Lipid droplets (LDs) are dynamic lipid storage organelles, derived from phospholipid monolayer membrane of the endoplasmic reticulum. LDs are composed of neutral lipids, mainly including triglycerides, sterol esters, and other non-polar lipids like cholesterol. The functions of LDs differ from different cell types in the central nervous system. The major role of LDs is to maintain lipid homeostasis, provide energy supply, and play a protective role in response to intracellular oxidative stress in the brain. Oxidative stress can lead to lipid dyshomeostasis, particularly the accumulation of LDs, followed by abnormal myelination, neuroinflammation, and cognitive decline. Neuroinflammation, aging, and age-related neurodegenerative disorders (NDDs) are characterized by the excessive accumulation of LDs in the brain. Although the LDs accumulation in the brain of the NDDs mouse model has been reported as early as a century ago, the role of LDs in the brain remains largely unknown. It is still unclear regarding the involvement of LDs accumulation in the pathogenesis of NDDs. In this review, we provide an overview of LDs biogenesis, the characteristics and functions of LDs from a cell-type perspective, and the pathological roles of LDs in NDDs on recent advances. In addition, we discuss the emerging LDs-based therapeutic strategies for NDDs, which may provide promising clues to develop novel therapeutic approaches for NDDs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with neurological effects that persist beyond the acute phase, collectively referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or “long COVID.” This article discusses the neurological impacts of PASC, which can occur regardless of the initial illness’s severity. Studies indicate that most patients continue to experience symptoms for at least 3 months post-infection. Long-term effects include neurocognitive deficits, sleep disturbances, and the exacerbation of pre-existing conditions. Proposed mechanisms underlying these effects include neuroinflammation, microvascular damage, and autoimmune responses, while direct viral neuroinvasion remains a topic of ongoing debate. SARS-CoV-2 may also worsen pre-existing neurological disorders and increase the risk of developing neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease. The article highlights the need for longitudinal studies to better understand the variability in outcomes and the mechanisms driving these persistent effects. In addition, it explores the inflammatory pathways linking long COVID to AD. Both conditions are characterized by chronic inflammation, activation of shared markers such as the NLR family pyrin domain containing 3 inflammasome, and alterations in amyloid-beta production. The apolipoprotein E4 gene, a known risk factor for AD, is also associated with more severe COVID-19 outcomes. Neuroimaging studies reveal brain changes in COVID-19 survivors, particularly in regions related to cognition and memory, further emphasizing the need for long-term research to assess the potential role of long COVID in exacerbating neurodegenerative diseases.

George Cotzias was a tireless physician who conducted a variety of studies, focusing mainly on neurological diseases. After leaving his medical studies to serve the Greek army voluntarily, Cotzias was relocated to the United States of America where he continued his studies at Harvard University. His first research was on hypertension, metabolism, and energy balance issues. Later on, he became the chief director of a project on chronic manganese poisoning. It was there that he identified the common characteristics between chronic manganese poisoning and Parkinson’s disease, which led him to be referred to the cyclotron. Furthermore, he noted the presence of dyskinetic, motor fluctuation abnormalities, and hypersensitivity caused by levodopa (L-DOPA). He was a pioneer in demonstrating the revolutionary practical benefits of L-DOPA therapy. This accomplishment was a consequence of his patience and insistence to monitor closely, even with cinematographic recording, the health condition of his patients while modifying the L-DOPA dose for optimal health benefit. Cotzias also developed drugs combining L-DOPA and dopamine agonists, defined the phenomenon of the brain’s ability to store chemical memory, and established the correlation between L-DOPA and cancer. His work significantly improved the lives and longevity of many individuals. Before his death from cancer in 1977, Cotzias received numerous distinctions and awards for his outstanding contributions to medicine. After his death, his legacy was honored through the establishment of various scholarships, professorships, conferences, and a movie dedicated to his medical achievements.

Innovative approaches are essential for treating central nervous system (CNS) diseases that present severe neurological manifestations and low survival rates. Delivering chemical or biological molecules across the blood-brain barrier (BBB) at therapeutically effective concentrations to treat CNS pathologies is a significant challenge. The urgent need for novel treatments targeting disease-causing proteins has propelled targeted protein degraders (TPDs) into the spotlight. TPDs have emerged as promising therapeutics for the treatment of CNS proteinopathies, characterized by the accumulation of misfolded protein aggregates. Given their structural features, the BBB permeability and CNS bioavailability of TPDs may seem improbable. However, several TPDs have demonstrated measurable concentrations in cerebrospinal fluid and the brain. Understanding the mechanisms behind their permeability across the BBB could open new avenues for the development of more effective TPD-based therapies for CNS proteinopathies. This review explores the absorption, distribution, metabolism, and excretion properties of TPDs in relation to brain pharmacokinetic parameters. It also delves into the likely interactions of advanced-stage TPDs with drug transporters and possibilities of disruption-propelled versus B-B barrier permeability-driven CNS bioavailability. Finally, it provides critical insights into the BBB permeability aspects of TPDs, uncovering new dimensions for future research.

The disclosure of an Alzheimer’s disease (AD) diagnosis is not always carried out following recognized bioethical principles. Inappropriate disclosing attitudes may induce unfortunate psychological impacts on the patients’ well-being, depriving them of an emotionally balanced adjustment to the condition. We present and discuss some examples of such inappropriate professional behavior, contradicting traditional medical teaching that “there are no diseases but patients.” We emphasize patient singularity and the need for a caring and empathy-driven approach to diagnostic disclosure. We underline the need to avoid emotionally charged terms at the time of disclosure and to provide cognitive, physical, and social interaction guidelines as prevention and containment strategies. We call for a revised approach on the appropriate disclosure of an AD diagnosis.

Performance validity testing (PVT) is crucial in contemporary neuropsychological assessment. This study aimed to validate several PVTs— - the Reliable Digit Span (RDS), the Longest Digit Forward-1 Trial, the Longest Digit Forward-2 Trials (LDF-2), the Tes Memori Jangka Pendek Indonesia (TMJPI), and the Non-Verbal Medical Symptom Validity Test - in an Indonesian mixed neurological sample. We recruited 141 patients through convenience sampling, divided into three groups: Neurocognitive disorder due to possible neurodegenerative disease (ND; n = 49), post-stroke (n = 42), and mixed etiology (n = 47). Data were collected prospectively. The PVT cut-off scores were adjusted when specificity rates fell below 0.90. Intercorrelations between Mini-Mental State Examination (MMSE) scores, demographic variables, and PVT scores were computed. The cut-off scores were modified for each group due to unacceptable specificity rates, with the most substantial adjustment made for the TMJPI cut-off score in the ND group. Three variables (MMSE, education, and age) were significantly correlated with PVT scores, with the exception of RDS and LDF-2. The PVTs were also significantly intercorrelated. We conclude that the previously developed Indonesian PVTs can be validly applied in neurological patients. However, clinicians should exercise caution when selecting PVTs and consider the demographic backgrounds of patients to minimize false-positive results.

Postural orthostatic tachycardia syndrome (POTS) is an autonomic condition characterized by sustained excessive postural tachycardia, often accompanied by a range of other symptoms of orthostatic intolerance, including heart palpitations, light-headedness, weakness, tremulousness, blurred vision, nausea, headache, dizziness and syncope. POTS predominantly affects young females. Little is known about the exact pathophysiology of this condition; however, preliminary reports about comorbidity profile of POTS suggest a possible link with functional disorders. The striking increase in functional tic-like behaviors (a specific phenotype of functional movement disorder) during the COVID-19 pandemic offered a privileged opportunity to further explore the possible association between POTS and functional neurological disorder. In the present study, we retrospectively assessed the prevalence of POTS in two large patient populations from a specialist clinic for tic disorders: (1) patients with neurodevelopmental tics who received a diagnosis of Gilles de la Tourette syndrome (GTS), and (2) patients who developed tic-like behaviors and received a diagnosis of functional tics since the onset of the COVID-19 pandemic (April 2020 - December 2024). The prevalence of POTS was 0/638 in the GTS group and 4/177 (2.3%) in the functional tics group. The four patients with POTS were females, with age at assessment ranging from 17 to 24 years. In addition to describing their clinical characteristics, we discuss the significance of the selective association between POTS and functional tic-like behaviors, in the absence of comorbidity between POTS and neurodevelopmental tics.

Epilepsy is a chronic neurological disorder affecting approximately 50 million people worldwide. Accurate and efficient detection of epileptic seizures is crucial for effective treatment and management. Electroencephalogram (EEG) signals, being non-invasive and rich in temporal information, are widely used for epilepsy diagnosis. However, manual inspection of EEG data is time-consuming and relies heavily on the expertise of clinicians. Machine learning techniques offer promising solutions for automating the classification of epileptic and non-epileptic EEG signals. In this study, we investigate the performance of various machine learning models - including Light Gradient Boosting Machine, deep learning architectures, and convolutional neural networks (CNN)—in classifying EEG signals for epilepsy detection. Our experiments demonstrate that CNN outperform other models due to their ability to capture complex spatial and temporal patterns inherent in EEG data. The CNN model achieved higher accuracy and better convergence, as evidenced by the confusion matrix and learning curves. In contrast, Deep Neural Networks without convolutional layers showed lower performance, likely due to their limitations in capturing the intricate features of EEG signals. Similarly, the Light Gradient Boosting Machine model exhibited good initial results but failed to generalize well to unseen data, possibly due to overfitting and lack of convergence. These findings highlight the potential of CNN-based approaches in the automated recognition of epileptic seizures using EEG signals, paving the way for more efficient and accurate diagnostic tools.

Patients with postural orthostatic tachycardia syndrome (POTS) typically present with a constellation of symptoms, some of which may mimic other disorders and may lead to misdiagnosis, including autonomic storms and autonomic movement disorders. We discuss two cases in which patients with POTS were misdiagnosed as functional neurological disorder. In both cases, the patients were initially misdiagnosed on hospital admission and then referred to neurologists, who correctly diagnosed them with POTS. We also review video evidence of these patients’ storms to showcase the visible presentation of POTS-related myoclonic episodes. Our study highlights the challenges of distinguishing POTS from other conditions due to overlapping, non-specific symptoms. In addition, this case series emphasizes the importance of a thorough clinical assessment, including an orthostatic assessment and tilt table testing, to ensure an accurate diagnosis. Misdiagnosis can delay appropriate management of POTS, highlighting the need for heightened awareness among clinicians when evaluating autonomic symptoms.

Arachnoid cysts are abnormal collections of fluids within the arachnoid membrane after a doubling of the structure. These benign lesions represent only 1% of all intracranial space-occupying lesions. The affected patient can remain asymptomatic for several years, which is an incidental finding in most cases. Cysts have been reported to rupture after a minor head trauma, causing subdural hygroma or hematoma; however, spontaneous rupture complicated with subdural hygroma has been rarely reported. Herein, we report a rare case of a 10-year-old boy whose pregnancy follow-up, delivery, and parent’s medical history were unremarkable. The patient was admitted for a temporal arachnoid cyst complicated with subdural hygroma, which was determined to be caused by intracranial hypertensive syndrome. He was successfully treated through endoscopic arachnoid cyst fenestration, wherein a pathway was created for the cyst to communicate with the subarachnoid space through the basal cisterns. The choice of treatment for arachnoid cysts remains controversial. Endoscopic treatment is considered when an ipsilateral subdural hygroma is present. Intracranial hypertensive syndrome subsided immediately after surgery. No post-operative complications occurred. The child recovered uneventfully in the post-operative period and was discharged 5 days after surgery. He underwent a follow-up computed tomography 1 month later, confirming a progressive regression of the hygroma as well as arachnoid cyst.