Long-term survival of traumatic brain injury and intra-cerebral haemorrhage patients: A multicentric observational cohort.

PURPOSE: Mortality is often assessed during ICU stay and early after, but rarely at later stage. We aimed to compare the long-term mortality between TBI and ICH patients. MATERIALS AND METHODS: From an observational cohort, we studied 580 TBI patients and 435 ICH patients, admitted from January 2013 to February 2021 in 3 ICUs and alive at 7-days post-ICU discharge. We performed a Lasso-penalized Cox survival analysis. RESULTS: We estimated 7-year survival rates at 72.8% (95%CI from 67.3% to 78.7%) for ICH patients and at 84.9% (95%CI from 80.9% to 89.1%) for TBI patients: ICH patients presenting a higher mortality risk than TBI patients. Additionally, we identified variables associated with higher mortality risk (age, ICU length of stay, tracheostomy, low GCS, absence of intracranial pressure monitoring). We also observed anisocoria related with the mortality risk in the early stage after ICU stay. CONCLUSIONS: In this ICU survivor population with a prolonged follow-up, we highlight an acute risk of death after ICU stay, which seems to last longer in ICH patients. Several variables characteristic of disease severity appeared associated with long-term mortality, raising the hypothesis that the most severe patients deserve closer follow-up after ICU stay.

Cerebral haemorrhage in the patient with atrial fibrillation: do we employ the direct oral anticoagulants without waiting too long?

Intracranial haemorrhage (ICH) is the most feared haemorrhagic complication of oral anticoagulant therapy (OAT), although the risk is significantly lower with direct oral anticoagulants (DOACs) compared with warfarin. Intracranial haemorrhage is generally considered, by clinicians, to be an absolute contraindication to starting or resuming OAT in patients with atrial fibrillation (AF). On the other hand, the pivotal trials with DOACs excluded patients with previous ICH. Observational studies actually indicate a net clinical benefit in favour of DOAC in patients with AF and previous ICH. This benefit is confirmed by randomized clinical trials which, however, have the limitation of the small number of cases, but larger clinical trials comparing DOACs vs. aspirin or no therapy are underway. While OAT is certainly contraindicated in patients with lobar ICH and cerebral amyloid angiopathy, in other cases, the decision must be made in the individual patient through an accurate balance between thromboembolic risk and haemorrhagic risk and a multidisciplinary cardio-neurological evaluation.

Early seizures and risk of epilepsy and death after intracerebral haemorrhage: The MUCH Italy.

INTRODUCTION: It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality. PATIENTS AND METHODS: In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014. RESULTS: Among 2570 patients (mean age, 73.4 ± 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26). DISCUSSION AND CONCLUSION: The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures.

Correlation of levels of lactic acid and glucose in cerebrospinal fluid of cerebral hemorrhage patients with the occurrence of postoperative intracranial infection and clinical prognosis.

Background: Cerebral haemorrhage is a critical condition that often requires surgical treatment, and postoperative intracranial infection can significantly impact patient outcomes. The aim of the study was to examine the relationship between the levels of lactic acid and glucose in cerebrospinal fluid (CSF) of patients with cerebral haemorrhage and their postoperative intracranial infection and clinical prognosis. Methods: The study selected the clinical data of 324 patients with cerebral haemorrhage who underwent surgical treatment in our hospital from March 2020 to March 2022 for retrospective analysis and divided these patients into the intracranial infection group (Group A, n=22, leukocyte values in CSF>5×106/L) and the non-intracranial infection group (Group B, n=302, leukocyte values in CSF 5×106/L) according to the occurrence of postoperative intracranial infection in patients to detect the levels of lactic acid and glucose in CSF at different times in the two groups. Pearson method was adopted to analyze the correlation of the levels of lactic acid and glucose in CSF of patients with intracranial infection, and the Glasgow Outcome Scale (GOS) was used to assess the clinical prognosis of patients. According to their scores, these patients were divided into the good prognosis group (GPG, scores of 4-5 points, n=178) and the poor prognosis group (PPG, scores of 1-3 points, n=146). The levels of lactic acid and glucose in the CSF of patients in the two groups were measured, and the Pearson method was adopted to analyze the relationship between these levels and clinical prognosis.

Automated detection of fatal cerebral haemorrhage in postmortem CT data.

During the last years, the detection of different causes of death based on postmortem imaging findings became more and more relevant. Especially postmortem computed tomography (PMCT) as a non-invasive, relatively cheap, and fast technique is progressively used as an important imaging tool for supporting autopsies. Additionally, previous works showed that deep learning applications yielded robust results for in vivo medical imaging interpretation. In this work, we propose a pipeline to identify fatal cerebral haemorrhage on three-dimensional PMCT data. We retrospectively selected 81 PMCT cases from the database of our institute, whereby 36 cases suffered from a fatal cerebral haemorrhage as confirmed by autopsy. The remaining 45 cases were considered as neurologically healthy. Based on these datasets, six machine learning classifiers (k-nearest neighbour, Gaussian naive Bayes, logistic regression, decision tree, linear discriminant analysis, and support vector machine) were executed and two deep learning models, namely a convolutional neural network (CNN) and a densely connected convolutional network (DenseNet), were trained. For all algorithms, 80% of the data was randomly selected for training and 20% for validation purposes and a five-fold cross-validation was executed. The best-performing classification algorithm for fatal cerebral haemorrhage was the artificial neural network CNN, which resulted in an accuracy of 0.94 for all folds. In the future, artificial neural network algorithms may be applied by forensic pathologists as a helpful computer-assisted diagnostics tool supporting PMCT-based evaluation of cause of death.

Diagnostic accuracy of dual-energy computed tomography in the diagnosis of neurological complications after endovascular treatment of acute ischaemic stroke: a systematic review and meta-analysis.

OBJECTIVES: To investigate dual-energy computed tomography's (DECT) diagnostic performance in detecting neurological complications following endovascular therapy (EVT) of acute ischaemic stroke (AIS). METHODS: We performed the literature search using Web of Science, Scopus, PubMed, EBSCO, and Science Direct databases for published related studies. The selected studies estimated the validity of DECT in the detection of neurological complications after EVT for AIS. Study quality assessment was performed utilizing the Quality of Diagnostic Accuracy Studies-2 Tool. Our meta-analysis calculated the pooled sensitivity, negative likelihood ratio, specificity, and positive likelihood ratio for each detected complication. The summary receiver operating characteristics (sROC) curve was utilized to estimate the area under the curve (AUC). RESULTS: Of 22 studies, 21 were included in the quantitative synthesis. In the detection of intracerebral haemorrhage (ICH), DECT pooled overall sensitivity and specificity were 69.9% (95% CI, 44.5%-86.8%) and 100% (95% CI, 92.1%-100%); whereas, in the detection of ischaemia, they were 85.9% (95% CI, 80.4%-90%) and 90.7% (95% CI, 87%-93.5%), respectively. On the sROC curve, AUC values of 0.954 and 0.952 were recorded for the detection of ICH and ischaemia, respectively. CONCLUSIONS: DECT demonstrated high accuracy and specificity in the detection of neurological complications post-endovascular treatment of AIS. However, further prospective studies with a standardized reference test and a larger sample size are recommended to support these findings. ADVANCES IN KNOWLEDGE: DECT is a rapid and valid imaging tool for the prediction of ICH and cerebral ischaemia after the EVT of AIS.

The role of peritoneal dialysis in the treatment of acute kidney injury in neurocritical patients: a retrospective Brazilian study.

BACKGROUND: Acute kidney injury (AKI) occurs frequently in the neurocritical intensive care unit and is associated with greater morbidity and mortality. AKI and its treatment, including acute kidney replacement therapy, can expose patients to a secondary greater brain injury. This study aimed to explore the role of peritoneal dialysis (PD) in neurocritical AKI patients in relation to metabolic and fluid control, complications related to PD and outcome. METHODS: Neurocritical AKI patients were treated by PD (prescribed Kt/V = 0.40/session) using a flexible catheter and a cycler and lactate as a buffer. RESULTS: A total of 58 patients were included. The mean age was 61.8 ± 13.2 years, 65.5% were in the intensive care unit, 68.5% needed intravenous inotropic agents, 72.4% were on mechanical ventilation, APACHE II was 16 ± 6.67 and the main neurological diagnoses were stroke (25.9%) and intracerebral haemorrhage (31%). Ischaemic acute tubular necrosis (iATN) was the most common cause of AKI (51.7%), followed by nephrotoxic ATN AKI (25.8%). The main dialysis indications were uraemia and hypervolemia. Blood urea and creatinine levels stabilised after four sessions at around 48 ± 11 mg/dL and 2.9 ± 0.4 mg/dL, respectively. Negative fluid balance and ultrafiltration increased progressively and stabilised around 2.1 ± 0.4 L /day. Weekly delivered Kt/V was 2.6 ± 0.31. The median number of high-volume PD sessions was 6 (4-10). Peritonitis and mechanical complications were not frequent (8.6% and 10.3%, respectively). Mortality rate was 58.6%. Logistic regression identified as factors associated with death in neurocritical AKI patients: age (odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.09-2.16, p = 0.001), nephrotoxic AKI (OR = 0.78, 95% CI = 0.69- 0.95, p = 0.03), mechanical ventilation (OR = 1.54, 95% CI = 1.17-2.46, p = 0.01), intracerebral haemorrhage as main neurological diagnoses (OR = 1.15, 95% CI = 1.09-2.11, p = 0.03) and negative fluid balance after two PD sessions (OR = 0.94, 95% CI = 0.74-0.97, p = 0.009). CONCLUSION: Our study suggests that careful prescription may contribute to providing adequate treatment for most neurocritical AKI patients without contraindications for PD use, allowing adequate metabolic and fluid control, with no increase in the number of infectious, mechanical and metabolic complications. Mechanical ventilation, positive fluid balance and intracerebral haemorrhage were factors associated with mortality, while patients with nephrotoxic AKI had lower odds of mortality compared to those with septic and ischaemic AKI. Further studies are needed to investigate better the role of PD in neurocritical patients with AKI.

Cycling-related cranio-spinal injuries admitted to a Major Trauma Centre in the cycling capital of the UK.

BACKGROUND: The increased popularity of cycling is leading to an anticipated increase in cycling-related traffic accidents and a need to better understand the demographics and epidemiology of craniospinal injuries in this vulnerable road user group. This study aims to systematically investigate and characterise cycling-related head and spine injuries seen in the Major Trauma Centre for the Eastern region, which has the highest cycling rates in the UK. METHODS: We performed a retrospective cohort study comparing the incidence, patterns, and severity of head and spine injuries in pedal cyclists presenting to the Major Trauma Centre in Cambridge between January 2012 and December 2020. Comparisons of injury patterns, characteristics, and associations were made according to mechanism of injury, helmet use, patient age and gender. RESULTS: A total of 851 patients were admitted after being involved in cycling-related collisions over the study period, with 454 (53%) sustaining head or spine injuries. The majority of victims (80%) were male and in mid-adulthood (median age 46 years). Head injuries were more common than spine injuries, with the most common head injuries being intracranial bleeds (29%), followed by skull fractures (12%), and cerebral contusions (10%). The most common spine injuries were cervical segment fractures, particularly C6 (9%), C7 (9%), and C2 (8%). Motorised collisions had a higher prevalence of spine fractures at each segment (p < 0.001) and were associated with a higher proportion of multi-vertebral fractures (p < 0.001). These collisions were also associated with impaired consciousness at the scene and more severe systemic injuries, including a lower Glasgow coma scale (R = -0.23, p < 0.001), higher injury severity score (R = 0.24, p < 0.001), and longer length of stay (R = 0.21, p < 0.001). Helmet use data showed that lack of head protection was associated with more severe injuries and poorer outcomes. CONCLUSION: As cycling rates continue to increase, healthcare providers may expect to see an increase in bicycle-related injuries in their practice. The insights gained from this study can inform the treatment of these injuries while highlighting the need for future initiatives aimed at increasing road safety and accident prevention.

Study of 851 cycling-related trauma patients in Cambridge, UK, shows high rates of head & spine injuries.Motorised collisions were associated with more severe injuries and impaired consciousness at the scene.The lack of helmet use was linked to more severe head injuries and impaired consciousness, but not to a longer hospital stay.Rising cycling rates may lead to increased incidence of these injuries in clinical practice.Our findings may be relevant for clinicians treating cycling-related traumatic injuries to head and spine.

A Comprehensive Review on Therapeutic Potential of a Natural Anthraquinone Derivative Emodin in Brain-related Disorders.

Brain-related disorders are one of the world's most important and complex health problems today. These brain-related disorders are responsible for a massive number of morbidities and death all around the world. However, researchers have devoted a large amount of time to investigating these diseases and found positive results; nevertheless, there are currently quite a few medications available to treat them. Emodin (EM), a polyphenol compound, has many health benefits. It is a biologically active monomer derived from rhubarb root that exhibits anti-inflammation, anti-oxidation, anticancer, and neuroprotective properties. A series of preclinical trials have shown EM to have protective benefits against many brain-related diseases. This review has evaluated the potential of EM as a pharmacological agent for the treatment and management of various brain-related disorders based on the findings of multiple pre-clinical studies and taking into account the compound's therapeutic properties.

Iatrogenic cerebral amyloid angiopathy: An illustrative case of a newly introduced disease.

BACKGROUND AND PURPOSE: Iatrogenic cerebral amyloid angiopathy (iCAA) is a specific type of cerebral amyloid angiopathy which is becoming increasingly diagnosed. It has been hypothesized that iCAA might arise as a late consequence of past neurosurgical interventions involving dural patch grafts. Positron emission tomography (PET) scans with amyloid tracers and the assay of beta-amyloid levels in cerebrospinal fluid (CSF) are auxiliary criteria, however, definite diagnosis remains histopathologically determined. METHODS: Case report. RESULTS: We present a 48-year-old patient who suffered multiple lobar cerebral haemorrhages from the age of 47. The patient had undergone surgery for remolval of hemangioblastoma with lyophilized dural graft at the age of 11, in 1987. Brain MRI, amiloid PET and CSF analysis led to a diagnosis of probable iCAA. CONCLUSION: It is necessary to increase the awareness of iCAA, in order to avoid overlooking the potential causal involvement of surgical procedures which took place far back in time. Moreover, the diagnostic relevance of amyloid PET and beta-amyloid levels in CSF must be emphasised.

Economic Evaluation of Clinical, Nutritional and Rehabilitation Interventions on Oropharyngeal Dysphagia after Stroke: A Systematic Review.

BACKGROUND: Post-stroke oropharyngeal dysphagia (PS-OD) and its complications increase healthcare costs, suggesting that its appropriate management is cost-effective. We aimed to assess the efficiency of healthcare interventions in PS-OD management. METHODS: A systematic review was conducted following PRISMA recommendations. Four databases were searched from inception through 30 June 2021. Outcome measures were cost-effectiveness and cost-savings of healthcare interventions. English and Spanish literature were included. Narrative and tables were used to present and synthesise evidence. Quality was evaluated using the CHEERS Statement. RESULTS: A total of 244 studies were identified, and 10 were included. Screening and diagnosis of PS-OD studies found: (1) adjusted reduction in hospitalisation costs when assessed during the first admission day; (2) non-significant reduction in hospitalisation costs with OD management after thrombolysis; and (3) videofluoroscopy as the most cost-effective screening method (compared to bedside evaluation and a combination of both). Two studies showed cost-effective rehabilitation programmes, including OD management. Pelczarska et al. showed an incremental cost-utility ratio of texture-modified diets using a gum-based thickener of 20,977 PLN (4660€) following a dynamic model, and Kotecki et al. commercially prepared thickened fluids that were 44% to 59% less expensive than in situ prepared fluids. Elia et al. showed home enteral nutrition was cost-effective (£12,817/QALY), and Beavan et al. showed higher nutrient intake and low increase in hospitalisation costs using looped-nasogastric tubes (£5.20 for every 1% increase). Heterogeneity between studies precluded a quantitative synthesis. CONCLUSIONS: Included studies suggest that healthcare interventions aiming to prevent OD complications are cost-effective. However, studies assessing novel strategies are needed.

Outcomes after inter-hospital transfer of intensive care patients with haemorrhagic stroke: a 5-year retrospective review.

BACKGROUND: Inter-hospital transfer (IHT) of intensive care patients is a limited resource. We assessed the outcomes of patients with haemorrhagic stroke requiring IHT and intensive care and aimed to identify early prognostic factors of poor neurological outcome. METHODS: We conducted a retrospective observational cohort study of patients admitted to a single tertiary intensive care unit (ICU) with haemorrhagic stroke after IHT between January 2014 and December 2018. Primary outcome was poor neurological outcome (modified Rankin Scale ≥4 at time of discharge from hospital or rehabilitation unit). Secondary outcomes were mortality rate, rate of intervention, rate of organ donation surgery (ODS) and potentially avoidable transfer (PAT). PAT was defined as transfer where the patient did not receive an intervention and had a poor neurological outcome. RESULTS: Ninety patients were included in this study, 48 with intracerebral haemorrhage (ICH) and 42 with subarachnoid haemorrhage (SAH). Fifty-one (56.7%) patients had a poor neurological outcome, including 30 (33%) who died. Factors significantly associated with poor neurological outcome included age > 80 years, lower presenting Glasgow Coma Score (GCS) and bilaterally fixed and dilated pupils. Stepwise logistic regression demonstrated history of hypertension as significantly associated with poor neurological outcome in patients with ICH (P = 0.021). Seven (7.8%) patients had ODS. Sixty-four (71.1%) patients received intervention and 20 (22.2%) transfers were potentially avoidable. CONCLUSIONS: Patients in this cohort are at high risk of poor neurological outcome. Prognostic factors identified in this study may help referring, retrieval and receiving clinicians to discuss futility prior to pursuing IHT.

Development and validation of a novel radiomics-clinical model for predicting post-stroke epilepsy after first-ever intracerebral haemorrhage.

OBJECTIVES: Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. This study aimed to develop and validate a novel prediction model combining clinical factors and radiomics features to accurately identify patients at high risk of developing PSE after intracerebral haemorrhage (ICH). METHODS: Researchers performed a retrospective medical chart review to extract derivation and validation cohorts of patients with first-ever ICH that attended two tertiary hospitals in China between 2010 and 2020. Clinical data were extracted from electronic medical records and supplemented by tele-interview. Predictive clinical variables were selected by multivariable logistic regression to build the clinical model. Predictive radiomics features were identified, and a Rad-score was calculated according to the coefficient of the selected feature. Both clinical variables and radiomic features were combined to build the radiomics-clinical model. Performances of the clinical, Rad-score, and combined models were compared. RESULTS: A total of 1571 patients were included in the analysis. Cortical involvement, early seizures within 7 days of ICH, NIHSS score, and ICH volume were included in the clinical model. Rad-score, instead of ICH volume, was included in the combined model. The combined model exhibited better discrimination ability and achieved an overall better benefit against threshold probability than the clinical model in the decision curve analysis (DCA). CONCLUSIONS: The combined radiomics-clinical model was better able to predict ICH-associated PSE compared to the clinical model. This can help clinicians better predict an individual patient's risk of PSE following a first-ever ICH and facilitate earlier PSE diagnosis and treatment. KEY POINTS: • Radiomics has not been used in predicting the risk of developing PSE. • Higher Rad-scores were associated with higher risk of developing PSE. • The combined model showed better performance of PSE prediction ability.

Spontaneous brainstem haemorrhage in a patient with uraemia undergoing initial hemodialysis: A case report.

The present study reports the case of an elderly male inpatient with uraemia who had a sudden onset of numbness and weakness in the right limbs during sleep at night, accompanied by blurred and double vision, during the induction of haemodialysis (HD). Cranial computed tomography and magnetic resonance imaging revealed signs of brainstem haemorrhage. Consequently, a proactive treatment approach was adopted for decreasing the blood and intracranial pressures of the patient, and regular HD was continued. The condition of the patient improved, and the limbs showed no impairment of sensation, with normal movement. To the best of our knowledge, this is the first reported case of an inpatient with uraemia undergoing HD who developed a sudden brainstem haemorrhage during the induction phase of HD and completely recovered after conservative treatment. This unusual case deserves the attention of all clinicians, who should pay more attention to the patients with spontaneous brainstem hemorrhage.

Epilepsy in Cerebrovascular Diseases: A Narrative Review.

BACKGROUND: Epilepsy is a common comorbidity of cerebrovascular disease and an increasing socioeconomic burden. OBJECTIVE: We aimed to provide an updated comprehensive review on the state of the art about seizures and epilepsy in stroke, cerebral haemorrhage, and leukoaraiosis. METHODS: We selected English-written articles on epilepsy, stroke, and small vessel disease up until December 2021. We reported the most recent data about epidemiology, pathophysiology, prognosis, and management for each disease. RESULTS: The main predictors for both ES and PSE are the severity and extent of stroke, the presence of cortical involvement and hemorrhagic transformation, while PSE is also predicted by younger age at stroke onset. Few data exist on physiopathology and seizure semiology, and no randomized controlled trial has been performed to standardize the therapeutic approach to post-stroke epilepsy. CONCLUSION: Some aspects of ES and PSE have been well explored, particularly epidemiology and risk factors. On the contrary, few data exist on physiopathology, and existing evidence is mainly based on studies on animal models. Little is also known about seizure semiology, which may also be difficult to interpret by non-epileptologists. Moreover, the therapeutic approach needs standardization as regards indications and the choice of specific ASMs. Future research may help to better elucidate these aspects.

PF4 induces inflammatory response through NF-kB signal pathway in rats with intracerebral haemorrhage.

Intracerebral haemorrhage (ICH) is a lethal cerebrovascular disorder with a high mortality and morbidity. Although it is a major public health problem, there is no effective treatment for ICH. After ICH, the primary and secondary mechanisms are mentioned when discussing brain injury. The transcription factor, nuclear factor-kappa B (NF-kB), is an important regulator of inflammatory responses. The role of platelet factor 4 (PF4) in ICH is unclear. To study the effect of PF4 on inflammatory response of rats in ICH, a rat model of striatum ICH was established by injecting autologous blood from the autogenous femoral artery into the right striatum of rats. Forty-eight hours after ICH, the expression of PF4, NF-kB (P-P65) and inflammatory changes in rats were determined with WB and ELISA. Heme was used to induce PC12 cell damage, simulate the ICH model in vitro, and detect PF4, P-P65 and striatal inflammatory changes. Short hairpin RNA (shRNA-PF4) was used to knock-down the expression of PF4 in PC12 cells to detect changes in inflammatory factors. The results showed that 48 hours after surgery, the behavioural score of cerebral haemorrhage was the lowest. The expression of PF4 and P-P65 in the striatum of the ICH group was significantly higher compared with the sham surgery group. The expression of interleukin (IL)-6 and IL-1b in the ICH group was also greatly improved. After inhibiting NF-kB expression, PF4 expression was decreased. In short, ICH enhances the expression of PF4, which induces an inflammatory response in rats with cerebral haemorrhage through the NF-kB signalling pathway. Reducing the expression of PF4 can attenuate the inflammatory response.

Pamiparib Induces Neurodevelopmental Defects and Cerebral Haemorrhage in Zebrafish Embryos via Inhibiting Notch Signalling.

Pamiparib is a poly ADP-ribose polymerase (PARP) inhibitor used in clinical studies, which can penetrate the blood-brain barrier efficiently. At present, there are few studies on its effect on vertebrate neurodevelopment. In this study, we exposed zebrafish embryos to 1, 2 and 3 µM of Pamiparib from 6 to 72 h post-fertilisation (hpf). Results showed that pamiparib can specifically induce cerebral haemorrhage, brain atrophy and movement disorders in fish larvae. In addition, pamiparib exposure leads to downregulation of acetylcholinesterase (AChE) and adenosine triphosphate (ATPase) activities, and upregulation of oxidative stress which then leads to apoptosis and disrupts the gene expression involved in the neurodevelopment, neurotransmitter pathways and Parkinson's disease (PD) like symptoms. Meanwhile, astaxanthin can partially rescue neurodevelopmental defects by downregulating oxidative stress. After exposure to pamiparib, the Notch signalling is downregulated, and the use of an activator of Notch signalling can partially rescue neurodevelopmental toxicity. Therefore, our research indicates that pamiparib may induce zebrafish neurotoxicity by downregulating Notch signalling and provides a reference for the potential neurotoxicity of pamiparib during embryonic development.

Noonan syndrome with RAF1 gene mutations in a newborn with cerebral haemorrhage.

BACKGROUND: Noonan syndrome is an autosomal dominant genetic disorder that can occur in men and women and has a sporadic or family history. NS can lead to abnormal bleeding, but cerebral haemorrhage is rare. This is the first case of cerebral haemorrhage with a RAF1 gene mutation that originated in the neonatal period. CASE PRESENTATION: This case presents a newborn with a RAF1 gene mutation resulting in NS complicated with an abnormality of chromosome 46, X, del (Y) (q12). In the course of treatment, the baby's breathing suddenly increased. After an MRI examination of the skull, haemorrhaging was found in multiple parts of the brain. CONCLUSIONS: After symptomatic treatment, the baby recovered well, but the main cause of cerebral haemorrhage was not found.