Cerebral Lesions Research Articles

Partial response to treatment with ALK inhibitor in a patient with SQSTM1-ALK fusion positive lung adenocarcinoma

Introduction: Lung cancer is the second most common cancer worldwide and the leading cause of cancer deaths; non-small cell lung cancer (NSCLC) constitutes about 85% of lung cancer cases, with ALK fusions representing 3–6% of them. The SQSTM1-ALK fusion is a rare finding in NSCLC, accounting for only 1.1% of ALK rearrangements. We present a case of lung adenocarcinoma with documentation of SQSTM1-ALK fusion that showed a partial response to alectinib. Case description: This case details the clinical course of a 71-year-old, non-smoking woman with no significant medical history who presented with confusion, aphasia and multiple cerebral lesions detected on imaging. Further investigations revealed a stage IV lung adenocarcinoma with metastases to the brain and adrenal gland. Molecular profiling identified a rare SQSTM1-ALK fusion mutation alongside other genetic abnormalities, including low programmed death-ligand 1 expression and ROS1 kinase protein presence. Treatment with alectinib, initiated based on the identified ALK fusion, resulted in significant tumour regression in the lungs and complete resolution of the adrenal mass, as evidenced by follow-up imaging and clinical assessments. Conclusion: This case highlights the efficacy of alectinib in treating rare ALK fusion variants in and underscores the importance of comprehensive molecular profiling in guiding targeted therapy decisions.

Grade prediction of lesions in cerebral white matter using a convolutional neural network.

We established a diagnostic method for cerebral white matter lesions using MRI images and examined the relationship between the MRI images and the medical checkup data. There were approximately 25 MRI images for each patient's head, from the top of the head to near the eyes. To order these images, we defined the unit of axial for convenience. We varied conditions, such as the location and extent of the images to be loaded, into a convolutional neural network model and verified the changes in discrimination performance on the test data. Co-occurrence network diagrams were also used to determine the relationship between the grade of cerebral white matter lesions and the biochemical test items, which were treated as categorical variables, the progression of cerebral white matter lesions, and patient health status. The convolutional neural network showed the highest discrimination performance when the images were loaded into the model with 80 pixels per side, axial from 9 to 15, along with FLAIR and T1-weighted images. The area under the curve for each grade was 0.9814 for grade 0, 0.9800 for grade 1, 0.9905 for grade 2, 0.9977 for grade 3, and 0.9998 for grade 4. In the co-occurrence network diagram, patients with no or mild cerebral white matter lesions, such as grade 0 and grade 1, had near normal blood pressure, whereas grade 2 patients were closer to (isolated) systolic hypertension. This indicates that patients with higher-grade cerebral white matter lesions tend to experience more severe hypertension.

NCOG-06. FACTORS ASSOCIATED WITH SOCIAL DISABILITY IN THE CHRONIC POSTOPERATIVE PERIOD IN PATIENTS WITH GLIOMAS

Abstract BACKGROUND Patients with low-grade gliomas may have no obvious problems during hospitalization or their initial return to social life; however, social life difficulties may gradually become more apparent long after the surgery. We investigated factors associated with social disabilities in patients with low-grade gliomas in the postoperative chronic phase. METHODS The study included 114 patients with WHO grade 2 or 3 gliomas who underwent surgery (mean age, 44.3±13.2 years). Seventy-six patients underwent an initial surgery and 38 underwent a second surgery. All patients underwent various brain functional assessments and interviews about their social lives over 1 year after the surgery (median, 23 months). Factors associated with social disabilities were determined using logistic multiple regression analysis and chi-square tests. Voxel-based lesion symptom mapping was used to examine the brain regions associated with social disabilities. RESULTS Social disabilities were observed in 12.3% of the patients. Factors associated with social disabilities were the number of surgeries (first vs. second, p=0.0052) and tumor location (left vs. right, p=0.0091). Patients with recurrence and right cerebral hemispheric lesions had a higher probability of social disability (42.1%, p<0.0001) than that of other patients. The reasons for social disability after right hemispheric recurrence were social behavior disorder (62.5%) and neuropsychological dysfunctions (37.5%). Social behavioral disorders include interpersonal problems, such as job switching owing to problems with others, poor interpersonal relationships, and sexually deviant behavior. No other apparent neuropsychological abnormalities were found in patients with social behavior disorders. Surgical resection of the deep part of the right prefrontal area is associated with social behavior disorders and right supplementary motor cortex resection is associated with neuropsychological disorders. CONCLUSION In lower grade glioma, patients with right hemispheric recurrence were more likely to develop social disabilities in the chronic phase, which was caused by social behavioral disorders and neuropsychological dysfunctions.

Cerebrospinal fluid neurofilament light chain levels in children with acquired demyelinating syndrome

ObjectiveTo study the cerebrospinal fluid (CSF) neurofilament light chain (NfL) in pediatric acquired demyelinating syndrome (ADS) and its association with factors of laboratory and imaging results.MethodsWe analyzed clinical data from children with ADS collected from May 2020 to January 2021 at the Department of Neurology of Guangzhou Women and Children's Medical Center. Enzyme-linked immunosorbent assays were used to detect the CSF NfL of patients.ResultsThirty pediatric ADS patients (17 male, 13 female) were included in the study. The most frequent diagnosis was uncategorized ADS (36.7%, 11/30), followed by acute disseminating encephalomyelitis (ADEM) (23.3%, 7/30), myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) (20.0%, 6/30), NMO (6.7%, 2/30), multiple sclerosis (MS) (6.7%, 2/30), and neuromyelitis optic spectrum disorders (NMOSD) (6.7%, 2/30). The median CSF NfL for the first time was 7,425.28 pg/ml (interquartile range, 1,273.51, >10,000 pg/ml). CSF NfL increase over normal value (<290.00 pg/ml for people younger than 30 years old) was seen in 98.7% of patients. Patients were divided into uncategorized ADS, ADEM, MOGAD, and MS/NMO/NMOSD groups, with no significant difference in CSF NfL between each group. The CSF NfL positively correlated with the immunoglobulin (Ig) G (ρ = 0.473) and IgE (ρ = 0.366). However, the CSF NfL did not correlate with CSF white blood count and CSF protein. Furthermore, there was no significant difference between patients with oligoclonal bands positive and without. The CSF NfL negatively correlated with interferon γ (ρ = −0.501), CD45 + CD3+ T (ρ = −0.466), CD45 + CD3 + CD4+ T (ρ = −0.466), and CD45 + CD3 + CD8+ T cells (ρ = −0.521). However, it did not correlate with CD45 + CD19+ B cells. CSF NfL in patients with cerebral white matter lesions in MRI was higher than in patients without. Moreover, the CSF NfL positively correlated with the number of brain MRI locations (ρ = 0.362). Nine patients underwent multiple detections of CSF NfL, and their CSF NfL for the last detection was not significantly different from the first.ConclusionsThe CSF NfL increases significantly in pediatric ADS, and it can be a biomarker of neuro-axonal injury and a good indication of the extent of lesions.

Evaluation of Brain and Spinal Cord Lesions and Cerebrospinal Fluid Analysis in Detecting Demyelinating Diseases in Patients with Optic Neuritis

ABSTRACT Optic neuritis can be an early sign of demyelinating diseases like multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). We investigated the presence or absence of head and spinal cord lesions on magnetic resonance imaging (MRI) and assessed whether cerebrospinal fluid (CSF) tests are useful in detecting demyelinating disease in patients with first diagnosed optic neuritis. We conducted a retrospective study of 111 patients (47 idiopathic, 19 NMOSD, 16 MOGAD, 16 MS, 6 optic neuritis with cerebral lesions but that does not meet the McDonald’s criteria for MS (ON+)), and 7 chronic relapsing inflammatory optic neuropathy) diagnosed with optic neuritis without cerebral or spinal symptoms. Patients underwent evaluations including orbital, head, and spine MRI, along with CSF analysis. Among the 111 patients, 20 (35.1%: 4 NMOSD, 4 MOGAD, 7 MS, and 6 ON+) exhibited intracerebral or spinal cord lesions. Twelve patients showed findings on both orbital and head MRI, while six had no orbital MRI findings except for optic neuritis but exhibited lesions on head MRI. Five patients had spinal lesions without intracerebral lesions. CSF analysis revealed positive oligoclonal bands and elevated myelin basic protein levels indicate the high likelihood with systemic inflammatory demyelinating diseases. Even in the absence of concomitant encephalitis or myelitis symptoms or a history of these conditions, MRI images of patients with optic neuritis sometimes reveal lesions in the brain or spinal cord. CSF abnormalities were indicative of systemic demyelinating disease presence, extending beyond MS to NMOSD and MOGAD.

FIRST-IN-HUMAN EXPERIENCE OF HIGH ENERGY ELECTROPULSE PULSED FIELD ABLATION: ACUTE RESULTS FOR PULMONARY VEINS AND POSTERIOR WALL ISOLATION

Different iterations of catheter and energy delivery system configurations are evolving for pulsed field ablation (PFA); however, some have used large and complex catheters, required large sheaths and had a recognised risk of haemolysis. To evaluate the acute safety and efficacy of a custom designed 8F variable loop multielectrode mapping and PFA catheter with contact sensing. This acute feasibility study recruited 30 patients undergoing de novo ablation of paroxysmal or persistent atrial fibrillation (AF). The ElectroPulse Study is a first-in-human, non-randomised, prospective study of a novel PFA system that utilizes an 8F 10-electrode variable loop steerable mapping and ablation catheter with 2800V biphasic bipolar waveform. All patients had pulmonary vein (PV) and posterior wall isolation (PWI) using the PFA system. The main outcomes were the acute success of PV/PWI and peri-procedural serious adverse events. Complete PV/PWI was successfully achieved in all 30 patients with 59.7±7.2 applications. Total procedural time was 113.6±26.3 mins with fluoroscopy time of 8.0±5.5 mins and LA dwell time of 78.7±18.6 mins. There was no esophageal injury, phrenic nerve palsy, clinical stroke or death. Brain MRI detected 2 new but transient silent cerebral lesions. Two patients (6.7%) had vascular access complications. Although there were changes in the biomarkers for hemolysis, none of the patient experienced clinical hemolysis or related acute kidney injury. This first-in-human study demonstrated that PFA using a novel variable loop catheter with a contact sensing system safely achieved 100% acute PVI/PWI with safety profile comparable to existing PFA systems.

Multidomain cognitive improvement in patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation

Abstract Background Cognitive impairment is prevalent in one third of patients with symptomatic severe aortic valve stenosis scheduled for transcatheter aortic valve implantation (TAVI). How TAVI affects cognitive functioning in these patients remains unknown. Purpose The CAPITA study (CArdiac outPut, cerebral blood flow and cognition In patients with severe aortic valve stenosis undergoing Transcatheter Aortic valve implantation) assessed the effects of TAVI on cerebral lesions and cognitive functioning. Methods CAPITA is a prospective study of cerebral and cognitive outcomes in 148 patients undergoing TAVI. One day before and three months after TAVI, patients underwent a standardized multidomain neuropsychological assessment, and simultaneous brain magnetic resonance imaging. The primary outcome was change in global cognitive functioning as measured with z-scores. Also, we assessed the cognitive subdomains of attention/psychomotor speed, memory, language, and executive functioning. Z-scores for each cognitive domain were constructed as: (test score - mean baseline score) / standard deviation. Global cognitive function was calculated as the mean from the four domain scores. Results Mean age was 80.5±5.7 years, 43% was female and median STS-PROM (Society for Thoracic Surgeons Predicted Risk for 30-day Mortality) was 2.0% (IQR 1.4%-2.9%). MoCA scores improved from 23.3±3.7 to 24.4±3.3, (p<0.001) and MMSE scores from 26.4±2.6 to 26.9±2.4 (p=0.01). There was an overall increase in global cognitive z-scores (0.02±0.52 to 0.15±0.48, p<0.001). Cognitive domains of memory (0.03±0.77 to 0.18±0.80, p=0.003) and language (-0.07±1.07 to 0.20±0.80, p=0.02) significantly improved, whereas executive function (0.01±0.70 to 0.06±0.76, p=0.42) and attention (0.10±0.69 to 0.17±0.69, p=0.06) did not significantly change. Quality of life on the visual analogue scale improved from 66.4±15.9 to 72.9±12.8, (p<0.001). Patients in the lowest tertile of baseline cognitive functioning (i.e., those with worst baseline cognitive functioning), had the largest increase in cognitive functioning, compared with patients in the intermediate or highest tertile of baseline cognitive functioning (0.30±0.55 vs 0.09±0.27 vs 0.01±0.16, p=0.002). Patients with >0.5 SD decline in cognitive functioning (12%), had a higher volume of new white matter hyperintensities on follow-up MRI than patients with stable or improved cognitive functioning (1.26±2.96, vs 0.29±0.45 vs 0.31±0.91 mL, p=0.06). Conclusions In 148 patients who underwent TAVI, there was an overall improvement in cognitive functioning at three months follow-up. This improvement was consistent through different cognitive domains and most prominent in patient with lowest baseline cognitive functioning.Change in cognitive functionin

Association between silent cerebral embolism and cognitive alterations following transcatheter aortic valve replacement in bicuspid versus tricuspid aortic valve patients

Abstract Background Silent cerebral ischemic lesions (SCILs) is a common magnetic resonance imaging (MRI) finding in severe aortic stenosis patients post - transcatheter aortic valve replacement (TAVR). We evaluated the association between SCILs and cognitive alterations in patients with bicuspid aortic valve (BAV) versus tricuspid aortic valve (TAV) post-TAVR. Methods This study enrolled 100 consecutive TAVR (45 with BAV and 55 TAV). DW-MRI and neurocognitive evaluation (MoCA score) were performed at baseline, discharge, and 1- and 12-month post-discharge. Results Ninety-two out of the 100 patients (92%) exhibited cognitive dysfunction at baseline. Post-TAVR, overall cognitive function significantly improved, the average MOCA score increased from 18.69±6.74 to 22.18±6.30. During the 1-year follow-up, 54 patients demonstrated improved cognitive function, and the number of patients with moderate-to-severe cognitive dysfunction (MoCA score < 18) significantly decreased from 32 to 16. Prevalence of SCILs was 14% and 72% at baseline and discharge, respectively. New SCILs were observed in 60 patients at discharge, distributed across all vascular territories, averaging 4 lesions with a total volume of 215.4±195.4mm3. Although no significant correlation existed between total volume of new SCILs and cognitive changes post-TAVR (R=-0.133, p=0.206), patients with SCILs still displayed significant cognitive improvement (MoCA score from 18.4±6.6 to 22.0±7.1), whereas patients who developed large SCILs (lesion diameter >9) showed less improvement compared to those with small or median SCILs (number of patients who had cognitive improvement: 32 vs. 52, p<0.05). Cognitive function improvement post-TAVR did not significantly differ between BAV and TAV patients, MoCA scores were comparable (BAV group, n=45, from 18.63±6.68 to 21.88±6.80 vs. TAV group, n=55, from 18.73±6.81 to 22.42±5.80; p>0.05). DW-MRI revealed more new SCILs in BAV patients post-TAVR compare to TAV patients (235 lesions vs. 150 lesions, respectively). In BAV patients, SCILs primarily manifested in small and medium sizes (224 lesions), despite more severe calcification (valvular calcium volume 956.5±644.0 mm vs. 634.4±508.0 mm3; p=0.028). The number of large lesions was similar in the two groups (11 in BAV group and 10 in TAV group). Conclusion TAVR demonstrates positive effects on improving cognitive function in aortic stenosis patients, despite common occurrence of SCILs in both BAV and TAV patients. Cognitive function post-TAVR was comparable between BAV and TAV patients. The cognitive improvement from TAVR may be less impacted by small- and medium-sized SCILs, while severe SCILs might impede or diminish the cognitive benefits of TAVR.table

Trousseau syndrome with recurrent cerebral infarction as the first oneset in a gastrointestinal malignant tumor patient: A case report.

Trousseau syndrome (TS) is a thrombosis disorder characterized by a hypercoagulable state linked to underlying malignancies, resulting in various thrombotic events such as deep vein thrombosis, pulmonary embolism, and arterial thrombosis. This syndrome serves as a crucial indicator of malignancy and can often be the first sign of an underlying tumor. In this case, we report a case of gastrointestinal malignant tumor as the first onset, and analyzes its clinical characteristics to improve the clinicians' understanding of this kind of disease. A 69-year-old woman was admitted to the hospital 4 times in 1 month for cerebral infarction. The patient was admitted several times with a new cerebral infarction lesion and a high D-dimer level, a persistently positive fecal occult blood test, and a gastrointestinal tumor was later found. The patient was diagnosed with TS, attributed to her underlying malignancy. During hospitalization, the patients were treated with aspirin for antiplatelet, esomeprazole for protection of gastric mucosa, atorvastatin for lowering blood lipids, butylphthalein for improvement of collateral circulation, edaravone dextrocamphorol for scavenging oxygen free radicals, and betahistine hydrochloride tablets for preventing dizziness. The patient's condition improved significantly after initial treatment, but died of the tumor a year after discharge. Currently, TS has a complex and varied clinical presentation and is relatively difficult to diagnose, especially in patients with an unknown tumor history. Focus should be placed on patients with recurrent cerebral infarctions and increased D-dimer levels, and anticoagulation may be an effective treatment for patients with TS.

The Neck-Crossing Technique Using the Low-Profile Distal Access Catheter in Flow Diverter Placement for Dissecting Posterior Cerebral Artery Aneurysm: A Case Report

AbstractWe report a case in which a novel distal access catheter proved successful in the placement of a flow diverter for a challenging distal cerebral artery lesion. We discuss the advantages and pitfalls of this technique and considerations for its use. A 74-year-old female presented with intermittent headaches, and was diagnosed with a dissecting aneurysm at the proximal right posterior cerebral artery with a sharp bleb, measuring 9.8 mm in diameter. Given the complex vascular anatomy, stent-assisted coil embolization was initially considered but deemed high risk for dual catheter for jailing technique with 6-Fr size guiding catheter due to the tortuosity and stenosis of the parent vessel. Therefore, we opted for flow diverter treatment, which presented its challenges during delivery. By employing a low-profile distal access catheter, Phenom Plus (outer diameter: 4.2-Fr. inner diameter: 1.13 mm; Medtronic, Minneapolis, Minnesota, United States), with a minimal ledge between it and the delivery catheter, Phenom 27 (outer diameter: 2.8-Fr, 0.91 mm; Medtronic), we successfully crossed the neck of the aneurysm with Phenom Plus and placed the flow diverter. While acknowledging potential risks, this case demonstrates the value of the neck-crossing technique using a low-profile distal access catheter as an alternative option for treating challenging peripheral artery aneurysms with flow diverters. This technique offers promise in specific situations where conventional methods pose challenges.

Trajectory of mean platelet volume changes after aneurysmal subarachnoid hemorrhage in patients with or without delayed cerebral ischemia

The morbidity of aneurysmal subarachnoid hemorrhage (aSAH) remains high, particularly because of secondary cerebral lesions that significantly aggravate the primary lesions. The main type of secondary lesions is delayed cerebral ischemia (DCI), in which platelets (PLT) appear to play a key role. Mean platelet volume (MPV) is an indirect marker of platelet activation. We aimed to determine the individual trajectories of MPV over time in patients with and without DCI during the course of aSAH. This is a single-center, retrospective, longitudinal analysis of individual trajectories of MPV over time, in a cohort of aSAH patients included in the Prospective, Observational Registry of Patient with Subarachnoid Hemorrhage in Neurocritical Care Unit (ProReSHA). A mixed-effects linear regression model was used to compare the trajectories of MPV and MPV/PLT ratio between patients who developed a DCI and those who did not. A total of 3634 MPV values were collected in 587 patients. The analysis of MPV as a function of DCI occurrence showed a significant difference in the trajectory over time between patients with DCI and those without, with an estimate of 0.02 (95%CI 0.01, 0.04, p = 0.009). The analysis of the MPV/PLT ratio as a function of DCI occurrence and other covariates showed a significant difference in the trajectory over time only for patients with a modified Fisher score less than 3, with an estimate of -0.59 (95%CI: -0.94, -0.23, p = 0.001). The individual trajectories of MPV over time differ between patients with DCI and those without. However, MPV values vary greatly over time and between patients. Thus it does not appear as a reliable biomarker for stratifying patients based on their specific risk of developing DCI. ClinicalTrials.gov identifier: (NCT02890004), registered in August 2016.

Impact of caring for patients with polyhandicap on institutional health care workers' quality of life: a cross-sectional and longitudinal evaluation.

Profound intellectual multiple disabilities or polyhandicap (PLH) is defined as a combination of profound mental retardation and serious motor deficits resulting in extreme dependence. Support for these patients is multidisciplinary, complex, and time-consuming. Thus, institutional health care workers (HCWs) face specific working conditions: frequent physical tasks, distressed families, and restricted feedback. We aimed to identify determinants of quality of life (QoL) of HCWs and to study longitudinal evolution. The study used data from the French cohort EVAL-PLH. The participants were institutional HCWs of persons with PLH (age ≥ 3 years at the time of inclusion; age at onset of cerebral lesion <3 years old). Two populations were used: (1) cross sectional study: the sample 1 includes the HCWs assessed at T2 (2020-2021); (2) longitudinal study: the sample 2 includes the HCWs assessed at both T1 (2015-2016) and T2 (2020-2021). The data collected included: sociodemographics, health status, professional variables, and psycho-comportemental aspects. QoL was assessed using WHOQOL-BREF which provides 4 scores. In comparison with French norms, the physical and social scores of QoL were significantly lower while the psychological score was significantly higher for (i) the 223 HCWs (participation rate 62%) assessed at T2 and (ii) the 61 HCWs assessed at T1 and T2. The main factors modulating QoL were age, marital status, self-perceived financial difficulties, personal chronic disease, anxiety-mood disorders, nature of coping strategies, and burnout. This study confirms the mixed (negative and positive) impact of caring persons with PLH on the institutional HCWs' QOL. Main determinants of the HCW's QOL were: older age, single status, perceived financial difficulties, altered health status, burn out and coping strategies.Clinical trial registration number: NCT02400528.

Incidence of drug dependence and epilepsy in patients with PTC (Post Traumatic Contusions) manage conservatively. A prospective study.

Objective: To explore the presence of drug dependence and Epilepsy in patients with PTC (Post Truamatic Contusions) balanced cautiously. Study Design: Proposed Reviewed Research study. Setting: Hayatabad Medical Complex, Peshawar. Period: July 2020 to December 2020. Methods: About 90% of patients aged between fifteen to sixty-five years old identified with cerebral lesion and balanced cautiously were applied. Follow up sessions was provided to patients for 12to 18 months. Results: Among the enrolled patients, 23% established early PTS (Post Traumatic Seizures) and approximately established late PTS (Post Traumatic Seizures) from mild to moderate level of cerebral lesion. Patients having early signs of Post traumatic Seizure, about 6% utilized AEDs (Anti-epileptic Drugs) for about 3 months throughout the treatment period and about 7% of patients along with late Post Traumatic Seizures utilized AEDs. Moreover, approximately 8 percent patients established late post traumatic Seizure without considering any early signs of condition. Research findings indicated that only 3% of patients with early and late PTS actually required AEDs for at least 6 months. Although, about 44 percent of patients were utilizing Anti-epileptic drugs to control seizures. Sensible usage of Anti-epileptic drugs is familiar in our region, contributing to enhanced danger of medicine opposition and acquiring financial pressure on low-paid people in well-established state. Additionally, extreme usage of anti-epileptic and prophylactic drugs doesn’t impact the occurrence of PTE (Post Traumatic Epilepsy). Conclusion: The presence of late and early post-traumatic epilepsy observed within our study is contrast to that explored in another research. Sensible production of AEDs is occured in our state, that increases the danger of medicine opposition and attain financial issues for economically destruct people in well-established states. Extreme usage of AEDs and prophylactic drugs doesn’t have an important influence on stopping PTE.

Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Replacement: A Review.

Cerebrovascular events (CVEs) are a dreaded complication of transcatheter aortic valve replacement (TAVR). They are associated with significant mortality, morbidity, and reduced quality of life and impose a significant burden to health care systems. Although the rates of clinical stroke have reduced since the advent of TAVR, it remains an important complication, particularly as TAVR is increasingly utilized. CVE may occur at the time of the TAVR, as a direct consequence of the procedure, or may occur later, related to thrombosis of the prosthetic valve, atrial fibrillation, and other comorbidities. Imaging of the brain has revealed a high prevalence of subclinical cerebral infarcts (68%-98%) associated with the TAVR procedure. Although their clinical significance has not been fully established, clinically evident CVE ranges between 3% and 5% in patients considered at high operative risk to between 1% and 3% in low operative risk patients. Periprocedural CVEs are largely the result of embolization of the thrombus and tissue derived from the valve, vasculature, or myocardium. Cerebral embolic protection devices have been studied in multiple trials, with some evidence supporting a reduction in new cerebral lesion volume, number, and potentially disabling strokes. However, thus far, there is no robust evidence that they reduce the overall stroke rate. The number and severity of comorbidities, in particular, new-onset atrial fibrillation, are associated with CVEs. Valve thrombosis diagnosed using computed tomography as areas of hypoattenuated leaflet thickening has been identified in 10% to 15% of patients. This is a dynamic process associated with an increase in CVEs, but that resolves with anticoagulation or sometimes without it. Routine use of anticoagulation compared with a single antiplatelet agent is associated with an increased risk of bleeding, without any additional alleviation in risk of thromboembolism. Future studies to improve risk stratification could facilitate the tailoring of preventive therapies to patients at high risk of CVE, who stand to gain the most benefit.

Health status of individuals with polyhandicap across a 5-year follow-up period

The present longitudinal study examined a large sample of individuals with PIMD/Polyhandicap to: (i) describe the evolution over time of the health status in terms of severity, (ii) identify the potential predictors of health status change. This study used the data of the French national EVAL-PLH cohort. Inclusion criteria were: individuals with PIMD/Polyhandicap; age > 3 years at the time of inclusion; age at onset of cerebral lesion younger than 3 years old. The definition of the change in health status over the 5-year period was derived from the Polyhandicap Severity Scale. Among the 875 individuals included in 2015–2016, 492 (56.2%) individuals were assessed in 2020–2021. According to the definition, 68.8% (n = 309), 64.7% (n = 310), and 80.2% (n = 368) of the individuals presented with a worsened or stable severity status based on the global score, the abilities score, and the comorbidities score, respectively. Compared with the individuals with a non-worsened health status (global score), the individuals with a stable or worsened health status were more likely to receive care in specialized rehabilitation centres, more likely to have an antenatal or progressive aetiology, and more likely to have a higher dependency level. The current study provides a robust perspective of the worsened health among persons with PIMD/Polyhandicap over time.

Enforced HCELL Expression Enhances Bone Marrow Stromal Cells Homing and Amelioration of Cerebral Ischemia-Reperfusion Injury via induction of PGE2.

Ischemic stroke (IS) is a significant and potentially life-threatening disease with limited treatment options, often resulting in severe disability. Bone marrow stromal cells (BMSCs) transplantation has exhibited promising neuroprotection following cerebral ischemia-reperfusion injury (CIRI). However, the effectiveness is hindered by their low homing rate when administered through the vein. In this study, we aimed to enhance the homing ability of BMSCs through lentivirus transfection to express fucosyltransferase 7. This glycosylation engineered CD44 on BMSCs to express hematopoietic cell E-selectin/L-selectin ligand (HCELL), which is the most potent E-selectin ligand. Following enforced HCELL expression, the transplantation of BMSCs was then evaluated in a middle cerebral artery occlusion (MCAO) model. Results showed that HCELL+BMSCs significantly ameliorated neurological deficits and reduced the volume of cerebral infarction. Furthermore, the transplantation led to a decrease in apoptosis by up-regulating BCL-2 and down-regulating BAX, also reduced the mRNA levels of inflammatory factors, such as interleukin-1β (IL-1β), IL-2, IL-6 and tumor necrosis factor-alpha (TNF-α) in the ischemic brain tissue. Notably, enforced HCELL expression facilitated the migration of BMSCs towards cerebral ischemic lesions and their subsequent transendothelial migration through the up-regulation of PTGS-2, increased production of PGE2 and activation of VLA-4. In summary, our study demonstrates that transplantation of HCELL+BMSCs effectively alleviates CIRI, and that enforced HCELL expression enhances the homing of BMSCs to cerebral ischemic lesions and their transendothelial migration via PTGS-2/PGE2/VLA-4. These findings indicate that enforced expression of HCELL on BMSCs could serve as a promising therapeutic strategy for the treatment of ischemic stroke.

Comparing stand-alone endovascular embolization versus stereotactic radiosurgery in the treatment of arteriovenous malformations with Spetzler-Martin grades I–III: a propensity score matched study

BackgroundArteriovenous malformations (AVMs) are uncommon cerebral lesions that can cause significant neurological complications. Surgical resection is the gold standard for treatment, but endovascular embolization and stereotactic radiosurgery (SRS) are viable...

Potentiation of cortico-spinal output via targeted electrical stimulation of the motor thalamus

Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for therapies aimed at improving volitional muscle activation. Here we hypothesize that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby immediately potentiating motor output. To test this hypothesis, we identify optimal thalamic targets and stimulation parameters that enhance upper-limb motor-evoked potentials and grip forces in anesthetized monkeys. This potentiation persists after white matter lesions. We replicate these results in humans during intra-operative testing. We then design a stimulation protocol that immediately improves strength and force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions.

Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage

BackgroundGenetic variants in COL4A2 are less common than those of COL4A1 and their fetal clinical phenotype has not been well described to date. We present a fetus from China with an intronic variant in COL4A2 associated with a prenatal diagnosis of severe cerebral encephalomalacia and subdural hemorrhage.MethodsWhole exome sequencing (WES) was applied to screen potential genetic causes. Bioinformatic analysis was performed to predict the pathogenicity of the variant. In in vitro experiment, the minigene assays were performed to assess the variant’s effect.ResultsIn this proband, we observed ventriculomegaly, subdural hemorrhage, and extensive encephalomalacia that initially suggested cerebral hypoxic-ischemic and/or hemorrhagic lesions. WES identified a de novo heterozygous variant c.549 + 5G > A in COL4A2 gene. This novel variant leads to the skipping of exon 8, which induces the loss of 24 native amino acids, resulting in a shortened COL4A2 protein (p.Pro161_Gly184del).ConclusionOur study demonstrated that c.549 + 5G > A in COL4A2 gene is a disease-causing variant by aberrant splicing. This finding enriches the variant spectrum of COL4A2 gene, which not only improves the understanding of the fetal neurological disorders associated with hypoxic-ischemic and hemorrhagic lesions from a clinical perspective but also provides guidance on genetic diagnosis and counseling.

The association between maternal immune activation and brain structure and function in human offspring: a systematic review.

Maternal immune activation (MIA) during pregnancy, as a result of infectious or inflammatory stimuli, has gained increasing attention for its potential role in adverse child neurodevelopment, with studies focusing on associations in children born preterm. This systematic review summarizes research on the link between several types of prenatal MIA and subsequent child structural and/or functional brain development outcomes. We identified 111 neuroimaging studies in five MIA areas: inflammatory biomarkers (n = 13), chorioamnionitis (n = 18), other types of infections (n = 18), human immunodeficiency virus (HIV) (n = 42), and Zika virus (n = 20). Overall, there was large heterogeneity in the type of MIA exposure examined and in study methodology. Most studies had a prospective single cohort design and mainly focused on potential effects on the brain up to one year after birth. The median sample size was 53 participants. Severe infections, i.e., HIV and Zika virus, were associated with various types of cerebral lesions (e.g., microcephaly, atrophy, or periventricular leukomalacia) that were consistently identified across studies. For less severe infections and chronic inflammation, findings were generally inconsistent and mostly included deviations in white matter structure/function. Current findings have been mainly observed in the infants' brain, presenting an opportunity for future studies to investigate whether these associations persist throughout development. Additionally, the inconsistent findings, encompassing both regions of interest and null results, call into question whether prenatal exposure to less severe infections and chronic inflammation exerts a small effect or no effect on child brain development.