Cerebrovascular disease is uncommon in patients with HIV, occurring in up to 1.9% of patients, 0.2% were presenting with transient ischemic attacks. The central nervous system is the first part of the body to be affected by the human immunodeficiency virus. This case report is a unique presentation of a 33-year-old male who presented with focal neurologic deficits that lasted for one hour with a background of promiscuous history. The patient was positive for HIV screening test and CD4 count and was started on a combination of antiretroviral therapy. This is the first documented case report in the Philippines. This case report demonstrates the need for a high index of suspicion for early detection of the cause in HIV-positive patients with recurrent transient ischemic attacks, given the high morbidity and mortality that is associated with this condition if delayed or undiagnosed.

Antisense oligonucleotide (ASO) was discovered several decades ago and initially used only as a research tool in the laboratory. In recent years, several ASO therapeutics have been developed for neurological disorders. Some of these therapeutics, including eteplirsen, golodirsen, viltolarsen, nusinersen and inotersen, have been approved by the Food and Drug Administration (FDA) and begun to draw the public's attention as an effective therapeutic approach. These novel therapeutics have shown great performance, while many similar therapeutics are under investigation and in clinical trials. This n-of-1 precision medicine may start a new chapter in the paradigm of therapeutics. Clinicians, clinical geneticists, and genetic counselors may know about this novel therapy, but very few may understand the background in details. During genetic counseling, they have the responsibility to convey the effectiveness, side effects and cost of such therapies to patients and their families. As these target therapies will require precise genetic diagnosis before treatment, healthcare professionals and genetic counselors play a vital role in relating the patients to the corresponding ASO drugs. This review has elaborated the mechanism of ASO therapies, including basic rationales, modifications, side effects and delivery routes. It also systemically summarized the FDA-approved ASO therapeutics and their applications for various neurological disorders, and discussed the limitations and challenges the real-world market may face and issues genetic counselor should take into consideration in the near future.
Humans ; Oligonucleotides, Antisense/therapeutic use* ; Nervous System Diseases/drug therapy* ; Genetic Therapy/methods*

OBJECTIVE: To explore the clinical characteristics and genetic cause of a child with gastrointestinal hemorrhage and Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) and to review the literature. METHODS: Clinical data of a child with gastrointestinal hemorrhage with CRMCC admitted to the Hepatology Department of Hunan Children's Hospital in September 2019 were collected, and peripheral blood DNA of the child and his parents were analyzed by whole exome sequencing. Candidate variants were validated by Sanger sequencing, followed by bioinformatics analysis, American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants pathogenicity classification, and protein structure prediction. A literature search with "Coats Plus syndrome" or "Cerebroretinal microangiopathy with calcifications and cysts" as keywords was conducted at PubMed, China National Knowledge Infrastructure and Wanfang databases to include recently published studies (up to December 2023). This study has been approved by the Ethics Committee of Hunan Children's Hospital (Ethics No. KY2020-07). Informed consent for clinical research was obtained from the guardian of the child. RESULTS: The proband was a 10-year-10-month-old boy. The clinical manifestations were intrauterine and postnatal growth retardation, gastrointestinal hemorrhage, liver fibrosis, panhemopenia, bilateral exudative retinopathy, intracranial lesions and facial pigmentation. WES and Sanger sequencing revealed two novel heterozygous variants in the CTC1 gene: c.787G>A (p.Val263Met) in exon 5 and c.2930C>G (p.Ser977Cys) in exon 17, which were inherited from his mother and father, respectively. According to ACMG pathogenicity classification, both missense variants were classified as variants of uncertain significance (VUS). Protein structure prediction showed the absence of LIG_SH3_3 motif and LIG_SH3_3 motif, and the p.Ser977Cys mutation may affect the binding between CST (CTC1-STN1-TEN) complex and DNA strand. The child had continued to experience recurrent gastrointestinal bleeding episodes despite propranolol treatment, but the condition was controlled after liver transplantation. According to the predefined literature search strategy of this study, a total of 10 relevant articles on pediatric CRMCC patients were retrieved, involving 11 children with gastrointestinal bleeding. Pharmacological and endoscopic therapies play a certain role in the management of CRMCC children complicated with gastrointestinal bleeding. CONCLUSION The CTC1 gene c.787G>A and c.2930C>G variants probably underlay CRMCC in this child. This study has broadened the variation spectrum of CTC1-related diseases and provided a basis for genetic counseling. Liver transplantation may be an important treatment for gastrointestinal hemorrhage in children who do not respond well to medication and endoscopic therapy.
Humans ; Male ; Gastrointestinal Hemorrhage/genetics* ; Child ; Calcinosis/genetics* ; Cysts/genetics* ; Central Nervous System Cysts/genetics* ; Mutation ; Exome Sequencing ; Leukoencephalopathies ; Retinal Diseases ; Seizures ; Muscle Spasticity ; Brain Neoplasms ; Ataxia

Myelin formation is considered the last true "invention" in the evolution of vertebrate nervous system cell structure. The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement, sensation, and cognitive function. As a key structure in the brain, white matter is the gathering place of myelin. However, with age, white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes, causing serious neurological and cognitive disorders. Despite the extensive time and effort invested in exploring myelination and its functions, numerous unresolved issues and challenges persist. In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system (CNS) diseases and even mental illnesses. In this study, we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS, delving into its formation process. Specifically, we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension. The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.
Myelin Sheath/metabolism* ; Humans ; Central Nervous System/metabolism* ; Animals

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*

This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.
Humans ; Cerebral Small Vessel Diseases/pathology* ; Inflammation/pathology* ; Cerebral Amyloid Angiopathy/pathology* ; Vasculitis, Central Nervous System/pathology* ; Vasculitis/pathology*

This study examined the regulatory effects of autonomic nervous system on aerobic endurance exercise performance in cold exposure, focusing on heart rate recovery (HRR) and heart rate variability (HRV) across genders. Thirty participants (17 males and 13 females) from a university track endurance program, classified as exercise grade II or above, underwent monitoring of HRV in time domain, frequency domain, nonlinear correlation indices and 1 min HRR. Measurements were taken before, during, and after aerobic endurance exercise in cold and normal environments, respectively. The results were as follows. (1) The duration of aerobic endurance exercise completed by all the subjects in cold environment was significantly increased compared with that in normal environment. The 1 min HRR after aerobic endurance exercise in cold environment was significantly lower than that in normal environment, and the decrease in the males was significantly higher than that in the females. (2) The time domain analysis results showed that, prior to the aerobic endurance exercise, there were no significant difference of standard deviation from the mean value of normal to normal intervals (SDNN), root mean square of successive differences (RMSSD), and percentage of adjacent normal-to-normal intervals differing by more than 50 ms (pNN50) between cold and normal environments. During aerobic endurance exercise in cold environment, SDNN, RMSSD and pNN50 were significantly higher than those in normal environment, with the females showing significantly greater increases compared with those of the males. The levels of SDNN, RMSSD and pNN50 in the males at different time points under different environments were significantly lower than those in the quiet state; The levels of SDNN and RMSSD of the females at different time points under different environments were significantly lower than those in the quiet state, while the pNN50 at different time points under cold environments was significantly lower than that in the quiet state. (3) Frequency domain analysis results showed that, prior to the aerobic endurance exercise, there was no significant difference of high frequency normalized units [HF (n.u.)], low frequency normalized units [LF (n.u.)] and LF/HF ratio between cold and normal environments. During aerobic endurance exercise in cold environment, the levels of HF (n.u.) significantly increased compared to normal environment in the females, while LF (n.u.) and LF/HF ratio levels significantly decreased compared to normal environments. The levels of HF (n.u.), LF (n.u.) and LF/HF ratio of different genders at different time points in the different environments showed no significant changes, compared to those in the quiet state. (4) Non-linear analysis results showed a significant increase in SD1 (standard deviation perpendicular to the line-of-identity)/SD2 (standard deviation along the line-of-identity) ratio during aerobic endurance exercise in cold environment in the females, while no significant changes were observed in the males. SD1/SD2 ratios in the males at different time points and in the females at 1 min under cold environments were significantly higher than those in the quiet state. These findings suggest that aerobic endurance performance increases during cold exposure, accompanied by gender-specific differences in the regulation of autonomic nervous system. Females exhibit higher vagal activity and faster autonomic nervous system recovery compared to males.
Humans ; Male ; Female ; Heart Rate/physiology* ; Cold Temperature ; Exercise/physiology* ; Physical Endurance/physiology* ; Autonomic Nervous System/physiology* ; Young Adult ; Adult ; Sex Factors

The nucleus tractus solitarius (NTS) is the primary brain region for receiving and integrating cardiovascular afferent signals. It plays a crucial role in maintaining balance of autonomic nervous system and regulating blood pressure through cardiovascular reflexes. Neurons within the NTS form complex synaptic connections and interact reciprocally with other brain regions. The NTS regulates autonomic nervous system activity and arterial blood pressure through modulating baroreflex, sympathetic nerve activity, renin-angiotensin-aldosterone system, and oxidative stress. Dysfunctions in NTS activity may contribute to hypertension. Understanding the NTS' role in centrally regulating blood pressure and alterations of neurotransmission or signaling pathways in the NTS may provide rationale for new therapeutic strategies of prevention and treatment. This review summarizes the research findings on autonomic nervous system regulation and arterial blood pressure control by NTS, as well as unresolved questions, in order to provide reference for future investigation.
Solitary Nucleus/physiopathology* ; Hypertension/physiopathology* ; Humans ; Animals ; Autonomic Nervous System/physiopathology* ; Blood Pressure/physiology* ; Baroreflex/physiology* ; Renin-Angiotensin System/physiology* ; Sympathetic Nervous System/physiology*

The etiology of nervous system diseases is complicated, posing significant harm to patients and often resulting in poor prognoses. In recent years, the role of dopaminergic system in nervous system diseases has attracted much attention, and its complex regulatory mechanism and therapeutic potential have been gradually revealed. This paper reviews the role of dopaminergic neurons, the neurotransmitter dopamine, dopamine receptors and dopamine transporters in neurological diseases (including Alzheimer's disease, Parkinson's disease and schizophrenia), with a view to further elucidating the disease mechanism and providing new insights and strategies for the treatment of neurological diseases.
Humans ; Dopamine/metabolism* ; Nervous System Diseases/physiopathology* ; Parkinson Disease/physiopathology* ; Receptors, Dopamine/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Alzheimer Disease/physiopathology* ; Schizophrenia/physiopathology* ; Animals

BACKGROUND

Heart rate variability (HRV) is a common tool for assessing autonomic nervous system activity and monitoring training load in athletes. However, limited research has explored how HRV responds to different forms of resistance training, particularly in high-intensity intermittent sports like basketball and football.

This study aims to compare the acute HRV responses between neuromuscular and metabolic training in collegiate athletes involved in high-intensity intermittent sports.

A comparative cross-sectional study with a quasi-experimental crossover design will be employed.

Collegiate athletes will be randomly assigned to undergo both neuromuscular and metabolic training sessions with a one-week wash-out period in between. HRV data will be recorded using the Polar H10 chest strap during each session.

Descriptive statistics will summarize salient participant characteristics and HRV measurements. Inferential analysis will use paired t-tests or Wilcoxon signed-rank tests based on normality, assessed via the Kolmogorov-Smirnov test. All statistical analyses will be conducted using the IBM SPSS (ver.25) with a confidence interval set. at 95% and a critical α equal to 0.05.

Neuromuscular training is expected to elicit higher low-frequency (LF) power and an increased LF/HF ratio, reflecting greater sympathetic activation, while metabolic training is expected to show lower LF power and a decreased LF/HF ratio, indicating a more balanced autonomic response. These findings will offer insights into the differential autonomic impacts of these training modalities.