Abuse of amphetamine-based stimulants is a primary public health concern. Recent studies have underscored a troubling escalation in the inappropriate use of prescription amphetamine-based stimulants. However, the neurophysiological mechanisms underlying the impact of acute methamphetamine exposure (AME) on sleep homeostasis remain to be explored. This study employed non-human primates and electroencephalogram (EEG) sleep staging to evaluate the influence of AME on neural oscillations. The primary focus was on alterations in spindles, delta oscillations, and slow oscillations (SOs) and their interactions as conduits through which AME influences sleep stability. AME predominantly diminishes sleep-spindle waves in the non-rapid eye movement 2 (NREM2) stage, and impacts SOs and delta waves differentially. Furthermore, the competitive relationships between SO/delta waves nesting with sleep spindles were selectively strengthened by methamphetamine. Complexity analysis also revealed that the SO-nested spindles had lost their ability to maintain sleep depth and stability. In summary, this finding could be one of the intrinsic electrophysiological mechanisms by which AME disrupted sleep homeostasis.
Animals ; Methamphetamine ; Electroencephalography ; Male ; Sleep/drug effects* ; Central Nervous System Stimulants ; Delta Rhythm/drug effects* ; Sleep Stages/drug effects*

OBJECTIVES: To assess the regulatory effect of cannabidiol (CBD) on circadian rhythm sleep disorders following general anesthesia and explore its potential mechanism in a rat model of propofol-induced rhythm sleep disorder. METHODS: An electrode was embedded in the skull for cortical EEG recording in 24 male SD rats, which were randomized into control, propofol, CBD treatment, and diazepam treatment groups (n=6). Eight days later, a single dose of propofol (10 mg/kg) was injected via the tail vein with anesthesia maintenance for 3 h in the latter 3 groups, and daily treatment with saline, CBD or diazepam was administered via gavage; the control rats received only saline injection. A wireless system was used for collecting EEG, EMG, and body temperature data within 72 h after propofol injection. After data collection, blood samples and hypothalamic tissue samples were collected for determining serum levels of oxidative stress markers and hypothalamic expressions of the key clock proteins. RESULTS: Compared with the control rats, the rats with CBD treatment showed significantly increased sleep time at night (20:00-6:00), especially during the time period of 4:00-6:00 am. Compared with the rats in propofol group, which had prolonged SWS time and increased sleep episodes during 18:00-24:00 and sleep-wake transitions, the CBD-treated rats exhibited a significant reduction of SWS time and fewer SWS-to-active-awake transitions with increased SWS aspects and sleep-wake transitions at night (24:00-08:00). Diazepam treatment produced similar effect to CBD but with a weaker effect on sleep-wake transitions. Propofol caused significant changes in protein expressions and redox state, which were effectively reversed by CBD treatment. CONCLUSIONS CBD can improve sleep structure and circadian rhythm in rats with propofol-induced sleep disorder possibly by regulating hypothalamic expressions of the key circadian clock proteins, suggesting a new treatment option for perioperative sleep disorders.
Animals ; Rats, Sprague-Dawley ; Male ; Cannabidiol/therapeutic use* ; Rats ; Circadian Rhythm/drug effects* ; Propofol/adverse effects* ; Anesthesia, General/adverse effects* ; Sleep Wake Disorders/chemically induced* ; Hypothalamus/metabolism* ; Electroencephalography

OBJECTIVES: To study the factors influencing the short-term (28 days) efficacy of initial adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasms syndrome (IESS), as well as the factors influencing recurrence and prognosis. METHODS: The clinical data were collected from the children with IESS who received ACTH therapy for the first time in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from April 2008 to January 2018 and were followed up for ≥2 years. The multivariate logistic regression analysis was used to evaluate the factors influencing the short-term efficacy of ACTH therapy, recurrence, and long-term prognosis. RESULTS: ACTH therapy achieved a control rate of seizures of 55.5% (111/200) on day 28 of treatment. Of the 111 children, 75 (67.6%) had no recurrence of seizures within 12 months of follow-up. The possibility of seizure control on day 28 of ACTH therapy in the children without focal seizures was 2.463 times that in those with focal seizures (P<0.05). The possibility of seizure control on day 28 of ACTH therapy in the children without hypsarrhythmia on electroencephalography on day 14 of ACTH therapy was 2.415 times that in those with hypsarrhythmia (P<0.05). The possibility of recurrence within 12 months after treatment was increased by 11.8% for every 1-month increase in the course of the disease (P<0.05). The possibility of moderate or severe developmental retardation or death in the children without seizure control after 28 days of ACTH therapy was 8.314 times that in those with seizure control (P<0.05). The possibility of moderate or severe developmental retardation or death in the children with structural etiology was 14.448 times that in those with unknown etiology (P<0.05). CONCLUSIONS Presence or absence of focal seizures and whether hypsarrhythmia disappears after 14 days of treatment can be used as predictors for the short-term efficacy of ACTH therapy, while the course of disease before treatment can be used as the predictor for recurrence after seizure control by ACTH therapy. The prognosis of IESS children is associated with etiology, and early control of seizures after ACTH therapy can improve long-term prognosis.
Child ; Humans ; Infant ; Adrenocorticotropic Hormone/therapeutic use* ; Spasms, Infantile/drug therapy* ; Treatment Outcome ; Seizures ; Electroencephalography/adverse effects* ; Spasm/drug therapy*

Objective: To analyze the clinical features of children with uridine responsive developmental epileptic encephalopathy 50 (DEE50) caused by CAD gene variants. Methods: A retrospective study was conducted on 6 patients diagnosed with uridine-responsive DEE50 caused by CAD gene variants at Beijing Children's Hospital and Peking University First Hospital from 2018 to 2022. The epileptic seizures, anemia, peripheral blood smear, cranial magnetic resonance imaging (MRI), visual evoked potential (VEP), genotype features and the therapeutic effect of uridine were descriptively analyzed. Results: A total of 6 patients, including 3 boys and 3 girls, aged 3.5(3.2,5.8) years, were enrolled in this study. All patients presented with refractory epilepsy, anemia with anisopoikilocytosis and global developmental delay with regression. The age of epilepsy onset was 8.5 (7.5, 11.0) months, and focal seizures were the most common seizure type (6 cases). Anemia ranged from mild to severe. Four patients had peripheral blood smears prior to uridine administration, showing erythrocytes of variable size and abnormal morphology, and normalized at 6 (2, 8) months after uridine supplementation. Two patients suffered from strabismus, 3 patients had VEP examinations, indicating of suspicious optic nerve involvement, and normal fundus examinations. VEP was re-examined at 1 and 3 months after uridine supplementation, suggesting significant improvement or normalization. Cranial MRI were performed at 5 patients, demonstrating cerebral and cerebellar atrophy. They had cranial MRI re-examined after uridine treatment with a duration of 1.1 (1.0, 1.8) years, indicating significant improvement in brain atrophy. All patients received uridine orally at a dose of 100 mg/(kg·d), the age at initiation of uridine treatment was 1.0 (0.8, 2.5) years, and the duration of treatment was 2.4 (2.2, 3.0) years. Immediate cession of seizures was observed within days to a week after uridine supplementation. Four patients received uridine monotherapy and were seizure free for 7 months, 2.4 years, 2.4 years and 3.0 years respectively. One patient achieved seizure free for 3.0 years after uridine supplementation and had discontinued uridine for 1.5 years. Two patients were supplemented with uridine combined with 1 to 2 anti-seizure medications and had a reduced seizure frequency of 1 to 3 times per year, and they had achieved seizure free for 8 months and 1.4 years respectively. Conclusions: The clinical manifestations of DEE50 caused by CAD gene variants present a triad of refractory epilepsy, anemia with anisopoikilocytosis, and psychomotor retardation with regression, accompanied by suspected optic nerve involvement, all of which respond to uridine treatment. Prompt diagnosis and immediate uridine supplementation could lead to significant clinical improvement.
Male ; Female ; Humans ; Child ; Infant ; Epilepsy/genetics* ; Retrospective Studies ; Drug Resistant Epilepsy ; Uridine ; Evoked Potentials, Visual ; Anemia ; Electroencephalography/adverse effects* ; Neurodegenerative Diseases

OBJECTIVE: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. METHODS: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. RESULTS: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. CONCLUSION Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.
Adolescent ; Brain Diseases/complications* ; Cerebral Hemorrhage/complications* ; Child ; Electroencephalography ; Epilepsy/drug therapy* ; Female ; Humans ; Male ; Methotrexate/adverse effects* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prognosis ; Retrospective Studies

BackgroundRisperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.

MethodsNinety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups.

ResultsA total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.

ConclusionsBoth risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ.

Antipsychotic Agents ; pharmacology ; Brain-Derived Neurotrophic Factor ; drug effects ; China ; Electroencephalography ; Evoked Potentials ; drug effects ; Female ; Humans ; Male ; Paliperidone Palmitate ; pharmacology ; Risperidone ; pharmacology ; Schizophrenia ; drug therapy

The visual system plays an important role in our daily life. In this study, we found that loss of dendritic cell factor 1 (DCF1) in the primary visual cortex (V1) caused a sight deficit in mice and induced an abnormal increase in glutamic acid decarboxylase 67, an enzyme that catalyzes the decarboxylation of glutamate to gamma aminobutyric acid and CO, particularly in layer 5. In vivo electrophysiological recordings confirmed a decrease in delta, theta, and beta oscillation power in DCF1-knockout mice. This study presents a previously unknown function of DCF1 in V1, suggests an unknown contact between DCF1 and GABA systems, and provides insight into the mechanism and treatment of visual deficits.
Animals ; Brain Waves ; genetics ; Disease Models, Animal ; Electroencephalography ; Gene Expression Regulation ; drug effects ; genetics ; Geniculate Bodies ; drug effects ; metabolism ; Ginkgolides ; therapeutic use ; Glutamate Decarboxylase ; metabolism ; Lactones ; therapeutic use ; Membrane Proteins ; deficiency ; genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins ; deficiency ; genetics ; Photic Stimulation ; Proto-Oncogene Proteins c-fos ; metabolism ; Vision Disorders ; drug therapy ; genetics ; pathology ; physiopathology ; Visual Cortex ; metabolism ; pathology ; gamma-Aminobutyric Acid ; metabolism

Gamma band oscillation (GBO) and sensory gating (SG) are associated with many cognitive functions. Ketamine induces deficits of GBO and SG in the prefrontal cortex (PFC). However, the time-courses of the effects of different doses of ketamine on GBO power and SG are poorly understood. Studies have indicated that GBO power and SG have a common substrate for their generation and abnormalities. In this study, we found that (1) ketamine administration increased GBO power in the PFC in rats differently in the low- and high-dose groups; (2) auditory SG was significantly lower than baseline in the 30 mg/kg and 60 mg/kg groups, but not in the 15 mg/kg and 120 mg/kg groups; and (3) changes in SG and basal GBO power were significantly correlated in awake rats. These results indicate a relationship between mechanisms underlying auditory SG and GBO power.
Acoustic Stimulation ; Analysis of Variance ; Animals ; Dose-Response Relationship, Drug ; Electroencephalography ; Excitatory Amino Acid Antagonists ; pharmacology ; Gamma Rhythm ; drug effects ; Ketamine ; pharmacology ; Male ; Prefrontal Cortex ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sensory Gating ; drug effects ; Sleep Stages ; drug effects ; Statistics as Topic ; Time Factors ; Wakefulness ; drug effects

BACKGROUNDBispectral index (BIS) is considered very useful to guide anesthesia care in elderly patients, but its use is controversial for the evaluation of the adequacy of analgesia. This study compared the BIS changes in response to loss of consciousness (LOC) and loss of somatic response (LOS) to nociceptive stimuli between elderly and young patients receiving intravenous target-controlled infusion (TCI) of propofol and remifentanil.

METHODSThis study was performed on 52 elderly patients (aged 65-78 years) and 52 young patients (aged 25-58 years), American Society of Anesthesiologists physical status I or II. Anesthesia was induced with propofol administered by TCI. A standardized noxious electrical stimulus (transcutaneous electrical nerve stimulation, [TENS]) was applied (50 Hz, 80 mA, 0.25 ms pulses for 4 s) to the ulnar nerve at increasing remifentanil predicted effective-site concentration (Ce) until patients lost somatic response to TENS. Changes in awake, prestimulus, poststimulus BIS, heart rate, mean arterial pressure, pulse oxygen saturation, predicted plasma concentration, Ce of propofol, and remifentanil at both LOC and LOS clinical points were investigated.

RESULTSBISLOCin elderly group was higher than that in young patient group (65.4 ± 9.7 vs. 57.6 ± 12.3) (t = 21.58, P < 0.0001) after TCI propofol, and the propofol Ce at LOC was 1.6 ± 0.3 μg/ml in elderly patients, which was significantly lower than that in young patients (2.3 ± 0.5 μg/ml) (t = 7.474, P < 0.0001). As nociceptive stimulation induced BIS to increase, the mean of BIS maximum values after TENS was significantly higher than that before TENS in both age groups (t = 8.902 and t = 8.019, P < 0.0001). With increasing Ce of remifentanil until patients lost somatic response to TENS, BISLOSwas the same as the BISLOCin elderly patients (65.6 ± 10.7 vs. 65.4 ± 9.7), and there were no marked differences between elderly and young patient groups in BISawake, BISLOS, and Ce of remifentanil required for LOS.

CONCLUSIONIn elderly patients, BIS can be used as an indicator for hypnotic-analgesic balance and be helpful to guide the optimal administration of propofol and remifentanil individually.

TRIAL REGISTRATIONCTRI Reg. No: ChiCTR-OOC-14005629; http://www.chictr.org.cn/showproj.aspx?proj=9875.

Adult ; Aged ; Electroencephalography ; drug effects ; Female ; Humans ; Male ; Middle Aged ; Movement Disorders ; physiopathology ; Pain ; physiopathology ; Piperidines ; pharmacology ; Propofol ; pharmacology ; Transcutaneous Electric Nerve Stimulation ; Unconsciousness ; physiopathology

Adult ; Anticonvulsants ; therapeutic use ; Brain ; drug effects ; pathology ; physiopathology ; Carbamazepine ; analogs & derivatives ; therapeutic use ; Electroencephalography ; Epilepsy, Frontal Lobe ; diagnosis ; drug therapy ; Female ; Humans ; Myoclonic Epilepsy, Juvenile ; diagnosis ; drug therapy ; Myoclonus ; diagnosis ; drug therapy