Neonatal Encephalopathy is a Complex Phenotype Representing Reproductive and Pregnancy Exposome Effects on the Maternal-Placental-Fetal Triad.

Reproductive, pregnancy, and placental exposomes influence the fetal neural exposome through toxic stressor interplay, impairing the maternal-placental-fetal (MPF) triad. Neonatal encephalopathy represents different clinical presentations based on complex time-dependent etiopathogenetic mechanisms including hypoxia-ischemia that challenge diagnosis and prognosis. Reproductive, pregnancy, and placental exposomes impair the fetal neural exposome through toxic stressor interplay within the MPF triad. Long intervals often separate disease onset from phenotype. Interdisciplinary fetal-neonatal neurology training, practice, and research closes this knowledge gap. Maintaining reproductive health preserves MPF triad health with life-course benefits.

Comparison of clinicopathological features between cerebral cystic and alveolar echinococcosis: analysis of 27 cerebral echinococcosis cases in Xinjiang, China.

BACKGROUND: Cerebral echinococcosis is relatively rare, and it is important to distinguish cerebral cystic echinococcosis (CCE) from cerebral alveolar echinococcosis (CAE) in terms of pathological diagnosis. We aim to describe the different clinicopathological features among patients with CCE and CAE. METHODS: We collected 27 cases of cerebral echinococcosis which were diagnosed in the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University from January 1, 2012, to June 30, 2023. We compared the patients' clinical characteristics, MRI features, and pathologic manifestations of CCE and CAE. RESULTS: Among 27 cases of cerebral echinococcosis, 23 cases were CAE and 4 cases were CCE. The clinical manifestations of both CCE and CAE patients mainly included headache (21 patients, 77.78%), limb movement disorders (6 patients, 22.22%), epileptic seizures (4 patients, 14.81%) and visual disturbances (2 patients, 7.41%). The average onset age of CAE cases was 34.96 ± 11.11 years, which was 9.00 ± 7.26 years in CCE cases. All CAE patients presented with multiple involvements in the brain and extracranial organs while all CCE patients observed a solitary lesion in the brain and 3 CCE cases had no extracranial involvement. Lesions of CCE in MRI showed a single isolated circular, which was well demarcated from the surrounding tissues and with no obvious edema around the lesions, whereas CAE lesions presented as multiple intracranial lesions, with blurred edges and edema around the lesions, and multiple small vesicles could be observed in the lesions. The edge of CAE lesions could be enhanced, while CCE lesions have no obvious enhancement. CCE foci were clear cysts with a wall of about 0.1 cm. Microscopically, the walls of the cysts were characterized by an eosinophilic keratin layer, which was flanked on one side by basophilic germinal lamina cells, which were sometimes visible as protocephalic nodes. While the CAE lesion was a nodular structure with a rough and uneven nodule surface, and the cut section was cystic and solid; microscopically, the CAE lesion had areas of coagulative necrosis, and the proto-cephalic nodes were barely visible. Inflammatory cell areas consisting of macrophages, lymphocytes, epithelioid cells, plasma cells, eosinophils, and fibroblasts can be seen around the lesion. Brain tissues in the vicinity of the inflammatory cell areas may show apoptosis, degeneration, necrosis, and cellular edema, while brain tissues a little farther away from the lesion show a normal morphology. CONCLUSIONS: With the low incidence of brain echinococcosis, the diagnosis of echinococcosis and the differential diagnosis of CAE and CCE are challenging for pathologists. Grasping the different clinical pathology characteristics of CAE and CCE is helpful for pathologists to make accurate diagnoses.

Single-centre real-life observational study on mortality and outcomes: decompressive craniectomy and brain death in traumatic brain injury, haemorrhage, and other cerebral diseases.

BACKGROUND: Decompressive hemicraniectomy (DHC) is used after severe brain damages with elevated, refractory intracranial pressure (ICP). In a non age-restricted population, mortality rates and long-term outcomes following DHC are still unclear. This study's objectives were to examine both, as well as to identify predictors of unfavourable outcomes. METHODS: We undertook a retrospective observational analysis of patients aged 18 years and older who underwent DHC at the University Hospital of Bonn between 2018 and 2020, due to traumatic brain injury (TBI), haemorrhage, tumours or infections. Patient outcomes were assessed by conducting telephone interviews, utilising questionnaires for modified Rankin Scale (mRS) and extended Glasgow Outcome scale (GOSE). We evaluated the health-related quality of life using the EuroQol (EQ-5D-5L) scale. RESULTS: A total of 144 patients with a median age of 58.5 years (range: 18 to 85 years) were evaluated. The mortality rate was 67%, with patients passing away at a median of 6.0 days (IQR [1.9-37.6]) after DHC. Favourable outcomes, as assessed by the mRS and GOSE were observed in 10.4% and 6.3% of patients, respectively. Cox regression analysis revealed a 2.0% increase in the mortality risk for every year of age (HR = 1.017; 95% CI [1.01-1.03]; p = 0.004). Uni- and bilateral fixed pupils were associated with a 1.72 (95% CI [1.03-2.87]; p = 0.037) and 3.97 (95% CI [2.44-6.46]; p < 0.001) times higher mortality risk, respectively. ROC-analysis demonstrated that age and pupillary reactivity predicted 6-month mortality with an AUC of 0.77 (95% CI [0.69-0.84]). The only parameter significantly associated with a better quality of life was younger age. CONCLUSIONS: Following DHC, mortality remains substantial, and favourable outcomes occur rarely. Particularly in elderly patients and in the presence of clinical signs of herniation, mortality rates are notably elevated. Hence, the indication for DHC should be set critically.

Pediatric Cranial Ultrasound Revisited: A Comprehensive Review.

ABSTRACT: Cranial ultrasound (CUS) is an indispensable tool in the evaluation of intracranial pathology in premature and term neonates and older infants. Familiarity with standard cranial ultrasound techniques and parameters, normal anatomy, and commonly encountered abnormalities is crucial for providing appropriate care for these patients. This review provides a comprehensive overview of cranial ultrasound in clinical practice.

[Thinking on the classification of non-invasive brain stimulation as neuromodulation technique].

Neuromodulation techniques have gradually evolved from electrical or chemical methods to various physical stimulation techniques including electricity, magnetism, sound, light, heat, and more. However, the clinical efficacy and mechanisms of each stimulation technique or paradigm vary greatly. To facilitate the understanding of the therapeutic effects and mechanisms of different neuromodulation techniques, combined with current clinical practice, the author takes the classification of non-invasive transcranial electrical stimulation as an example and proposes the idea of using energy magnitude as the primary classification and different media/stimulation routes as the secondary classification. This classification emphasizes the energy essence of various physical stimuli, followed by the transmission carriers of physical stimuli. This classification method helps to guide and design neuromodulation paradigms for different target symptoms in various brain disorders, which is beneficial for better serving clinical diagnosis and treatment. The Expert Forum also discusses the advantages and disadvantages of various neuromodulation technologies and their clinical applications.

Difficulties in the Diagnostics and Treatment of Hashimoto's Encephalopathy-A Systematic and Critical Review.

Hashimoto's encephalopathy (HE) has been a poorly understood disease. It has been described in all age group, yet, there is no specific HE marker. Additionally, the treatment data in the available studies are frequently divergent and contradictory. Therefore, the aim of our systematic and critical review is to evaluate the diagnosis and treatment of HE in view of the latest findings. The databases browsed comprised PubMed, Scopus, and Google Scholar as well as Cochrane Library, and the search strategy included controlled vocabulary and keywords. A total of 2443 manuscripts were found, published since the beginning of HE research until February 2024. In order to determine validity of the data collected from studies, bias assessment was performed using RoB 2 tool. Ultimately, six studies were included in our study. HE should be considered in the differential diagnosis in patients with psychiatric and neurological symptoms. According to our findings, negative thyroid peroxidase antibodies (anti-TPOs) may represent a valuable parameter in ruling out HE. Nonetheless, this result cannot be used to confirm HE. Furthermore, the proposed anti NH2-terminal-α-enolase (anti-NAE) is non-specific for HE. The effectiveness of glucocorticoid therapy is 60.94%, although relapse occurs in 31.67% of patients following the treatment. Our review emphasizes the significance of conducting further large-scale research and the need to take into account the potential genetic factor.

De Novo DNM1L Mutation in a Patient with Encephalopathy, Cardiomyopathy and Fatal Non-Epileptic Paroxysmal Refractory Vomiting.

Mitochondrial fission and fusion are vital dynamic processes for mitochondrial quality control and for the maintenance of cellular respiration; they also play an important role in the formation and maintenance of cells with high energy demand including cardiomyocytes and neurons. The DNM1L (dynamin-1 like) gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family that is responsible for the fission of mitochondria; it is ubiquitous but highly expressed in the developing neonatal heart. De novo heterozygous pathogenic variants in the DNM1L gene have been previously reported to be associated with neonatal or infantile-onset encephalopathy characterized by hypotonia, developmental delay and refractory epilepsy. However, cardiac involvement has been previously reported only in one case. Next-Generation Sequencing (NGS) was used to genetically assess a baby girl characterized by developmental delay with spastic-dystonic, tetraparesis and hypertrophic cardiomyopathy of the left ventricle. Histochemical analysis and spectrophotometric determination of electron transport chain were performed to characterize the muscle biopsy; moreover, the morphology of mitochondria and peroxisomes was evaluated in cultured fibroblasts as well. Herein, we expand the phenotype of DNM1L-related disorder, describing the case of a girl with a heterozygous mutation in DNM1L and affected by progressive infantile encephalopathy, with cardiomyopathy and fatal paroxysmal vomiting correlated with bulbar transitory abnormal T2 hyperintensities and diffusion-weighted imaging (DWI) restriction areas, but without epilepsy. In patients with DNM1L mutations, careful evaluation for cardiac involvement is recommended.

Small Scale, Big Impact: Nanotechnology-Enhanced Drug Delivery for Brain Diseases.

Central nervous system (CNS) diseases, ranging from brain cancers to neurodegenerative disorders like dementia and acute conditions such as strokes, have been heavily burdening healthcare and have a direct impact on patient quality of life. A significant hurdle in developing effective treatments is the presence of the blood-brain barrier (BBB), a highly selective barrier that prevents most drugs from reaching the brain. The tight junctions and adherens junctions between the endothelial cells and various receptors expressed on the cells make the BBB form a nonfenestrated and highly selective structure that is crucial for brain homeostasis but complicates drug delivery. Nanotechnology offers a novel pathway to circumvent this barrier, with nanoparticles engineered to ferry drugs across the BBB, protect drugs from degradation, and deliver medications to the designated area. After years of development, nanoparticle optimization, including sizes, shapes, surface modifications, and targeting ligands, can enable nanomaterials tailored to specific brain drug delivery settings. Moreover, smart nano drug delivery systems can respond to endogenous and exogenous stimuli that control subsequent drug release. Here, we address the importance of the BBB in brain disease treatment, summarize different delivery routes for brain drug delivery, discuss the cutting-edge nanotechnology-based strategies for brain drug delivery, and further offer valuable insights into how these innovations in nanoparticle technology could revolutionize the treatment of CNS diseases, presenting a promising avenue for noninvasive, targeted therapeutic interventions.

Edaravone combined with hyperbaric oxygen therapy in delayed encephalopathy after acute carbon monoxide poisoning: A meta-analysis.

BACKGROUND: The use of both edaravone (EDA) and hyperbaric oxygen therapy (HBOT) is increasingly prevalent in the treatment of delayed encephalopathy after carbon monoxide poisoning (DEACMP). This meta-analysis aims to evaluate the efficacy of using EDA and HBOT in combination with HBOT alone in the treatment of DEACMP. METHODS: We searched and included all randomized controlled trials (RCTs) published before November 6, 2023, from 12 Chinese and English databases and clinical trial centers in China and the United States. The main outcome indicator was the total effective rate. The secondary outcome indicators included the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), Hasegawa Dementia Scale (HDS), Fugl-Meyer Assessment (FMA), Superoxide Dismutase (SOD), and Malondialdehyde (MDA). Statistical measures utilized include risk ratios (RR), weighted mean difference (WMD), and 95 % confidence intervals (95 % CI). RESULTS: Thirty studies involving a combined total of 2075 participants were ultimately incorporated. It was observed that the combination of EDA with HBOT for the treatment of DEACMP demonstrated an improvement in the total effective rate (RR: 1.25; 95 % CI: 1.20-1.31; P < 0.01), MMSE (WMD: 3.67; 95 % CI: 2.59-4.76; P < 0.01), MoCA (WMD: 4.38; 95 % CI: 4.00-4.76; P < 0.01), BI (WMD: 10.94; 95 % CI: 5.23-16.66; P < 0.01), HDS (WMD: 6.80; 95 % CI: 4.05-9.55; P < 0.01), FMA (WMD: 8.91; 95 % CI: 7.22-10.60; P < 0.01), SOD (WMD: 18.45; 95 % CI: 16.93-19.98; P < 0.01); and a reduction in NIHSS (WMD: -4.12; 95 % CI: -4.93 to -3.30; P < 0.01) and MDA (WMD: -3.05; 95 % CI: -3.43 to -2.68; P < 0.01). CONCLUSION: Low-quality evidence suggests that for DEACMP, compared to using HBOT alone, the combined use of EDA and HBOT may be associated with better cognition and activity of daily living. In the future, conducting more meticulously designed multicenter and large-sample RCTs to substantiate our conclusions is essential.

Clinical characteristics and prognosis of paediatric respiratory syncytial virus-related encephalopathy.

BACKGROUND: To understand the clinical characteristics and prognosis of respiratory syncytial virus (RSV)-related encephalopathy in children. METHODS: A retrospective analysis of the data of children who were diagnosed with RSV-related encephalopathy and admitted to the paediatric intensive care unit (PICU) of Beijing Children's Hospital between November 2016 and November 2023 was performed. RESULTS: Four hundred and sixty-four children with RSV infection were treated in the PICU, and eight of these patients (1.7%) were diagnosed with RSV-related encephalopathy. The mean age of the patients was 24.89 (5.92 ∼ 36.86) months. Two patients had underlying diseases. The time from the onset of illness to impaired consciousness was 3 (1.88-3.75) days. Five patients had convulsions, and three patients had an epileptic status. The serum procalcitonin (PCT) level was 1.63 (0.24, 39.85) ng/ml for the eight patients, and the cerebrospinal fluid (CSF) protein level was 232 (163 ∼ 848) g/L. Among the 8 patients, four patients underwent electroencephalogram (EEG) monitoring or examination. One patient showed continuous low-voltage, nonresponsive activity, and another patient displayed persistent slow waves, the remaining two patients had negative results. One patient had a combination of acute necrotizing encephalopathy (ANE) and acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Additionally, one patient had ANE, and another had acute brain swelling (ABS). One patient died in the hospital, and the other seven patients were discharged with improvement. Routine follow-up was conducted for 4.58(0.5 ∼ 6.50) years, and all patients fully recovered. CONCLUSIONS: RSV-related encephalopathy could have varying clinical manifestations, and some types, such as ANE and ABS, are dangerous and can lead to death.

Adaptive node feature extraction in graph-based neural networks for brain diseases diagnosis using self-supervised learning.

Electroencephalography (EEG) has demonstrated significant value in diagnosing brain diseases. In particular, brain networks have gained prominence as they offer additional valuable insights by establishing connections between EEG signal channels. While brain connections are typically delineated by channel signal similarity, there lacks a consistent and reliable strategy for ascertaining node characteristics. Conventional node features such as temporal and frequency domain properties of EEG signals prove inadequate for capturing the extensive EEG information. In our investigation, we introduce a novel adaptive method for extracting node features from EEG signals utilizing a distinctive task-induced self-supervised learning technique. By amalgamating these extracted node features with fundamental edge features constructed using Pearson correlation coefficients, we showed that the proposed approach can function as a plug-in module that can be integrated to many common GNN networks (e.g., GCN, GraphSAGE, GAT) as a replacement of node feature selections module. Comprehensive experiments are then conducted to demonstrate the consistently superior performance and high generality of the proposed method over other feature selection methods in various of brain disorder prediction tasks, such as depression, schizophrenia, and Parkinson's disease. Furthermore, compared to other node features, our approach unveils profound spatial patterns through graph pooling and structural learning, shedding light on pivotal brain regions influencing various brain disorder prediction based on derived features.

RNA-Seq analysis of the fruiting bodies and mycelia of angel-wing mushroom Pleurocybella porrigens that cause acute encephalopathy.

OBJECTIVE: In 2004, after consuming angel-wing mushrooms, Pleurocybella porrigens, 59 incidents of food poisoning were reported in Japan. Consequently, 17 individuals died of acute encephalopathy. In 2023, we proved that a lectin, pleurocybelline, and pleurocybellaziridine from this mushroom caused damage to the brains of mice. Although we reported genomic and transcriptomic data of P. porrigens in 2013, the assembly quality of the transcriptomic data was inadequate for accurate functional annotation. Thus, we obtained detailed transcriptomic data on the fruiting bodies and mycelia of this mushroom using Illumina NovaSeq 6000. RESULTS: De novo assembly data indicated that the N50 lengths for the fruiting bodies and mycelia were improved compared with those previously reported. The differential expression analysis between the fruiting bodies and the mycelia revealed that 1,937 and 1,555 genes were significantly up-regulated in the fruiting bodies and the mycelia, respectively. The biological functions of P. porrigens transcripts, including PA biosynthetic pathways, were investigated using BLAST search, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analysis. The obtained results revealed L-valine, a predicted precursor of PA, is biosynthesized in the fruiting bodies and mycelia. Furthermore, real-time RT-PCR was performed to evaluate the accuracy of the results of differential expression analysis.

Cefepime Neurotoxicity in Patients With Normal Renal Function: An Overlooked Cause of Encephalopathy in the Intensive Care Unit.

Cefepime is a fourth-generation cephalosporin with extended antimicrobial coverage. Concerns have been raised about the side effects of cefepime including myoclonus, encephalopathy, and seizures, especially when renal impairment is present. There have been reports of cases of adverse neurological consequences despite appropriate renal adjustment. Here, we present a case of a 69-year-old patient initially diagnosed with pneumonia and treated with cefepime. The patient later developed altered mental status, leading to differential diagnoses including stroke, drug overdose, or non-convulsive seizures. Following a comprehensive workup, it was determined that she had cefepime-induced encephalopathy, despite having normal kidney function, which resolved completely after discontinuing the medication. In addition, we include similar cases retrieved from PubMed up to the present date, to the best of our knowledge.

Incidence of seizures in ICU patients with diffuse encephalopathy and its predictors.

Encephalopathy is a diffuse brain dysfunction that results from systemic disorder. Patients with diffuse encephalopathy are at risk of developing clinical and electrographic seizures. The aim of this study is to assess the prevalence of electrographic seizures in a setting of encephalopathy and the clinical and electroencephalogram predictors. We retrospectively reviewed all continuous electroencephalograms done between 2019 and 2022. Continuous electroencephalograms with diffuse encephalopathy were included in the study. A total of 128 patients with diffuse encephalopathy were included in this study. Patients' ages ranged from 18 to 96 years old with a mean age of 55.3 ±â€…19.2 years old. Nine out of 128 patients had seizures with an incidence of 7%. Sixty-six point six percent were nonconvulsive electrographic seizures. Fourteen point three percent of the female patients with diffuse encephalopathy had seizures as compared to none of the male patients (P = .002). Also, 12% of patients with a history of epilepsy experienced seizures versus 5.8% of patients without this history (P = .049). Among electrographic features, 25% of patients with delta background had seizures versus 2.3% of the other patients (P = .048). Likewise, 90% of patients with periodic discharges developed seizures in comparison with none of the patients without (P = .001). Seizures are seen in 7% of patients with diffuse encephalopathy. Female gender, past history of epilepsy, delta background and periodic discharges are significant predictors of seizure development in patients with diffuse encephalopathy.

A novel splicing mutation DNAH5 c.13,338 + 5G > C is involved in the pathogenesis of primary ciliary dyskinesia in a family with primary familial brain calcification.

BACKGROUND: Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. METHODS: In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. RESULTS: The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. CONCLUSIONS: The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.