Anti-seizure medications (ASMs) are the most important and basic treatment for epilepsy, and are also the first choice for epilepsy treatment, but about one-third of patients have drug resistance. Perampanel (PER), as a novel third generation ASMs, inhibits the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) through non-competitive inhibition. AMPA plays an anti-seizure role. Since its approval in China in 2021, it has been mainly used in the treatment of focal epilepsy (with or without general seizure) as a single drug or addition, and has good safety, effectiveness and tolerability. Self-limited epilepsy with centrotemporal spikes (SeLECTS) is a common childhood focal epilepsy syndrome, accounting for 15% ~ 25% of various childhood epilepsies, PER has important advantages in clinical studies and has shown certain curative effect. At the same time, the overall effect of PER on cognition was neutral, with no systemic cognitive deterioration or improvement. In view of the relatively short application time of PER, which is still a new drug, this article will review the mechanism of action, dose, add-on (single drug) treatment, adverse events and, in order to provide clinicians with more drug choices and facilitate the individualized diagnosis and treatment of epilepsy.
Objective To identify clinical and electroencephalographic features of the variants of benign childhood epilespy with centrotemporal spikes (BECTs). Methods A total of 51 children with BECTs were restrospectively reviewed from July 2008 to December 2015 in the study, including the clinical data, electrophysiologic characteristics and effects of antiepileptic drugs. Results Age of the patients ranged from 2.5 to 11 years old, which were averged 7.03 years old. The duration of disease varied from 4 days to 6 years, and 2.36 years in average. Nearly continuous electric discharge were detected in slow sleeping, during which, the busting index was 90% in 19 patients’, 78% in 26, 52% in 6. the average busting index was 82.44%.47 patients (92.1%) had synptom of hand shaking; 8 patients(15.6%) had oropharyngeal automatism; 7 patients (13.7%) had language barrier; sample absence seizures or tumble occurred in 11 patients (21.5%); cognitive declined in 17 patients (33.3%). VPA monotherapy had good effect on 12 patients, 33 patients need combination of VPA and CBZ. However, there’s still 6 patients need adrenocortical hormone to control seizures. Conclusion The variants of BECT are companied with obvious deterioration of EEG. Lack of standard AED therapy may cause aggravations, so we need to monitor EEG closely. We use AED not merely in orde to control seizure but also inhibit abnormal EEG discharge.
The rapid development of artificial intelligence put forward higher requirements for the computational speed, resource consumption and the biological interpretation of computational neuroscience. Spiking neuron networks can carry a large amount of information, and realize the imitation of brain information processing. However, its hardware is an important way to realize its powerful computing ability, and it is also a challenging technical problem. The memristor currently is the electronic devices that functions closest to the neuron synapse, and able to respond to spike voltage in a highly similar spike timing dependent plasticity (STDP) mechanism with a biological brain, and has become a research hotspot to construct spiking neuron networks hardware circuit in recent years. Through consulting the relevant literature at home and abroad, this paper has made a thorough understanding and introduction to the research work of the spiking neuron networks based on the memristor in recent years.
Objective The ReHo, ALFF, fALFF of resting-state functional magnetic resonance imaging (RS-fMRI) technology were used to study the influencing factors and neural mechanism of cognitive dysfunction in patients with benign epilepsy of childhood with centrotemporal spikes (BECT). Methods Fourteen patients were enrolled (from April 2015 to March 2018) from epilepsy specialist outpatients and Functional Department of Neurosurgery of Tianjin Medical University General Hospital. They underwent the long term VEEG monitoring (one sleep cycle was included at least), the Wechsler Intelligence Scale (China Revised), the head MRI and RS-fMRI examinations. Spike-wave index (SWI), FIQ, VIQ, PIQ scores were calculated. According to full-scale IQ (FIQ), they were divided into two groups: FIQ<90 (scores range from 70 to 89, the average score was 78.3±8.9, 6 cases) and FIQ≥90 (scores range from 90 to 126, the average score was 116.6±12.9, 8 cases). SPSS21.0 statistical software was used to compare the general clinical data and SWI of the two groups, and the correlation between clinical factors and the evaluation results of Wechsler Intelligence Scale was analyzed. The RS-fMRI images were preprocessed and the further data were analysed by two independent samplest-test under the whole brain of regional homogeneity (ReHo), amplitude of low frequency fluctuation (ALFF) and fractional of ALFF (fALFF) methods. The differences of brain activation regions in RS-fMRI between the two groups were observed, and the results of general clinical data, SWI and cognitive function test were compared and analyzed comprehensively. Results The differences of SWI were statistically significant (P<0.05): FIQ<90 group were greater than FIQ≥90 group. The FIQ, VIQ and PIQ of two groups were negatively correlated with SWI (P<0.05). And the FIQ and PIQ were negatively correlated with the total number of seizures (P<0.05). Compared with FIQ≥90 group by two samplet-test based on whole level ReHo, ALFF, fALFF methods, deactivation of brain regions of FIQ<90 group include bilateral precuneus, posterior cingulate and occipital lobe, and enhanced activation of brain regions include left prefrontal cortex, bilateral superior frontal gyrus medial and right precentral gyrus, supplementary motor area, angular gyrus, supramarginal gyrus, middle temporal gyrus, bilateral insular lobe and subcortical gray matter structures. Conclusions Frequent epileptic discharges during slow wave sleep and recurrent clinical episodes were risk factors for cognitive impairment in BECT patients. Repeated clinical seizures and frequent subclinical discharges could cause dysfunction of local brain areas associated with cognition and the default network, resulting in patients with impaired cognitive function.
A novel coronavirus (SARS-CoV-2) that broke out at the end of 2019 is a newly discovered highly pathogenic human coronavirus and has some similarities with severe acute respiratory syndrome coronavirus (SARS-CoV). Angiotensin-converting enzyme 2 (ACE2) is the receptor for infected cells by SARS-CoV. SARS-CoV can invade cells by binding to ACE2 through the spike protein and SARS-CoV-2 may also infect cells through ACE2. Meanwhile, ACE2 also plays an important role in the course of pneumonia. Therefore the possible role of ACE2 in SARS and coronavirus disease 2019 (COVID-19) is worth discussing. This paper briefly summarized the role of ACE2 in SARS, and discussed the possible function of ACE2 in COVID-19 and potential risk of infection with other organs. At last, the function of ACE2 was explored for possible treatment strategies for SARS. It is hoped to provide ideas and theoretical support for clinical treatment of COVID-19.
Transcranial magneto-acoustical stimulation (TMAS), utilizing focused ultrasound and a magnetostatic field to generate an electric current in tissue fluid to regulate the activities of neurons, has high spatial resolution and penetration depth. The neuronal spike-frequency adaptation plays an important role in the treatment of neural information. In this paper, we study the effects of ultrasonic intensity, magnetostatic field intensity and ultrasonic frequency on the neuronal spike-frequency adaptation based on the Ermentrout neuron model. The simulation results show that, the peak time interval becomes smaller, the interspike interval becomes shorter and the time of the firing of the neuron is shortened with the increasing of the magnetostatic field intensity. With the increase of the adaptive variables, the initial spike-frequency is shifted to the right with the magnetostatic field intensity, and the spike-frequency is linearly related to the increase of the magnetostatic field intensity in steady state. The simulation effect with change of the ultrasonic intensity is consistent with the change of magnetostatic field intensity. The change of the ultrasonic frequency has no effect on the neuronal spike-frequency adaptation. Under the different adaptive variables, with the increase of the adaptive variables, the initial spike-frequency amplitude decreased with the increasing of the ultrasonic frequency, and the spike-frequency is linearly related to the increase of the ultrasonic frequency in steady state. These results of the study can help us to reveal the mechanism of transcranial magneto-acoustical stimulation on the neuronal spike-frequency adaptation, and provide a theoretical basis for its application in the treatment of neurological disorders.
The phase-locking relationship between the firings of neuronal action potentials (i.e., spikes) and the oscillations of local field potentials (LFP) reflects important neural coding information. However, the present analysis methods can only determine whether there has phase-locking, but not the different strengths among various types of phase-locking. In the present paper, we used spike-triggered average (STA) signals and the percentage ratio (named φ) of the STA power to the power of original LFP as an index to evaluate the strengths of phase-locking. Experimental recordings obtained from rat hippocampal CA1 region as well as simulation data were used to evaluate the method. The results showed that the index φ changed monotonically as a function of the strength of phase-locking, and it could provide an effective critical value to divide phase-locking from non-phase-locking. Because the calculation of the index does not need pre-filtering, it can avoid the unwanted influences caused by intentionally limiting the frequencies of LFP oscillations such as in the traditional bin statistical method. Therefore, the index φ provides a novel method to investigate the mechanisms underlying neuronal coding in brain.
Recently a COVID-19 pneumonia pandemic caused by a novel coronavirus 2019-nCoV has broken out over the world. In order to better control the spread of the pandemic, there’s an urgent need to extensively study the virus’ origin and the mechanisms for its infectivity and pathogenicity. Spike protein is a special structural protein on the surface of coronavirus. It contains important information about the evolution of the virus and plays critical roles in the processes of cellular recognition and entry. In the past decades, spike protein has always been one of the most important objects in research works on coronaviruses closely related to human life. In this review we introduce these research works related to spike proteins, hoping it will provide reasonable ideas for the control of the current pandemic, as well as for the diagnosis and treatment of COVID-19.
ObjectivesTo explore the characteristics of cognitive deficits of Benign epilepsy of childhood with centrotemporal spikes (BECTS).MethodsA total of 61 BECTS patients who visited Neurology Clinic of Xuanwu Hospital Capital Medical University between September 2010 to December 2019 and 60 healthy controls were enrolled in our study. All patients and healthy controls performed a series of neuropsychological tests to assess their cognitive function in the "Multi-dimensional psychology" of Beijing Normal University, including attention; memory; arithmetic calculation; language processing; executive function; visuospatial processing; visual perception; psychomotor speed. Lastly, independent sample t-test and friedman test were performed on the scores of BECTS group and controls using SPSS 20.0 and we conducted a multi-factor comprehensive analysis of correlation between clinical criteria and cognitive dysfunction in BECTS.ResultsCompared with 60 healthy controls, the as group got an average score of 19.56±2.91 in Paired Association Learning Test (P<0.001), (23.67±9.50) in Word Discrimination Test (P=0.017), (61.45±13.14) in Object Quantity Perception Task (P=0.040), (6.54±1.47) in Digit Span Test (P<0.001), (5.79±5.90) in Vocal Perception Test (P<0.001), (35.10±2.33) in Taylor Complex Figure Test (P<0.001) and (700.34±493.053) (P=0.008) in Choice Reaction Time Test. The results of these tests are inferior to the control group and the remaining 10 tests are of no statistical significance. There were 36 children with onset of seizure before 8 years of age. Compared with the patients experienced onset of illness at a later age, the 36 patients exhibited lower scores in most of the neuropsychological tests including Visual Tracking Task, Spatial Memory Task, Simple Subtraction Task, Number Comparison Test, Language Rhyme Test, Word Discrimination Testand Visual Perception Task (P<0.05). 34 patients received monotherapy, and 27 received a combination of 2 or 3 anti-epileptic drugs. The scores of attention, memory, visual perception and reaction tests in the multi drug treatment group were lower than those in the single drug treatment group (P<0.05).ConclusionsChildren with BECTS have impairment in attention, vocal perception, visual perception, memory and psychomotor speed. The younger the age of onset, the more severe the cognitive impairments. The degree of cognitive deficitsinchildren treated with multi drugs was more serious than that of children treated with single drugs.
Deep brain stimulation (DBS) has been successfully used to treat a variety of brain diseases in clinic. Recent investigations have suggested that high frequency stimulation (HFS) of electrical pulses used by DBS might change pathological rhythms in action potential firing of neurons, which may be one of the important mechanisms of DBS therapy. However, experimental data are required to confirm the hypothesis. In the present study, 1 min of 100 Hz HFS was applied to the Schaffer collaterals of hippocampal CA1 region in anaesthetized rats. The changes of the rhythmic firing of action potentials from pyramidal cells and interneurons were investigated in the downstream CA1 region. The results showed that obvious θ rhythms were present in the field potential of CA1 region of the anesthetized rats. The θ rhythms were especially pronounced in the stratum radiatum. In addition, there was a phase-locking relationship between neuronal spikes and the θ rhythms. However, HFS trains significantly decreased the phase-locking values between the spikes of pyramidal cells and the θ rhythms in stratum radiatum from 0.36 ± 0.12 to 0.06 ± 0.04 (P < 0.001, paired t-test, N = 8). The phase-locking values of interneuron spikes were also decreased significantly from 0.27 ± 0.08 to 0.09 ± 0.05 (P < 0.01, paired t-test, N = 8). Similar changes were obtained in the phase-locking values between neuronal spikes and the θ rhythms in the pyramidal layer. These results suggested that axonal HFS could eliminate the phase-locking relationship between action potentials of neurons and θ rhythms thereby changing the rhythmic firing of downstream neurons. HFS induced conduction block in the axons might be one of the underlying mechanisms. The finding is important for further understanding the mechanisms of DBS.