Brain Involvement Research Articles

Brain metastases during follow-up of patients with resected cutaneous melanoma.

Melanoma is among the most common tumors that disseminate to the brain. We analyzed patients with resected early-stage cutaneous melanoma who developed sole brain metastases and brain metastases accompanying other organ spreads and interpreted the clinical characteristics of these patients in this study. A total of 457 patients who developed any organ metastases during or after adjuvant therapy or in follow-up were included in the analysis. A total of 55 (12%) patients had brain metastases (M1d), and 402 patients had other (M1a,b,c) metastases. The majority of brain metastases (n = 36, 65.4%) were accompanied by other organ metastases, only 19 patients had sole brain metastases. Brain metastases were mostly in men (76.4 vs. 61.9%, P = 0.03), and extracerebral dissemination was more commonly associated with acral lentiginous melanoma histopathology (16.7 vs. 4.7%, P = 0.04). Brain metastasis was found to be associated with shorter survival (median survivals were 6.0 vs. 12.45 months, respectively, P = 0.0001). However, there was no difference in survival between patients with isolated brain involvements and patients with brain metastases accompanied by spread to other organs (median survivals were 6.0 vs. 5.85 months, respectively, P = 0.1). In conclusion, brain metastases are a very small portion of relapsed melanoma patients, and the numbers of isolated brain metastases are even smaller, thus the significance of routine brain scans for early detection of brain involvement in the follow-up of patients might be questionable and unnecessary.

Simultaneous involvement of Brain and Peripheral nerves in a Child with Systemic lupus erythematosus (SLE): A Case Report

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects almost every system in the body. Neuropsychiatric symptoms are common in SLE, but diagnosis often remains difficult. In this case, we report a girl of 16 years who presented with an acute confusional state and features of peripheral neuropathy. A detailed clinical evaluation with a review of the medical history and appropriate laboratory analyses allows this diagnosis to be made. Treatment with immune-modulating therapy, cyclophosphamide resulted in significant improvement of her symptoms. Neuropsychiatric SLE should be considered a potential differential diagnosis for patients presenting with acute confusional state and peripheral neuropathy. J Bangladesh Coll Phys Surg 2025; 43: 89-92

Reduced white matter integrity and disrupted brain network in children with type 2 and 3 spinal muscular atrophy

BackgroundSpinal muscular atrophy (SMA) is caused by reduced expression of survival motor neuron (SMN) protein. Previous studies indicated SMA causes not only lower motor neuron degeneration but also extensive brain involvement. This study aimed to investigate the changes of brain white matter and structural network using diffusion tensor imaging (DTI) in children with type 2 and 3 SMA.MethodsForty-two type 2 and 3 pediatric SMA patients and 42 age- and gender-matched healthy controls (HC) were prospectively enrolled in this study. The tract-based spatial statistics (TBSS) was used to assess white matter integrity and the structural network properties were calculated based on DTI white matter fiber tracking and the graph theory approach. A partial correlation was performed to explore the relationship between white matter parameters and clinical characteristics.ResultsIn total, 42 patients (mean age, 10.86 ± 4.07 years; 23 men) were included. TBSS analysis revealed widespread white matter changes in SMA patients. The SMA patients showed changes in multiple small-world and network efficiency parameters. Compared to the HC group, SMA showed increased characteristic path length (Lp), normalized clustering coefficient (γ), small-world characteristic (σ), and decreased global efficiency (Eglob) (all p < 0.05). In the node properties, right supramarginal gyrus, right orbital part of superior frontal gyrus, right supplementary motor area, and left median cingulate and paracingulate gyri changed in SMA patients. A decreased axial diffusivity (AD) value was associated with lower Hammersmith Functional Motor Scale-Expanded scores (r = 0.45, p = 0.02), which means that the symptoms of SMA patients are more severe.ConclusionsThis study found white matter and DTI-based brain network abnormalities in SMA patients, suggesting SMN protein deficiency may affect white matter development.

Evaluation of Hydatid Cyst Cases: A Single-center Retrospective Study.

Cystic echinococcosis (CE) is a zoonotic condition that can be encountered, particularly in developing countries, and leads to significant economic losses. This study was planned to observe the treatment options, complications, in the patients we followed. Patients aged 18 and over who were diagnosed with hydatid cyst and followed in our hospital between January 2018 and December 2023 were included in the study. Data were obtained from the hospital's record system. The patients with CE were retrospectively evaluated in terms of age, gender, cyst location, treatment method applied, presence of relapse, and complications. A total of 30 patients, with a mean age of 42.8 years (range: 19-68), were included in the study; 13 (43.3%) were male and 17 (56.7%) were female. The most common presenting complaint was abdominal pain (n=14, 46.7%), and 6 patients (20.0%) were asymptomatic. Sixteen patients had multiple cysts in the same region, and 6 patients had cysts in different regions. The most common site of involvement was the liver (n=21, 70.0%), followed by the lungs in 4 patients (13.3%). Single cases of brain, spinal cord, spleen, kidney, and bone involvement were observed. Diagnosis was made by ultrasonography in 16 patients (53.3%), magnetic resonance imaging in 8 patients (26.7%), and computed tomography in 6 patients (20.0%). Surgical intervention was performed in 20 patients (66.7%), and percutaneous drainage in 3 patients (10.0%). All patients received albendazole treatment. Complications included intra-abdominal abscess in three patients (10.0%) and rupture in one patient. One patient with intracranial involvement died. Although observed worldwide, CE maintain their importance in terms of morbidity and mortality, particularly in developing countries.

Central Involvement in Pure Autonomic Failure: Insights from Neuromelanin-Sensitive Magnetic Resonance Imaging and 18F-Fluorodopa-Positron Emission Tomography.

Central synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), involve alpha-synuclein accumulation and dopaminergic cell loss in the substantia nigra (SN) and locus coeruleus (LC). Pure autonomic failure (PAF), a peripheral synucleinopathy, often precedes central synucleinopathies. To assess early brain involvement in PAF using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and fluorodopa-positron emission tomography (FDOPA-PET), and to determine whether PAF patients with a high likelihood ratio (LR) for conversion to a central synucleinopathy exhibit reduced NM-MRI contrast in the LC and SN compared with controls and low-LR patients. Participants with PAF (n = 23) were categorized as high-LR (n = 13) or low-LR (n = 10) for conversion to central synucleinopathy. Additional participants included PD (n = 22), DLB (n = 8), and age- and sex-matched healthy controls (n = 23). NM-MRI at 3 T was used to quantify contrast ratios in the LC and SN, while FDOPA-PET measured presynaptic dopamine synthesis. Linear regression analyses, adjusted for age and sex, were used to compare NM-MRI contrast across groups. High-LR PAF patients showed reduced contrast in the LC and SN compared with controls and low-LR PAF patients, with values similar to PD and DLB. The NM-MRI contrast in the SN correlated with dopamine uptake in the striatum. Longitudinal imaging in PAF patients (n = 6) demonstrated reduced NM-MRI and PET values in individuals who developed central synucleinopathies. NM-MRI and FDOPA-PET may serve as potential biomarkers for early brain involvement and predicting progression to central synucleinopathies in PAF and could help identify patients for early intervention. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Differences in the Lateralization of Theta and Alpha Power During n-Back Task Performance Between Older and Young Adults in the Context of the Hemispheric Asymmetry Reduction in Older Adults (HAROLD) Model

Hemispheric Asymmetry Reduction in Old Adults (HAROLD) is one of the most well-known models of compensatory brain involvement in older adults. Most evidence supports its occurrence from the perspective of PET and fMRI studies, with a deficiency in electroencephalographic research in this domain. Therefore, we aimed to investigate the possibility of identifying the HAROLD pattern in older adults’ power of theta and alpha. The study sample comprised 50 older adults and 60 young adults performing n-back tasks while recording EEG signals. The level of cognitive performance and the theta and alpha power for pairs of symmetrical electrodes in the prefrontal, frontal, and parietal areas were analyzed. Older adults exhibited inferior cognitive performance compared to young adults and heightened theta power in the right hemisphere within the prefrontal and parietal areas. However, they also demonstrated increased alpha power in the right frontal pole, which contradicts the compensatory effects of theta power. Moreover, the two indicated phenomena of lateralization of theta and alpha power in older adults were unrelated to individual cognitive performance. The results make it challenging to discern whether the revealed age-related differences in theta and alpha power lateralization denote compensation, dedifferentiation, or nonselective recruitment as neutral features of brain activity in old adults.

LATE, Hippocampal Sclerosis, and Primary Age-related Tauopathy

ABSTRACT OBJECTIVE Although Alzheimer disease (AD) is the most common neurodegenerative cause of dementia, neurologists must be aware of other etiologies that can mimic the amnestic-predominant syndrome and medial temporal brain involvement typically associated with AD. This article reviews recent updates surrounding limbic-predominant age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy (LATE), hippocampal sclerosis, and primary age-related tauopathy. LATEST DEVELOPMENTS LATE neuropathologic change occurs in approximately 40% of autopsied older adults, including occurrences in isolation in some older individuals with amnestic cognitive impairment. LATE neuropathologic change is often, but not always, associated with hippocampal sclerosis (neuronal loss and gliosis in the hippocampus and associated structures) and frequently coexists with AD and other neurodegenerative pathologies. Although there is no direct clinical biomarker for TDP-43 pathology, recent studies suggest that a clinical diagnosis of LATE can be achieved through the integration of multiple data points. Primary age-related tauopathy refers to the pathologic finding (in some cognitively unimpaired older adults as well as some individuals with cognitive impairment) of medial temporal–predominant neurofibrillary tangles in the absence of amyloid-β (Aβ) plaques. Recent consensus frameworks have attempted to resolve ambiguities of nomenclature and diagnosis for these entities, and efforts toward in vivo biomarkers are ongoing. ESSENTIAL POINTS LATE, with or without hippocampal sclerosis, and primary age-related tauopathy belong in the differential diagnosis (along with AD, argyrophilic grain disease, and other disorders) for slowly progressive amnestic-predominant cognitive impairment, particularly in individuals older than 75 years. Accurate recognition of clinical and diagnostic test features supportive of these non-AD entities is vital to optimize patient counseling, therapeutic selection, and novel biomarker development.

R183Q GNAQ Sturge–Weber Syndrome Leptomeningeal and Cerebrovascular Developmental Mouse Model

Objective(s): Sturge–Weber syndrome (SWS), a rare neurovascular malformation disorder, is usually caused by the R183Q GNAQ somatic mosaic mutation enriched in brain endothelial cells. A developmental mouse model of SWS brain involvement is needed to investigate mutation impact upon brain vascular development and to facilitate preclinical drug studies. Methods: A new Tet-ON R183Q GNAQ transgenic mouse line was paired with rtTA tet transactivator mice under the Tie2 promoter to generate mice expressing endothelial R183Q GNAQ in the presence of doxycycline. Litters were perfused at P14-17; half received a subseizure dose (1.5 mg/kg; intraperitoneal) of kainate an hour before perfusion. A subset was perfused with Evans blue. Fixed mouse brains were stained with X-gal, DAPI, and antibodies for Gαq, Tie2, phosphorylated-S6, and claudin-5. Images were scored for vessel staining intensity. Results: X-gal staining was seen only in mutant mice; leptomeningeal endothelial X-gal staining was more frequent in kainate-treated mice (P &lt; 0.001). When perfused with Evans blue, only mutant brains showed severe staining (P = 0.028). Median phosphorylated-S6 vessel scores were significantly higher in the leptomeninges of mutant mice (P = 0.035). Mutant cortical microvessels demonstrated discontinuous claudin-5 and phosphorylated-S6 staining as well as increased vessel length in kainate-treated mice (P = 0.024). Conclusions: The new R183Q GNAQ Tet-ON developmental mouse brain model of SWS demonstrates endothelial expression of mutant Gαq associated with blood–brain barrier breakdown, altered vascular mammalian target of rapamycin activity, and abnormal cortical microvessel structure. This new translational model can be used to develop new drug targets and treatments for SWS.

Paternal, Maternal, and Familial Factors as Predictors of Sturge–Weber Syndrome Neurological Outcome

Objectives: To identify potential risk factors influencing Sturge–Weber Syndrome (SWS) and neurological outcomes in individuals with SWS and port-wine birthmarks from paternal, maternal, and familial factors. Methods: This study follows a retrospective cross-sectional design. Clinical visits took place at the Kennedy Krieger Institute, a tertiary care center. Participants were individuals with SWS or port-wine birthmarks. Results: Higher paternal age at conception was associated with a range of cognitive dysfunctions in offspring with SWS brain involvement. Indeed, paternal age was associated with low intelligence quotient (n = 25, P = .004), strokes or stroke-like episodes (n = 34, P = .030), gross and/or fine motor delay (n = 34, P = .036), delays in ability to perform activities of daily living (n = 30, P = .012), and delayed learning compared to peers (n = 31, P = .027). Furthermore, paternal age was correlated with worse cognitive outcomes, as measured by cognitive Neuroscore (r s = 0.575, P &lt; .001, n = 32). When maternal thyroid disease and hypertension were present during pregnancy, offspring were more likely to experience low intelligence quotient (n = 30, P = .041) and regression of any abilities (n = 37, P = .045), respectively. Logistic regression confirmed the association between paternal age and severe cognitive Neuroscore (β = .580, P = .033, odds ratio: 1.79, 95% confidence interval: 1.05–3.04), even when controlling for the effects of seizures and strokes or stroke-like episodes. Conclusions: Prenatal factors were associated with neurological symptoms in subjects with SWS. Older paternal age, in particular, may predict worse neurocognitive outcomes. Further research is needed in larger cohorts to determine the value of the identified prenatal factors as prognostic tools. Likewise, animal models may be used to determine the impact of prenatal factors on the severity of outcome.

Machine Learning Reveals Aneuploidy Characteristics in Cancers: The Impact of BEX4.

Aneuploidy is crucial yet under-explored in cancer pathogenesis. Specifically, the involvement of brain expressed X-linked gene 4 (BEX4) in microtubule formation has been identified as a potential aneuploidy mechanism. Nevertheless, BEX4's comprehensive impact on aneuploidy incidence across different cancer types remains unexplored. Patients from The Cancer Genome Atlas (TCGA) were stratified into high-score (training) and low-score (control) groups based on the aneuploidy score. Mfuzz expression pattern clustering and functional enrichment were applied to genes with BEX4 as the core to explore their regulatory mechanisms. Various machine learning techniques were employed to screen aneuploidy-associated genes, after which aneuploidy characteristic subtypes were established in cancers. Moreover, the aneuploidy characteristics across multiple cancer types were investigated by integrating the extent of tumor cell stemness acquisition and a series of immune traits. Immunohistochemistry and proliferation assay mainly verified the anti-tumor effect of different BEX4 level. Functional clustering results showed that aneuploidy and stemness were significantly associated in kidney chromophobe (KICH) and thyroid carcinoma (THCA). And cell metabolism and cell cycle had key effects. Residual analysis indicates superior screening performance by random forest (RF). An aneuploid feature gene set with BEX4 as the core was screened to construct a Nomogram model. BEX4, calmodulin regulated spectrin associated protein 2 (CAMSAP2), and myristoylated alanine rich protein kinase C substrate (MARCKS) were identified as aneuploidy characteristic hub genes. Molecular subtypes in thymoma (THYM), thyroid carcinoma (THCA), and kidney chromophobe (KICH) showed significant differences in tumor cell stemness among different subtypes. The competitive endogenous RNA (ceRNA)-Genes network revealed that hub genes, co-regulated by hsa-miR-425-5p, hsa-miR-200c-3p, and others, regulate microtubules, centrosomes, and microtubule cytoskeleton. Furthermore, elevated BEX4 emerged as a significant protective factor in Pancreatic adenocarcinoma (PAAD), KICH, kidney renal papillary cell carcinoma (KIRP), and kidney renal clear cell carcinoma (KIRC). BEX4, CAMSAP2, and MARCKS specifically express in microtubules, centrioles, and cytoskeletons, influencing tumor chromosome division and inducing aneuploidy. Additionally, the relationship between the acquisition of tumor cell stemness and the severity of aneuploidy varies significantly across tumor types, displaying positive and negative correlations.

Oxidative/Nitrosative Stress and Brain Involvement in Sepsis: A Relationship Supported by Immunohistochemistry.

Background and Objectives: A large amount of recent evidence suggests that cellular inability to consume oxygen could play a notable part in promoting sepsis as a consequence of mitochondrial dysfunction and oxidative stress. The latter could, in fact, represent a fundamental stage in the evolution of the "natural history" of sepsis. Following a study previously conducted by the same working group on heart samples, the present research project aims to evaluate, through an immunohistochemical study, the existence and/or extent of oxidative stress in the brains of subjects who died due to sepsis and define, after reviewing the literature, its contribution to the septic process to support the use of medications aimed at correcting redox anomalies in the management of septic patients. Materials and Methods: 10 cases of subjects who died in healthcare facilities with ante-mortem clinical-laboratory signs that allowed the diagnosis of septic shock were selected as case studies, and 1 case of a subject who died immediately following a road traffic accident was used as a negative control. Samples of the cerebral cortex were then taken, fixed in formalin, and subjected to sections on which an immunohistochemical study was performed using anti-NOX-2, NT, iNOS, and 8-OHdG antibodies. Results: The results emerging from the present study demonstrate that despite a variable expressivity for the NT, iNOS, and NOX2 markers, the brain samples demonstrated univocal and high positivity for the 8-OHdG marker. Conclusions: This would allow us to hypothesize how, regardless of the mechanism of production of ROS and NOS (iNOS or NOX2 mediated) and the pathophysiological mechanisms that are triggered during sepsis, oxidative damage to DNA represents the event to which this whole process leads and, in fact, in the literature, is directly correlated to sepsis-dependent mortality. Neurons, conversely, appear to be more sensitive to oxidative stress because of a low number of protective or scavenger molecules (catalase, glutathione peroxidase, GSH, or vitamin E). Therefore, despite reduced production, the manifestation of the damage remains high. This evidence, together with that of the previous study, can only support the introduction of substances with an antioxidant function in the guidelines for the treatment of sepsis.

Validation of the lung immune prognostic index in patients with untreated advanced non-small cell lung cancer: Post hoc analysis of the impower 130, 131 and 150 trials

IntroductionLIPI has been strongly correlated with immunotherapy (IT) outcomes in advanced NSCLC. Limited data is available for upfront chemotherapy (CT) + IT combinations. We aimed to study its prognostic value in 1st-line CT +/- IT +/- antiangiogenics. MethodsData from patients with wild-type EGFR/ALK aNSCLC included in IMpower150, IMpower131, and IMpower130 (international phase 3 multicenter studies) treated with 1st-line CT +/- atezolizumab and/or bevacizumab were retrospectively analysed. LIPI was calculated based on the neutrophil/(leucocytes-neutrophils) (dNLR) ratio and serum LDH: good (dNLR < 3 and LDH < ULN), intermediate (dNLR ≥ 3 or LDH ≥ ULN) and poor (dNLR ≥ 3 and LDH ≥ ULN). ResultsOut of 2540 patients, 48.6 % were LIPI good, 40.8 % intermediate and 10.6 % poor. LIPI was significantly associated with treatment outcomes (PFS, OS) in the overall cohort (p < 0.001) and in each treatment cohort (all p < 0.001). After adjustment for age, smoking status, number of metastatic sites, brain or liver involvement and performance status, LIPI remained an independent prognostic factor for PFS and OS. In the LIPI good group (n = 1235), longer PFS was observed in patients treated with CT + IT + AA (median [m] PFS 11.27 vs. < 7.6 months with other regimens, p < 0.001), with a trend for OS (mOS 26.1 vs 20.7 months, p = 0.08). No regimen demonstrated significant PFS benefit in the LIPI poor group compared to chemotherapy. LIPI-good + PD-L1 ≥ 50 % (n = 105)showed long responses (mPFS of 11.1 months,mOS not reached). ConclusionsLIPI was prognostic for PFS and OS in prospective trials in aNSCLC, regardless of the treatment regimen. LIPI poor patients derived no benefit from combination treatment. LIPI combined to PD-L1 may improve the upfront treatment selection.

Pathogenic PDE12 variants impair mitochondrial RNA processing causing neonatal mitochondrial disease

Pathogenic variants in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial function. Within this group, an increasing number of families have been identified, where Mendelian genetic disorders implicate defective mitochondrial RNA biology. The PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Here, we report that disease-causing PDE12 variants in three unrelated families are associated with mitochondrial respiratory chain deficiencies and wide-ranging clinical presentations in utero and within the neonatal period, with muscle and brain involvement leading to marked cytochrome c oxidase (COX) deficiency in muscle and severe lactic acidosis. Whole exome sequencing of affected probands revealed novel, segregating bi-allelic missense PDE12 variants affecting conserved residues. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq) revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein. Our data suggest that PDE12 regulates mitochondrial RNA processing and its loss results in neurological and muscular phenotypes.

Brain morphometry in hepatic Wilson disease patients.

Wilson disease (WD) primarily presents with hepatic and neurological symptoms. While hepatic symptoms typically precede the neurological manifestations, copper accumulates in the brain already in this patient group and leads to subclinical brain MRI abnormalities including T2 hyperintensities and atrophy. This study aimed to assess brain morphological changes in mild hepatic WD. WD patients without a history of neurologic symptoms and decompensated cirrhosis and control participants underwent brain MRI at 3T scanner including high-resolution T1-weighted images. A volumetric evaluation was conducted on the following brain regions: nucleus accumbens, caudate, pallidum, putamen, thalamus, amygdala, hippocampus, midbrain, pons, cerebellar gray matter, white matter (WM), and superior peduncle, using Freesurfer v7 software. Whole-brain analyses using voxel- and surface-based morphometry were performed using SPM12. Statistical comparisons utilized a general linear model adjusted for total intracranial volume, age, and sex. Twenty-six WD patients with mild hepatic form (30 ± 9 years [mean age ± SD]); 11 women; mean treatment duration 13 ± 12 (range 0-42) years and 28 healthy controls (33 ± 9 years; 15 women) were evaluated. Volumetric analysis revealed a significantly smaller pons volume and a trend for smaller midbrain and cerebellar WM in WD patients compared to controls. Whole-brain analysis revealed regions of reduced volume in the pons, cerebellar, and lobar WM in the WD group. No significant differences in gray matter density or cortical thickness were found. Myelin or WM in general seems vulnerable to low-level copper toxicity, with WM volume loss showing promise as a marker for assessing brain involvement in early WD stages.

Balancing brain metabolic states during sickness and recovery sleep.

Sickness sleep and rebound following sleep deprivation share humoral signals including the rise of cytokines, in particular interleukins. Nevertheless, they represent unique physiological states with unique brain firing patterns and involvement of specific circuitry. Here, we performed untargeted metabolomics of mouse cortex and hippocampus to uncover changes with sickness and rebound sleep as compared with normal daily sleep. We found that the three settings are biochemically unique with larger differences in the cortex than in the hippocampus. Both sickness and rebound sleep shared an increase in tryptophan. Surprisingly, these two sleep conditions showed opposite modulation of the methionine-homocysteine cycle and differences in terms of the energetic signature, with sickness impinging on glycolysis intermediates whilst rebound increased the triphosphorylated form of nucleotides. These findings indicate that rebound following sleep deprivation stimulates an energy rich setting in the brain that is devoid during sickness sleep.

A Review of Sturge-Weber Syndrome Brain Involvement, Cannabidiol Treatment and Molecular Pathways.

Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder typically caused by a somatic mosaic mutation in R183Q GNAQ. At-risk children present at birth with a capillary malformation port-wine birthmark. The primary diagnostic characteristic of the disorder includes leptomeningeal enhancement of the brain, which demonstrates abnormal blood vessels and results in impaired venous drainage and impaired local cerebral perfusion. Impaired cerebral blood flow is complicated by seizures resulting in strokes, hemiparesis and visual field deficits, hormonal deficiencies, behavioral impairments, and intellectual disability. Therefore, anti-seizure medication in combination with low-dose aspirin is a common therapeutic treatment strategy. Recently published data indicate that the underlying mutation in endothelial cells results in the hyperactivation of downstream pathways and impairment of the blood-brain barrier. Cannabidiol (CBD) has been used to treat medically refractory seizures in SWS due to its anti-seizure, anti-inflammatory, and neuroprotective properties. Pilot research suggests that CBD improves cognitive impairment, emotional regulation, and quality of life in patients with SWS. Recent preclinical studies also suggest overlapping molecular pathways in SWS and in CBD, suggesting that CBD may be uniquely effective for SWS brain involvement. This review aims to summarize early data on CBD's efficacy for preventing and treating epilepsy and neuro-cognitive impairments in patients with SWS, likely molecular pathways impacted, and provide insights for future translational research to improve clinical treatment for patients with SWS.

Neuropsychiatric Manifestations of COVID-19 Disease and Post Covid Syndrome: The Role of N Acetyl-cysteine and Acetyl-L-carnitine.

COVID-19 is associated with neuropsychiatric symptoms, such as anosmia, anxiety, depression, stress-related reactions, and psychoses. The illness can cause persistent cognitive impairment and "brain fog", suggesting chronic brain involvement. Clinical entities of ongoing symptomatic COVID-19 and Post COVID Syndrome (PCS) mainly present neuropsychiatric symptoms such as dysgeusia, headache, fatigue, anxiety, depression, sleep disturbances, and post-traumatic stress disorder. The pathophysiology of COVID-19-related brain damage is unclear, but it is linked to various mechanisms such as inflammation, oxidative stress, immune dysregulation, impaired glutamate homeostasis, glial and glymphatic damage, and hippocampal degeneration. Noteworthy is that the metabotropic receptor mGluR2 was discovered as a mechanism of internalisation of SARS-CoV-2 in Central Nervous System (CNS) cells. N-acetylcysteine (NAC) and acetyl-L-carnitine (ALC) are two supplements that have already been found effective in treating psychiatric conditions. Furthermore, NAC showed evidence in relieving cognitive symptomatology in PCS, and ALC was found effective in treating depressive symptomatology of PCS. The overlapping effects on the glutamatergic system of ALC and NAC could help treat COVID-19 psychiatric symptoms and PCS, acting through different mechanisms on the xc-mGluR2 network, with potentially synergistic effects on chronic pain and neuro-astrocyte protection. This paper aims to summarise the current evidence on the potential therapeutic role of NAC and ALC, providing an overview of the underlying molecular mechanisms and pathophysiology. It proposes a pathophysiological model explaining the effectiveness of NAC and ALC in treating COVID-19-related neuropsychiatric symptoms.

Correlating Thompson score and cardiac dysfunction in neonates suffering from perinatal asphyxia – A prospective observational study

Background: Perinatal asphyxia continues to be a leading cause of neonatal morbidity and mortality worldwide. It causes multiorgan failure with brain involvement as the major organ of concern (hypoxic-ischemic encephalopathy). Cardiac dysfunction is also a feature of perinatal asphyxia. Aims and Objectives: The study and to correlate cardiac dysfunction detected by cardiac biomarkers and echocardiography with the severity of perinatal asphyxia as graded by the Thompson score. Materials and Methods: In this prospective observational study, babies with Apgar score &lt;7 at 1 min received in the sick newborn care unit of a tertiary care hospital in West Bengal, India, were enrolled over 6 months. Thompson’s score was assessed on the 1st day with the estimation of creatine phosphokinase MB (CPK-MB) and troponin (Trn) T within 24 h of birth. Thompson score assessment was continued twice daily till discharge or death. Transthoracic echocardiography was done at the earliest within the 1st week. Results: Of the 81 neonates enrolled, 28 neonates had cardiac dysfunction detected by positive Trn T and raised CPK-MB. Echocardiography showed 15 neonates (18.5%) had systolic dysfunction whereas 13 (16.0%) had tricuspid regurgitation. There was a strong association between Thompson score and Trn T and CPK-MB (rpb=0.85, rho=0.97, respectively, P≤0.001). Thompson score was highly sensitive and specific in detecting the need for mechanical ventilation, and fluid restriction in inotrope-resistant cardiac dysfunction (sensitivity 90%, 78.4%, respectively; and specificity 95.8%, 97.7%, respectively), in predicting initiation of feeding and final outcome (sensitivity 82.9% and 100%, respectively, specificity 97.8%, 89%, respectively). Conclusion: Clinical assessment by the Thompson score can predict the degree of cardiac dysfunction, mechanical ventilation requirement, feed initiation, and final outcome in perinatal asphyxia.

Unusual late presentation of cryptococcal meningitis with simultaneous CMV antigenemia in a kidney transplant recipient.

Cryptococcosis is the third most common invasive fungal infection in solid-organ transplant (SOT) recipients after candidiasis and aspergillosis. These patients are at risk of disseminated cryptococcosis because of immuosuppressive therapy. The median time to disease onset after kidney transplantation is approximately 35months and it rarely occurs more than 10years after transplantation. Herein, we report a case of 64-year-old kidney transplant recipient suffering from coexisting disseminated cryptococcosis with brain and skin involvement, together with cytomegalovirus (CMV) antigenemia more than 20years after transplant. She presented with frontal headache and bilateral hand tremor, in addition to multiple nodular lesions over bilateral lower limbs. The diagnosis was made after lumbar puncture and skin biopsy. She was successfully treated with a course of anti-fungal and anti-CMV regimen without any relapse of central nervous system infection. Our case illustrates that disseminated cryptococcosis can occur very late after organ transplant. It is thus important to watch out for late-onset opportunistic infections and strike the balance between risks of infections and rejections in SOT patients.

Empagliflozin ameliorates olfactory bulbectomy-induced depression by mitigating oxidative stress and possible involvement of brain derived neurotrophic factor in diabetic rats

Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has recently reported to prevent the depression as chronic animal model. However, its impact on neuroinflammation-mediated depression were remains unexplored. The present study aimed to explore the antidepressant potential of empagliflozin using a neuroinflammation-mediated depression involving the olfactory bulbectomy (OBX) model in rats. To establish this model, initially a low dose of streptozotocin was injected to induce diabetes in all group of animals. Following the confirmation of hyperglycemia, OBX surgery was performed. Post-surgery, the drug treatments were administered orally for 14 consecutive days. The study evaluated the effects of daily oral administration of empagliflozin at doses of 5 and 10 mg/kg, alongside metformin (200 mg/kg) and clomipramine (50 mg/kg), on OBX-induced behavioral depression in rats. Separate sham and vehicle control groups were also maintained. Behavioral parameters in open field, forced swim test, elevated plus maze and splash test were recorded on 28th day. Results showed that empagliflozin, particularly at the higher at the higher dose, significantly enhanced behavioral outcomes, evidenced by increased distance traveled, greater open arm entries, and reduced immobility, alongside a notable reduction in grooming time. Moreover, empagliflozin significantly restored the antioxidants level specifically Glutathione (GSH) and Catalase (CAT) in OBX insulted rat brain and reversed Lipid peroxidase (LPO). Notably, molecular docking study demonstrated a good binding affinity of empagliflozin for Brain-Derived Neurotrophic Factor (BDNF), suggesting that its antidepressant effects may be mediated through the modulation of the BDNF pathway. These findings support the potential therapeutic application of empagliflozin for depression, particularly in cases associated with neuroinflammation and oxidative stress.