Down syndrome (DS) is the most frequent autosomal aneuploidy. It is caused by the triplication of human chromosome 21. Disruption of the phenotype is the result of complex gene dosage imbalances regarding chromosome 21 and possibly other chromosomes. The typical DS phenotype is characterized by neurodevelopmental anomalies among which cognitive impairment is prevalent. In recent years, experimental attempts have been made to silence one supernumerary chromosome 21 and correct gene over expressions. They are promising but not practical in human beings. Cognitive pharmacotherapy targeting neurogenesis and synaptic connectivity is in its early stages. In spite of these advances, a complete cure of the condition is not reachable at the present stage and may never be possible given the short time available between syngamy and totipotent or multipotent stem cells in embryonic development. This means that one cannot dispense with behavioral interventions to normalize cognitive functioning in people with DS. The paper reviews current advances in the biomedical treatment of DS and specifies the course and contents of behavioral interventions in memory and language.

Studying sleep disorders is crucial due to their substantial influence on behavior and health in all age groups. The complex interplay of genetic, environmental, and lifestyle factors, including hormonal fluctuations, stress, and ozone exposure, is the cause of these disorders, which include insomnia, parasomnia, central hypersomnolence disorder, sleep-disordered breathing, and circadian rhythm sleep-wake disorders. They impact behavior, deteriorate social connections, and impair cognitive abilities, physical well-being, and emotional stability. The complex relationship between sleep and mental health frequently eludes attention, with approximately 17% of adults experiencing mental disorders during their lifetime. Frequently, insomnia is associated with anxiety and depression, indicating a bidirectional relationship. Conversely, individuals with mental health issues are susceptible to sleep disorders such as narcolepsy, restless legs syndrome, and sleep apnea. Treatment modalities such as relaxation therapy, stimulus control, and cognitive-behavioral therapy provide prospects for improvement, along with preventive measures such as maintaining a regular sleep schedule and exercising daily. The pandemic’s effect on sleep health has led to the introduction of terms such as “coronasomnia” and “COVID-somnia,” urging further studies on post-COVID-19 conditions. This review examines various sleep disorders, their effects, treatments, and the pandemic’s impact on sleep patterns, aiming to guide readers through the evolving landscape of sleep health during this global upheaval.

The morbidity and mortality associated with neonatal hypoxic-ischemic brain injury (HIBI) and the related clinical syndrome, hypoxic-ischemic encephalopathy (HIE), remain substantial. Consequently, treatment alternatives to therapeutic hypothermia, the current standard of care, are urgently needed. Therefore, unique aspects of the complex mechanistic underpinnings of neonatal HIBI and HIE must be studied. This review focuses on ferroptosis, a unique form of cell death, which was first described in 2012 and is characterized by iron-dependent lipid peroxidation, leading to lethal reactive oxygen species buildup. The role of ferroptosis in neonatal HIBI has been indirectly supported by decades of research and directly demonstrated using in vivo and in vitro models in recent years. Molecular targets, including nuclear factor erythroid 2-related factor 2, cystine/glutamate antiporter (system x_c^-), and glutathione peroxidase-4, have been identified as key mediators of ferroptosis in neonatal HIBI. In preliminary experiments, agents modulating the activity of these and other targets effectively suppress ferroptosis and attenuate the structural and functional consequences of neonatal HIBI. While considerable work is still required to establish the underlying mechanisms and therapeutic importance of these effects, the foundational studies show that antiferroptotic agents may reduce the lasting burden of neonatal HIBI and HIE.

Liquid- liquid phase separation (LLPS), once understood merely as a physicochemical phenomenon, has emerged over the past decade as a critical player in life processes. LLPS provides a novel framework for understanding the structure, function, and spatiotemporal regulation of intracellular biomolecules. Through LLPS, biomolecules within cells can spontaneously assemble into membraneless compartments, which allow precise regulation of biochemical reactions and influence critical cellular processes such as signal transduction and gene expression. Despite its recognized significance in basic biological research, the role of LLPS in human disease is still an area worthy of continued exploration. Currently, the most studied disorders in relation to LLPS are neurodegenerative diseases and cancer. In neurodegenerative diseases, LLPS is closely linked to protein misfolding and aggregation, processes that can lead to the formation of toxic assemblies, ultimately causing neuronal damage and death. In cancer, aberrant LLPS may contribute to the dysregulation of signaling pathways, promoting uncontrolled cell proliferation and metastasis. This review highlights recent advances regarding the role of LLPS in the pathogenesis of neurodegenerative diseases, discussing its function in these pathological conditions and proposing directions for future research. As research progresses, the potential role of LLPS in other human diseases will likely be uncovered, offering new avenues for diagnosis and therapy. Therefore, further investigation into the mechanisms of LLPS and its involvement in disease pathology will be crucial for advancing our understanding of human health and disease.

It is recommended that the assessment of cognitive function by occupational therapists is best conducted by observing the performance of everyday tasks in real-life environments. Given the constraints of acute care settings, selecting the appropriate cognition assessment for patients with traumatic brain injury (TBI) can be challenging. A scoping review was used to explore the evidence for occupation-based assessments of cognition for use with patients with TBI and explore their clinical applicability for the acute setting. Assessments were included if they focused on performance-based tests using real-life or simulated activities of daily living (ADL) or instrumental ADL tasks. From 29 identified articles, 18 occupation-based assessments of cognition were reported for use in patients with TBI. They varied in terms of time and resources required to administer, complexity, and variety of assessments. This review highlights a range of assessments of cognitive function available to patients with TBI in acute care, which support occupational therapists to use an occupation-centered approach. Issues faced by occupational therapists assessing cognitive function in the acute care setting include time and environmental constraints. A small number of portable, contemporary, and performance-based assessments relevant to younger adults warrant further investigation to determine their feasibility for use in acute care.

Since the beginning of the South London Stroke Register (SLSR) in 1995, stroke care has undergone major transformations and the SLSR adapted alongside. Recruitment strategies changed in line with patient pathways, and data collections were updated to reflect clinical practice and provide clinicians and policymakers with the most impactful data. Our Stroke Research Patient and Family group was pivotal to define the most relevant care and outcome measures for stroke survivors. The SLSR has published numerous studies on epidemiological trends and the implementation of care interventions. By providing real-world data, the SLSR has contributed to shaping local and national stroke policies, such as the UK’s National Audit Office reports 2005 and 2010, the reconfiguration of London’s stroke services and national stroke guidelines. Linking SLSR data with routinely collected health data might further address many unanswered questions around stroke as a long-term chronic condition in ageing populations.

Seizures are a hallmark of epilepsy and often lead to cognitive impairment. However, most antiepileptic medications have limited efficacy in this context and are associated with negative consequences with prolonged use. Tetrapleura tetraptera, an antioxidant-rich plant known for its anticonvulsant properties, prompted this study to examine its role in hippocampal protection after pentylenetetrazol (PTZ)-induced kindling. Phytochemical screening and median lethal dose assessments of the T. tetraptera fruit extract (TFE) were conducted. Forty-nine male Wistar rats (150 - 200 g, n=7 per group) were assigned as follows: Control, TFE (500 mg/kg), PTZ alone (40 mg/kg), and PTZ (40 mg/kg) following sodium valproate (200 mg/kg) or TFE at low (250 mg/kg), intermediate (500 mg/kg), and high (1,000 mg/kg) doses over 21 alternate days. PTZ was administered intraperitoneally, while all other treatments were given orally. On day 22, spontaneous alternation behavior (SAB) was assessed, followed by euthanasia and histological analyses. Phytochemical analysis of TFE identified phenols, alkaloids, and flavonoids as key constituents, and its oral median lethal dose was greater than 5,000 mg/kg. Pre-treatment with TFE showed suppressed seizures with quantal protection (p<0.05) compared to the PTZ group. While SAB was not significantly different, hippocampal Nissl expression was mildly affected, and neuron-specific enolase (NSE)-positive cells and glial fibrillary acidic protein (GFAP)-positive cells significantly decreased (p<0.05) compared with the control group. Therefore, oral administration of TFE is safe in Wistar rats with protection against PTZ-induced seizure and mortality. While short-term memory remained unaffected, the hippocampal Nissl substance, NSE, and GFAP were preserved, particularly in the low and intermediate TFE dose groups.

Mutations in the genes encoding TAR DNA-binding protein 43 (TDP43) or TANK-binding kinase 1 (TBK1) have been strongly associated with neurological disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. TDP43 is a key component of pathological protein aggregates found in more than 90% of ALS cases, while TBK1 plays a critical role in innate immune signaling and autophagy. Despite these associations, the precise molecular mechanisms linking TDP43 or TBK1 dysfunction to neurodegeneration remain poorly understood. The present study examined the impact of TDP43 on TBK1-mediated type I interferon (IFN1) production in HEK-293T cells. The findings demonstrated that co-expression of TDP43 and TBK1 resulted in a dose-dependent reduction in TBK1 and interferon regulatory factor (IRF) 7 protein levels. In addition, it led to decreased phosphorylation of IRF3 and TBK1. Interestingly, TDP43 knockout cells displayed elevated IRF7 protein levels. Moreover, co-expression of TDP43 and TBK1 significantly suppressed the IFN1 inductions and associated pro-inflammatory cytokines, a suppression reversed by IRF7 overexpression. Further, mechanistic analysis demonstrated that TDP43 facilitates TBK1 degradation through autophagy, resulting in diminished IFN1 induction. These findings uncover a new pathway through which TDP43 disrupts TBK1-mediated signaling through IRF7, potentially contributing to neurodegeneration. Overall, the disrupted TBK1-IRF7-IFN1 axis may therefore represent a critical pathway in TDP43-associated neurodegenerative diseases, offering potential targets for therapeutic intervention.

Cerebrospinal fluid (CSF) overdrainage syndrome occurs when excessive CSF drainage from the cranial cavity results from a spinal CSF leak or overdrainage through a ventriculoperitoneal (VP) or lumboperitoneal (LP) shunt. Symptoms include severe orthostatic headache, worsening with sitting or standing but improving when recumbent. The headache is typically dull, throbbing, and bilateral and may be exacerbated by Valsalva maneuver, coughing, or straining. Additional symptoms can include dizziness, nausea, vomiting, gait disturbances, diplopia, back pain, and seizures. We present a case of overdrainage syndrome following LP shunt placement for idiopathic intracranial hypertension in a 38-year-old woman with Ehlers-Danlos syndrome (EDS). One year post-surgery, she reported worsening headaches and nausea after prolonged upright positioning. Neurological examination revealed cerebellar dysfunction, including dysdiadochokinesia, intention tremor, and ataxic dysarthria. This condition gradually emerged 6 months post-LP shunt placement and was attributed to chronic overdrainage. After 1 day of observation, the patient underwent surgery to clamp the LP shunt outflow, resulting in overnight symptom resolution, including ataxic speech. This case underscores the importance of recognizing ataxic dysarthria in conjunction with low intracranial pressure syndromes, particularly in patients with EDS. It emphasizes the need to be aware of the diverse clinical manifestations of EDS and their relationship to altered CSF pressure syndromes.

Two genes likely to cause epilepsy, one silent and the other manifesting in a patient with drug-resistant epilepsy, can be quite unusual. Herein, we described the case of a 2-year-old girl who presented with predominant language development delay, facial dysmorphism, and refractory epilepsy with normal neuroimaging and metabolic profiles, which prompted us to consider genetic etiology. Her genetic test revealed two novel likely pathogenic mutations, in Mediator complex subunit 13-like (MED13L) and adhesion G protein-coupled receptor V1 (ADGRV1). Sanger sequencing of her parents revealed an ADGRV1 variant in her unaffected mother. The child had a phenotypic match with the MED13L genotype. However, only a few cases of MED13L have reported refractory epilepsy and the corresponding mutation was missense. To the best of our knowledge, this is the first case of frameshift mutation in MED13L presenting with refractory epilepsy. Although the child harbored two likely pathogenic mutations, the one inherited from her mother in ADGRV1 did not manifest, whereas the frameshift mutation in MED13L had expressed as refractory epilepsy, which has not been described hitherto.