Risk of COVID-19 infection and seizure exacerbation among patients with epilepsy during the peak of Omicron wave.

OBJECTIVES: Existing data regarding the risk of COVID-19 infection and its effects on seizure control in patients with epilepsy (PWE) are inconclusive. Our research aims to investigate the PWE who are susceptible to COVID-19 and what factors contribute to seizure exacerbation. METHODS: From Dec 28, 2022 to Feb 19, 2023, a cross-sectional questionnaire survey among adult PWE was conducted. The demographics, epilepsy-related information, COVID-19-related variables, and seizure outcomes after COVID-19 infection were collected. Multivariate logistic analyses were performed to determine the risk factors associated with COVID-19 infection and exacerbated seizures. RESULTS: Of 1557 PWE, 829 (53.2%) were infected with COVID-19 and 136 (16.4%) developed seizure exacerbation after COVID-19 infection. Overweight/obesity (OR 1.372, 95% CI 1.075-1.753, p = 0.011), immunocompromised (OR 3.301, 95% CI 1.093-9.974, p = 0.031), active epilepsy (OR 1.700, 95% CI 1.378-2.097, p < 0.001), and antiseizure medication (ASM) polytherapy (OR 1.314, 95% CI 1.065-1.621, p = 0.011) were associated with COVID-19 infection. Active epilepsy (OR 4.696, 95% CI 2.568-8.586, p < 0.001) and fever-associated seizures (OR 4.298, 95%CI 2.659-6.946, p < 0.001) were associated with seizure exacerbation. SIGNIFICANCE: PWE with overweight/obesity, immunocompromised, active epilepsy, and ASM polytherapy were at higher risk of COVID-19 infection. Once infected with COVID-19, seizures were exacerbated in PWE with active epilepsy and fever-associated seizures. PLAIN LANGUAGE SUMMARY: Patients with epilepsy (PWE) do not appear to be more susceptible to COVID-19 infection than general population. Once infected with COVID-19, 16.4% of PWE had seizure exacerbation. The PWE who have experienced seizures within the past 12 months before infection tend to contract COVID-19 more often, and are more likely to experience seizure exacerbations following COVID-19 infection.

Tongue Biting Event in Patients with Sleep-Related Facial Mandibular Myoclonus: A Case Series Study.

Background: Sleep-related facial mandibular myoclonus (SRFMM) remains rare in clinical practice. The aim of this study was to provide a comprehensive understanding of the electroclinical manner, therapeutic regimen, and prognosis of SRFMM. Methods: Twenty-three patients who were diagnosed with SRFMM by clinical manifestation, video-electroencephalography (EEG) and electromyography over bilateral masseter and temporalis muscles were enrolled. Clinical and electrophysiological evaluation as well as follow-up information were recorded and analyzed. Results: The cohort involved 4 infants and 19 adults with a mean onset age of 43.5 years for SRFMM, among whom 19 were male. Twenty-one patients complained of tongue injuries and disturbed night-time sleep. SRFMM in 4 patients were ascribed to oral aripiprazole, brainstem ischemia and brain trauma. In 62 SRFMM episodes, 93.5% occurred in NREM sleep and 6.5% in REM sleep, and all events were associated with EEG arousals. In 13 patients with or without clonazepam, the motor events gradually disappeared, and the rest turned to be sporadic. Conclusion: SRFMM is a characteristic parasomnia manifested by tongue biting and accompanying facial mandibular myoclonus, leading to disrupted sleep. Besides adults, infants can also experience SRFMM with spontaneous remission. Most patients respond well to clonazepam, eventually with favorable prognosis.

Sudden unexpected death in epilepsy disclosure causes anxiety in patients with epilepsy: a Chinese questionnaire survey.

Background and objective: Sudden unexpected death in epilepsy (SUDEP) has been regarded as a leading cause of premature death in patients with epilepsy (PWE). Although patients, relatives and caregivers have the right to be informed of SUDEP, neurologists prefer not to release the facts for fear of associated anxiety. In the study, a Chinese questionnaire survey was carried out to elucidate effect of SUDEP disclosure on anxiety in PWE and variables determining the anxiety of patients and provided suggestions for SUDEP disclosure. Methods: A survey study in China was conducted. We recruited 305 PWE from 3 tertiary epilepsy centers who attended outpatient clinic from December 2021 to February 2022. Two hundred and thirty-two PWE completed the screening evaluation, survey and Hamilton anxiety rating scale (HAMA) twice with 171 PWE completing third HAMA at follow-up. HAMA scores at baseline, T1, T2 were compared using analysis of variance and dependent samples t-test. The variables related to anxiety were screened out by univariate analysis and used for multivariate logistic regression. Result: We found 127 (54.7%) among the 232 participants experienced anxiety after SUDEP disclosure. HAMA scores at T1 were significantly higher than at baseline and T2, while there was no statistical difference between baseline and T2. Medical insurance, seizure severity, and whether the PWE supported SUDEP being disclosed to their relatives and caregivers only were associated with the occurrence of anxiety. Conclusion: SUDEP disclosures may cause short-term acute anxiety, but have no long-term effects in PWE. Acute anxiety caused by SUDEP disclosure may be more common in PWE with NCMI and severe seizures. Meanwhile, compared with indirect SUDEP disclosure to their relatives and caregivers, direct SUDEP disclosure to PWE reduces the risk of anxiety. Recommendations are provided to avoid anxiety caused by SUDEP disclosure.

Electroclinical Features of Sleep-Related Head Jerk.

STUDY OBJECTIVES: To evaluate clinical and electrophysiological features of sleep-related head jerk (SRHJ) and electromyographic activity of superficial neck muscles during head jerk. METHODS: Totally, 850 cases with video-polysomnography recording were collected, among which 50 presented with SRHJ. In these 50 patients, 15 underwent electromyography (EMG) check on bilateral sternocleidomastoid (SCM) and trapezius muscles as well as chin, while 35 had only chin EMG check. Further, the sensitivity and specificity of the both EMGs were calculated and compared. RESULTS: Six among the 50 SRHJ patients had a primary complaint of involuntary head jerks associated with impaired sleep. Approximately 76.1% of head jerks occurred during REM sleep with the median head jerk index of 5.9/h, 64.5% of which were associated with electroencephalogram arousals and 66.4% with body movements. One patient showed SRHJ predominantly in NREM sleep but also in wakefulness. Surface EMG of SCM/trapezius muscles showed a sensitivity of 92% and a specificity of 97.8%, whereas chin EMG had a sensitivity of 14.5% and a specificity of 98.8%. CONCLUSION: SRHJ was associated with electroencephalogram arousals and might interfere with sleep. Surface EMG of SCM/trapezius muscles exhibited a good accuracy in the revelation of SRHJ.

Protopanaxadiol ginsenoside Rd protects against NMDA receptor-mediated excitotoxicity by attenuating calcineurin-regulated DAPK1 activity.

Neuroprotective strategies in the treatment of stroke have been attracting a great deal of attentions. Our previous clinical and basic studies have demonstrated that protopanaxadiol ginsenoside-Rd (Rd), a monomer compound extracted from Panax ginseng or Panax notoginseng, has neuroprotective effects against ischemic stroke, probably due to its ability to block Ca2+ overload, an usual consequence of the overactivation of NMDA receptor (NMDAR). As an extending study, we explored here whether Rd exerted its neuroprotection as a novel NMDAR blocker. Our whole-cell patch-clamp results showed that Rd reduced NMDAR currents of cultured rat cortical neurons (EC50 = 7.7 µM) dose-dependently by acting on extrasynaptic NMDAR NR2b subunit. However, unexpectedly, cell transfection and radioligand binding assays revealed that Rd did not bind to the NMDAR channel directly. Alternatively, it inhibited the phosphorylation of NR2b at Ser-1303, a target of death associated protein kinase 1 (DAPK1). Moreover, cell-based and cell-free enzymatic assays showed that Rd did not inhibit the activity of DAPK1 directly, but blocked the activity of calcineurin, a key phosphatase for activating DAPK1. Importantly, other protopanaxadiol ginsenosides were also found to have potential inhibitory effects on calcineurin activity. Furthermore, as expected, calcineurin inhibition by cyclosporin A could mimic Rd's effects and protect against NMDA-, oxygen glucose deprivation- or transient ischemic stroke-induced neuronal injury. Therefore, our present study provided the first evidence that Rd could exert an inhibitive effect on NMDAR-triggered currents and sequential excitotoxicity through mitigation of DAPK1-mediated NR2b phosphorylation by attenuating calcineurin activity.

Ginsenoside Rd attenuates blood-brain barrier damage by suppressing proteasome-mediated signaling after transient forebrain ischemia.

Ischemic stroke damages the blood-brain barrier (BBB), which leads to brain edema and increases the risk of intracranial hemorrhage. Proteasome inhibition has been found to protect the BBB against cerebral ischemia by suppressing neuroinflammation-mediated matrix metalloproteases-9 (MMP-9) activation. We recently showed that ginsenoside Rd (Rd), a major active ingredient of Panax ginseng, could suppress proteasome-mediated inflammation and be efficient for treating ischemic stroke but downstream mechanisms were still unidentified. For this purpose, Sprague-Dawley rats were subjected to focal cerebral ischemic injury. The activity of proteasome and its downstream effectors nuclear factor-kappa B (NF-κB) and MMP-9 were evaluated. Rd reduced the activity of 20S proteasome in a cell-free assay and inhibited proteasome activity in brain lysates after ischemic stroke. Rd administration suppressed ischemic injury-induced NF-κB activity and IκB degradation mediated by the proteasome. Moreover, Rd reduced the activity and level of MMP-9, a downstream effector of NF-κB, and protected against BBB damage as evidenced by reduced Evan's Blue leakage and brain edema after cerebral ischemic injury. Jointly, these data demonstrate that ginsenoside Rd attenuates the pathogenesis of cerebral ischemia-induced BBB damage, probably by inhibiting proteasome activity and sequentially suppressing NF-κB/MMP-9 pathway.

Ginsenoside Rd promotes non-amyloidogenic pathway of amyloid precursor protein processing by regulating phosphorylation of estrogen receptor alpha.

AIMS: Previous study demonstrated that Ginsenoside Rd. (GS-Rd) could improve cognitive and memory function in animal model of Alzheimer's disease. This study was aimed to investigate whether GS-Rd could improve non-amyloidogenic pathway by activating estrogen receptor (ER). MAIN METHODS: 10mg/kg GS-Rd in ovariectomy (OVX)+GS-Rd group and equivalent volume of saline in sham operated group and OVX group were administrated intraperitoneally for two months, respectively. The Morris Water Maze was used to examine cognitive function of rats, with sAPPα and Aß levels in the hippocampi measured. The culture medium of HT22 hippocampal neuronal cells were incubated with GS-Rd, ER antagonist ICI182.780, MAPK inhibitor PD98059, or PI3Kinhibitor LY294002, respectively. sAPPα levels was measured, and expression of α-secretase, sAPPα, ß-secretase, Aß, phosphorylation form of AKT (p-AKT), total AKT, p-ERK, total ERK, p-ERα, total ERα, p-ERß and total ERß were examined by Western blot to explore the estrogenic-like activity of GS-Rd. KEY FINDINGS: GS-Rd attenuate cognitive and memory impairment, increased levels of sAPPα and reduced extracellular Aß of OVX rats. In HT22, GS-Rd could upregulate sAPPα level, which can be inhibited by inhibitor of MAPK and PI3K pathway. In addition, inhibitor of estrogen receptor prevented GS-Rd triggered release of sAPPα and activation of MAPK and PI3K pathways. GS-Rd could increase expression of α-secretase and sAPPα, while decrease expression of ß-secretase and Aß. Besides, GS-Rd promoted phosphorylation of estrogen receptor alpha at Ser118 residue. SIGNIFICANCE: Our findings show that GS-Rd enhances learning and memory function of OVX rats by activating estrogen-like activity.

Human B cells have an active phagocytic capability and undergo immune activation upon phagocytosis of Mycobacterium tuberculosis.

The paradigm that B cells are nonphagocytic was taken for granted for a long time until phagocytic B cells were found in early vertebrate animals. Thereafter, limited evidence has shown that human B cells may also internalize bacteria. However, whether human B cells can actively phagocytose bacteria has been less extensively investigated; in particular, the mechanisms and significance of the phagocytosis require clarification. Here, we show that the human Raji B cell line can phagocytose both live and dead Mycobacterium tuberculosis (Mtb), and the phagocytosed Mtb in turn affects the immune functions of the B cells. After incubation of Raji cells with Mtb, our confocal microscopy, electron microscopy and flow cytometry data showed that Raji cells effectively engulfed Mtb as well as latex beads. The phagocytic rate was proportional to the incubation time and the amount of Mtb or beads added. Additionally, we found that normal human serum could enhance the ability of Raji cells to phagocytose Mtb, while heat-inactivated serum reversed this promoting effect. The phagocytic process of B cells could partially be inhibited by cytochalasin B, an actin inhibitor. Importantly, the phagocytosed Mtb could regulate B cell immune functions, such as stimulating IgM production and upregulating the expression of the antigen-presenting costimulatory molecules CD80 and CD86. Therefore, our results provide the first evidence that human B cells can phagocytose Mtb in an active manner that is independent of bacterial viability, and phagocytosed Mtb can in turn regulate the immune activation of B cells.

Ginsenoside Rd attenuates Aß25-35-induced oxidative stress and apoptosis in primary cultured hippocampal neurons.

One of the most common pathological changes in Alzheimer's disease (AD) brain is the large number of amyloid ß (Aß) peptides accumulating in lesion areas. Ginsenosides are the most active components extracted from ginseng. Ginsenoside Rd (GRd) is a newly discovered saponin that has a stronger pharmacological activity than other ginsenosides, especially in neuroprotection. Here we examined the neuroprotective effects of GRd against neuronal insults induced by Aß25-35 in primary cultured hippocampal neurons. A 10µM GRd treatment significantly prevented the loss of hippocampal neurons induced by Aß25-35. In addition, GRd significantly ameliorated Aß25-35-induced oxidative stress by decreasing the reactive oxygen species (ROS) production and malondialdehyde (MDA) level, and increasing the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px); which is similar in treatments with 10µM of probucol (PB) and 100µM of edaravone (EDA). Moreover, our present study demonstrated that GRd significantly enhanced the expression of Bcl-2 mRNA, and decreased the expressions of Bax mRNA and Cyt c mRNA. GRd also downregulated the protein level of cleaved Caspase-3 compared to controls. These results highlighted the neuroprotective effects of GRd against Aß25-35-induced oxidative stress and neuronal apoptosis, suggesting that this may be a promising therapeutics against AD.

Ginsenoside Rd blocks AIF mitochondrio-nuclear translocation and NF-κB nuclear accumulation by inhibiting poly(ADP-ribose) polymerase-1 after focal cerebral ischemia in rats.

Our previous clinical and basic studies have demonstrated that ginsenoside Rd (GS-Rd) has remarkable neuroprotective effects after cerebral ischemia but the underlying mechanisms are still unknown. In our latest studies, we revealed that GS-Rd could prevent mitochondrial release of apoptosis-inducing factor (AIF) and reduce inflammatory response following transient focal ischemia in rats. Poly(ADP-ribose) polymerase-1 (PARP-1) is required for both AIF release from mitochondria and NF-κB-mediated inflammation. Here, we investigated whether GS-Rd could act on PARP-1 and subsequently affect AIF translocation and NF-κB activation. Sprague-Dawley rats were treated with GS-Rd (10 mg/kg) 30 min before surgery with the right middle cerebral artery occlusion, and at different time points following cerebral ischemia, brain tissues were collected for western blotting analysis. Our results showed that GS-Rd significantly attenuated ischemia-triggered increased levels of Poly(ADP-ribose), an enzymatic product catalyzed by PARP-1, but not altered the expression of PARP-1 per se. Meanwhile, GS-Rd pretreatment reduced AIF mitochondrio-nuclear translocation and inhibited NF-κB p65 subunit nuclear accumulation after cerebral ischemia. Therefore, our findings provide the first evidence that GS-Rd can inhibit PARP-1 activity and sequential AIF translocation and NF-κB nuclear accumulation, which may be responsible for GS-Rd's neuroprotection against both neuronal cell death and inflammation after ischemic stroke.