatment of MELAS.

Anti-γ-aminobutyric acid-A receptor encephalitis with refractory seizures and cognitive impairment in a young woman: A case report.

Anti-γ-aminobutyric acid-A receptor (GABAAR) encephalitis is an underappreciated cause of autoimmune encephalitis and remains refractory to antiepileptic therapies unless autoimmune responses are addressed. Herein, we reported a case of anti-GABAAR encephalitis in a young woman. A 29-year-old woman was admitted because of seizures for 10 months, memory decline for 7 months, and paroxysmal limbs jerking for 5 months. At admission, the patient showed mild cognitive impairment. Cell-based assays found no antibodies associated with common autoimmune encephalitis in the cerebrospinal fluid (CSF) and no antibodies in the plasma and CSF against central nervous system demyelination-associated proteins. MRI revealed multiple cortical-subcortical abnormalities and electroencephalography demonstrated periodic epileptiform discharges during paroxysmal clonus. A second test 1 month after admission detected antibodies against GABAAR α1/ß3/γ2 in the plasma and CSF, leading to a diagnosis of anti-GABAAR encephalitis. The patient received intravenous immunoglobulin, prednisone, azathioprine, and levetiracetam and recovered from limb jerks and was no longer amnesic. A second episode occurred after an apparent cold and was managed by intravenous immunoglobulin, cyclophosphamide, and methylprednisolone with subsequent prednisone and levetiracetam. The patient was able to speak and ambulate after 15 days of treatment. Her MMSE, MoCA, and MRS scores improved. Physicians should harbor a high index of suspicion of anti-GABAAR encephalitis in refractory encephalitis patients with the manifestation of seizures or psychiatric disorders. Tests for a comprehensive panel of antibodies associated with anti-GABAAR encephalitis should be carried out in suspected cases and immunotherapy should be promptly initiated upon diagnosis to prevent irreversible neurological damage.

Probe Synthesis Reveals Eukaryotic Translation Elongation Factor†1 Alpha†1 as the Anti-Pancreatic Cancer Target of BE-43547A2.

The natural product, BE-43547A2 , decreases pancreatic cancer cell stemness. However, its anticancer molecular mechanisms have not been fully established. Based on structure-activity relationships of BE-43547A2 , we synthesized a probe and investigated its potential targets using an in situ click reaction. We found that BE-43547A2 exerts its anticancer effects by covalently binding the cysteine234 (C234) residue of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1). This binding mode was confirmed by a series of experiments including a xenograft mouse model. We also determined that eEF1A1 plays an important role in regulating pancreatic cancer cell stemness. Analyses of 99 clinical pancreatic cancer samples revealed that eEF1A1 expressions are closely correlated with clinicopathological grade and patient survival. In conclusion, eEF1A1 is involved in pancreatic cancer progression and is therefore, a promising novel covalent target for pancreatic cancer treatment.

Total synthesis and stereochemical assignment of rakicidin F.

Total synthesis of rakicidin F was accomplished in 20 linear steps (0.68% overall yield), which enabled the configural determination of its six stereogenic centers as 2R, 15R, 16R, 17S, 19S, and 21S. The macrolactonization of the rakicidin linear precursor was investigated and the unsuccessful results might be attributed to the steric hindrance near C16-OH.

Risk factors for postictal generalized EEG suppression in generalized convulsive seizure: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Postictal generalized EEG suppression (PGES) has been suggested as a pathophysiological hallmark for sudden unexpected death in epilepsy (SUDEP). We aimed to characterize the clinical determinants for PGES occurrence after generalized convulsive seizures (GCS). METHODS: We systematically searched Pubmed, Embase and Medline databases up to 30 August 2021. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted by two independent reviewers. Studies reporting potential risk factors of PGES occurrence in GCS were included for subsequent meta-analysis and PGES was defined as a generalized EEG attenuation of any duration >1s below 10µV, immediately or within 30s after an ictal EEG pattern has terminated. A fixed-effects model was applied when the heterogeneity is low (I2 values < 50%). Otherwise, a random-effects model was used (I2 values ≥ 50%). We assessed the odds ratio (OR) as outcome measure for dichotomous variables and the STD Mean Difference (SMD) for continuous variables. The Begg test and the Egger test was applied in the assessment of publication bias. RESULTS: A total of 15 relevant studies were identified, enrolling 2057 GCSs. The incidence of PGES in GCS from 15 studies varied from 23% to 86%. The longer tonic phase duration (SMD, 0.26; 95%CI, 0.13 to 0.39; p < 0.001), sleep state at GCS onset (OR,1.63; 95%CI, 1.24 to 2.16; p = 0.001), older age of epilepsy onset (SMD, 0.48; 95%CI, 0.21 to 0.75; p = 0.001), the presence of postictal immobility (OR, 78.05; 95%CI, 32.31 to 188.53; p < 0.001) and oxygen desaturation nadir (SMD, -0.54; 95%CI, -0.76 to -0.33; p < 0.001) showed significant association with the likelihood of having PGES in GCS, but not total seizure duration (SMD, -0.06; 95%CI, -0.20 to 0.08; p = 0.385), tonic-clonic duration (SMD, -0.12; 95%CI, -0.26 to 0.01; p = 0.071), clonic phase duration (SMD, -0.09; 95%CI, -0.27 to 0.08; p = 0.293), epilepsy duration of patients (SMD, -0.09; 95%CI, -0.27 to 0.08; p = 0.293) or lack of early O2 administration (OR, 1.59; 95%CI, 0.80 to 3.17; p = 0.184). CONCLUSION: The current study informed that PGES is common after GCS. Early identification should be considered among individuals with GCS at high risk of PGES through clinical screening. Further studies with larger sample size are required for individualized evaluation of the risk of PGES in GCS and more effort is needed to further evaluate the risk of SUDEP.

MRI Characteristics of Autoimmune Encephalitis With Autoantibodies to GABAA Receptor: A Case Series.

BACKGROUND AND OBJECTIVES: To characterize the clinical and neuroimaging phenotypes of patients with autoantibodies to γ-aminobutyric acid type A receptor (GABAAR). METHODS: Ten patients with autoantibodies against GABAAR from Huashan Hospital Autoimmune Encephalitis cohort were identified. We used MRI assessments and clinical examinations to summarize major clinical profile and visualize and quantify lesion distribution features. The relationship between clinical features, neuroimaging phenotypes, and topology of GABAAR expression were further investigated. RESULTS: The median age at onset of 10 patients (8 male patients and 2 female patients) with anti-GABAAR encephalitis was 41.5 years (range: 17-73 years). All patients had prominent seizures and multifocal spotted or confluent lesions involved in limbic, frontal, and temporal lobes on brain MRI. Bilateral but asymmetric lesions in cingulate gyri were observed in all patients. These involved lesions could change dynamically with immunotherapies and relapse. Distribution of patients' brain MRI lesions was positively correlated with gene expression level of ß3 subunit-containing GABAAR (Spearman ρ = 0.864, p = 0.001), the main target of autoantibodies. According to topology of lesions, patients with anti-GABAAR encephalitis could be classified into 2 clinical-radiological types: confluent type with bilateral confluent lesions involved in almost all limbic, frontal, and temporal lobes and spotted type with multiple scattered small-to-medium patchy lesions. Patients with confluent type exhibited worse clinical presentations and outcomes when compared with those with spotted type (maximum modified Rankin scale [mRS]: 5 [5-5] vs 3.5 [3-4], respectively, p = 0.008; follow-up mRS: 4 [2-6] vs 0.5 [0-1], respectively, p = 0.016). DISCUSSION: Anti-GABAAR encephalitis has distinctive neuroimaging phenotype. Cingulate gyri were frequently involved in this disorder. The topology of lesions might be associated with the distribution of ß3 subunit-containing GABAAR and reflected patients' disease severity and outcomes.

Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and In Vivo Biological Evaluation for Acute Lung Injury.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a natural macrocyclic peptide reported to be a potent elastase inhibitor. Herein, we completed the first total synthesis of CTL-A in 24 linear steps. The key reactions include three-component MAC reactions and two late-stage oxidations. We also provided seven CTL-A analogues and elucidated preliminary structure-activity relationships. The in vivo ALI mouse model further suggested that CTL-A alleviated acute lung injury with reductions in lung edema and pathological deterioration, which is better than sivelestat, one approved elastase inhibitor. The activity of CTL-A against elastase, along with its cellular safety and well-established synthetic route, warrants further investigation of CTL-A as a candidate against COVID-19 pathogeneses.

The well responsiveness of drug-resistant focal seizures in anti-AMPA2 receptor encephalitis to perampanel treatment.

Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is an anti-neuronal surface antigen autoimmune encephalitis and is relatively rare. Our study evaluated a patient who developed anti-AMPA2 receptor encephalitis with memory deficits and refractory focal seizures as paroxysmal jerking on right face as well as dystonic seizure on right hand. On this patient, the combination treatment of levetiracetam, carbamazepine, and clonazepam, monthly periodic intravenous immunoglobin and immunosuppressive therapies for 5 months was not effective for the focal seizures, while his memory loss was slightly improved. However, adjunctive perampanel treatment led to a rapid relief of seizures. Perampanel is suggested in seizures associated with anti-AMPA receptor encephalitis by directly attenuating nerve hyperexcitability caused by glutamate and Ca2+-permeable GluA4 subunit of AMPA receptors.

CHI3L1 in the CSF is a potential biomarker for anti-leucine-rich glioma inactivated 1 encephalitis.

Objective: Anti-leucine-rich glioma inactivated 1(LGI1) encephalitis is one rare autoimmune encephalitis which is accompanied by inflammatory responses. (Anti-leucine-rich glioma inactivated 1 (anti-LGI1) encephalitis is an autoimmune disease mediated by inflammatory responses.)This study aimed to investigate the Chitinase 3-like 1(CHI3L1) in anti-LGI1encephalitis patients and evaluate its association with modified Rankin Scale (mRS) score in anti-LGI1 encephalitis at admission and 6 months follow-up.(This study looked into the relationship between Chitinase 3-like 1 (CHI3L1) and the modified Ranking Scale (mRS) score in anti-LGI1 encephalitis patients at admission and 6 months later.). Methods: Thirty-five patients with anti-LGI1 encephalitis and 22 patients with non-inflammatory neurological disease were enrolled in this study. (We enrolled 35 patients with anti-LGI1 encephalitis and 22 patients with non-inflammatory neurological disease.)Cerebrospinal fluid (CSF) and serum levels of CHI3L1 were measured by enzyme-linked immunosorbent assay. (We quantified CHI3L1 in the serum and cerebrospinal fluid (CSF) by performing an enzyme-linked immunosorbent assay.)Patients were evaluated for mRS score at admission and at 6 months follow-up.(We recorded the mRS score of the patients at admission and 6 months later.). Results: CHI3L1 levels in CSF and serum were highly elevated in patients with anti-LGI1 encephalitis at admission compared those with the controls.(At admission, patients with anti-LGI1 encephalitis had elevated CHI3L1 levels in the CSF and serum.) Additionally, patients presenting with cognitive impairment had significantly higher CSF CHI3L1 levels and mRS scores than those without cognitive impairment symptoms. Patients presenting with only faciobrachial dystonic seizures at admission had lower CSF CHI3L1 levels than those with other symptoms. Finally, CSF CHI3L1 levels were positively correlated with CSF lactate levels. Conclusion: CHI3L1 level in CSF is correlated with the severity and prognosis of anti-LGI1 encephalitis. (CSF CHI3L1 levels are correlated with the severity and prognosis of anti-LGI1 encephalitis.).

The Clinical Features of FLAIR-Hyperintense Lesions in Anti-MOG Antibody Associated Cerebral Cortical Encephalitis with Seizures: Case Reports and Literature Review.

Background: The presence of fluid attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated cerebral cortical encephalitis with seizures (FLAMCES) was recently reported. However, the clinical characteristics and outcome of this rare clinico-radiographic syndrome remain unclear. Methods: The present study reported two new cases. In addition, cases in the literature were systematically reviewed to investigate the clinical symptoms, magnetic resonance imaging (MRI) abnormalities, treatments and prognosis for this rare clinico-radiographic syndrome. Results: A total of 21 cases were identified during a literature review, with a mean patient age at onset of 26.8 years. The primary clinicopathological characteristics included seizures (100%), headache (71.4%), fever (52.3%) and other cortical symptoms associated with the encephalitis location (61.9%). The common seizure types were focal to bilateral tonic-clonic seizures (28.6%) and unknown-onset tonic-clonic seizures (38.1%). The cortical abnormalities on MRI FLAIR imaging were commonly located in the frontal (58.8%), parietal (70.6%) and temporal (64.7%) lobes. In addition, pleocytosis in the cerebrospinal fluid was reported in the majority of the patients (95.2%). All patients received a treatment regimen of corticosteroids and 9 patients received anti-epileptic drugs. Clinical improvement was achieved in all patients; however, one-third of the patients reported relapse following recovery from cortical encephalitis. Conclusions: FLAMCES is a rare phenotype of MOG-associated disease. Thus, the wider recognition of this rare syndrome may enable timely diagnosis and the development of suitable treatment regimens.

Automated Analysis of Risk Factors for Postictal Generalized EEG Suppression.

Rationale: Currently, there is some ambiguity over the role of postictal generalized electro-encephalographic suppression (PGES) as a biomarker in sudden unexpected death in epilepsy (SUDEP). Visual analysis of PGES, known to be subjective, may account for this. In this study, we set out to perform an analysis of PGES presence and duration using a validated signal processing tool, specifically to examine the association between PGES and seizure features previously reported to be associated with visually analyzed PGES. Methods: This is a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of SUDEP in adult patients with intractable epilepsy. We studied videoelectroencephalogram (vEEG) recordings of generalized convulsive seizures (GCS) in a cohort of patients in whom respiratory and vEEG recording were carried out during the evaluation in the epilepsy monitoring unit. A validated automated EEG suppression detection tool was used to determine presence and duration of PGES. Results: We studied 148 GCS in 87 patients. PGES occurred in 106/148 (71.6%) seizures in 70/87 (80.5%) of patients. PGES mean duration was 38.7 ± 23.7 (37; 1-169) seconds. Presence of tonic phase during GCS, including decerebration, decortication and hemi-decerebration, were 8.29 (CI 2.6-26.39, p = 0.0003), 7.17 (CI 1.29-39.76, p = 0.02), and 4.77 (CI 1.25-18.20, p = 0.02) times more likely to have PGES, respectively. In addition, presence of decerebration (p = 0.004) and decortication (p = 0.02), older age (p = 0.009), and hypoxemia duration (p = 0.03) were associated with longer PGES durations. Conclusions: In this study, we confirmed observations made with visual analysis, that presence of tonic phase during GCS, longer hypoxemia, and older age are reliably associated with PGES. We found that of the different types of tonic phase posturing, decerebration has the strongest association with PGES, followed by decortication, followed by hemi-decerebration. This suggests that these factors are likely indicative of seizure severity and may or may not be associated with SUDEP. An automated signal processing tool enables objective metrics, and may resolve apparent ambiguities in the role of PGES in SUDEP and seizure severity studies.

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China.

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.