[Analysis of the safety, accuracy, and factors influencing bleeding complications in CT-guided puncture biopsy of brain occupying lesions].

Objective: To investigate the safety and accuracy of CT-guided intracranial puncture biopsy and the possible influencing factors of postoperative bleeding complications. Methods: A case series study. A retrospective analysis was conducted on 101 patients who underwent CT-guided intracranial puncture biopsy at the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021. The basic data of patients and the safety and accuracy of CT-guided intracranial puncture biopsy were analyzed statistically. Univariate and multivariate logistic regression analysis were used to screen the influencing factors of bleeding complications in CT-guided intracranial puncture biopsy, and the bleeding complications in glioma subgroup were analyzed. Results: Among the 101 patients, 53 were males and 48 were females, aged (53.7±17.2) years. The average diameter of intracranial lesions was (3.5±1.4) cm, while the vertical distance from the lesion to the meninges was (2.4±1.7) cm. The needle's intracranial depth reached (3.2±1.8) cm, with adjustments averaging (3±1) occurrences and an average procedural duration of (40.2±12.9) minutes. Pathological diagnoses included glioma (36 cases), gliosis (3 cases), lymphoma (32 cases), metastatic tumors (7 cases), inflammatory lesions (13 cases), and 10 indeterminate cases. The positive rate of puncture pathology was 90.1% (91/101), and the diagnostic coincidence rate was 94.0% (78/83). The incidence of bleeding complications in CT-guided intracranial puncture biopsy was 26.7% (27/101), of which 23 cases had small intratoma or needle path bleeding, 4 cases had massive bleeding, and 2 cases died. The patients were divided into bleeding group (n=27) and no bleeding group (n=74), according to the presence or absence of bleeding. The results of univariate logistic regression analysis showed that thrombin time≥15 s and the number of needle adjustment were the factors affecting the occurrence of bleeding complications (both P<0.05), and the results of multivariate logistic regression showed that thrombin time≥15 s was the related factor for bleeding. Patients with thrombin time≥15 s had a 3.045 times higher risk of bleeding than those with thrombin time<15 s (OR=3.045,95%CI:1.189-7.799,P=0.020). Among the 101 patients, 36 cases of midbrain glioma were divided into low-grade glioma group (n=11) and high-grade glioma group (n=25) according to the pathological grade. Subgroup analysis showed that the risk of bleeding for high-grade gliomas was 9.231 times higher than that for low-grade gliomas (OR=9.231,95%CI:1.023-83.331,P=0.031). Conclusions: CT-guided intracranial puncture biopsy is safe and feasible with high accuracy. Complication rates are associated with thrombin time≥15 s, especially high-grade glioma, which increases the risk of postoperative bleeding.

Automatic brain-tumor diagnosis using cascaded deep convolutional neural networks with symmetric U-Net and asymmetric residual-blocks.

The use of various kinds of magnetic resonance imaging (MRI) techniques for examining brain tissue has increased significantly in recent years, and manual investigation of each of the resulting images can be a time-consuming task. This paper presents an automatic brain-tumor diagnosis system that uses a CNN for detection, classification, and segmentation of glioblastomas; the latter stage seeks to segment tumors inside glioma MRI images. The structure of the developed multi-unit system consists of two stages. The first stage is responsible for tumor detection and classification by categorizing brain MRI images into normal, high-grade glioma (glioblastoma), and low-grade glioma. The uniqueness of the proposed network lies in its use of different levels of features, including local and global paths. The second stage is responsible for tumor segmentation, and skip connections and residual units are used during this step. Using 1800 images extracted from the BraTS 2017 dataset, the detection and classification stage was found to achieve a maximum accuracy of 99%. The segmentation stage was then evaluated using the Dice score, specificity, and sensitivity. The results showed that the suggested deep-learning-based system ranks highest among a variety of different strategies reported in the literature.

Case report: Atypical case of autoimmune glial fibrillary acidic protein astrocytopathy following COVID-19 vaccination refractory to immunosuppressive treatments.

A 54-year-old Japanese man presented with headache and fever the day after SARS-CoV-2 vaccination. He became deeply unconscious within a week. Brain MRI showed periventricular linear enhancements and a few spotty lesions in the cerebral white matter. Cerebrospinal fluid (CSF) testing showed mild pleocytosis. He was treated with intravenous methylprednisolone and plasma exchange. However, the white matter lesions enlarged to involve the brainstem and cerebellum, and long cord spinal lesions appeared. Anti-glial fibrillary acidic protein (GFAP) antibody was positive in the CSF and serum, and he was therefore diagnosed as autoimmune GFAP-astrocytopathy (GFAP-A). In addition, high-dose immunoglobulin therapy was administered twice, but his symptoms did not improve; the white matter lesions enlarged further, and modified Rankin Scale score increased to 5. A brain biopsy specimen showed infiltration of macrophages and CD4 + lymphocytes together with neuron and oligodendrocytic injuries and glial scar. Although GFAP-A generally responds well to steroids, the present case developed GFAP-A following SARS-CoV-2 vaccination, with refractory to intensive immunosuppressive therapy and atypical pathologic findings of infiltration of CD4 + lymphocytes and demyelination.

CCR2+ monocytes replenish border-associated macrophages in the diseased mouse brain.

Border-associated macrophages (BAMs) are tissue-resident macrophages that reside at the border of the central nervous system (CNS). Since BAMs originate from yolk sac progenitors that do not persist after birth, the means by which this population of cells is maintained is not well understood. Using two-photon microscopy and multiple lineage-tracing strategies, we determine that CCR2+ monocytes are significant contributors to BAM populations following disruptions of CNS homeostasis in adult mice. After BAM depletion, while the residual BAMs possess partial self-repopulation capability, the CCR2+ monocytes are a critical source of the repopulated BAMs. In addition, we demonstrate the existence of CCR2+ monocyte-derived long-lived BAMs in a brain compression model and in a sepsis model after the initial disruption of homeostasis. Our study reveals that the short-lived CCR2+ monocytes transform into long-lived BAM-like cells at the CNS border and subsequently contribute to BAM populations.

Human-Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Showed Neuronal Differentiation, Neurite Extension, and Formation of Synaptic Structures in Rodent Ischemic Stroke Brains.

Ischemic stroke is a major cerebrovascular disease with high morbidity and mortality rates; however, effective treatments for ischemic stroke-related neurological dysfunction have yet to be developed. In this study, we generated neural progenitor cells from human leukocyte antigen major loci gene-homozygous-induced pluripotent stem cells (hiPSC-NPCs) and evaluated their therapeutic effects against ischemic stroke. hiPSC-NPCs were intracerebrally transplanted into rat ischemic brains produced by transient middle cerebral artery occlusion at either the subacute or acute stage, and their in vivo survival, differentiation, and efficacy for functional improvement in neurological dysfunction were evaluated. hiPSC-NPCs were histologically identified in host brain tissues and showed neuronal differentiation into vGLUT-positive glutamatergic neurons, extended neurites into both the ipsilateral infarct and contralateral healthy hemispheres, and synaptic structures formed 12 weeks after both acute and subacute stage transplantation. They also improved neurological function when transplanted at the subacute stage with γ-secretase inhibitor pretreatment. However, their effects were modest and not significant and showed a possible risk of cells remaining in their undifferentiated and immature status in acute-stage transplantation. These results suggest that hiPSC-NPCs show cell replacement effects in ischemic stroke-damaged neural tissues, but their efficacy is insufficient for neurological functional improvement after acute or subacute transplantation. Further optimization of cell preparation methods and the timing of transplantation is required to balance the efficacy and safety of hiPSC-NPC transplantation.

AAV-Mediated Restoration of Dystrophin-Dp71 in the Brain of Dp71-Null Mice: Molecular, Cellular and Behavioral Outcomes.

A deficiency in the shortest dystrophin-gene product, Dp71, is a pivotal aggravating factor for intellectual disabilities in Duchenne muscular dystrophy (DMD). Recent advances in preclinical research have achieved some success in compensating both muscle and brain dysfunctions associated with DMD, notably using exon skipping strategies. However, this has not been studied for distal mutations in the DMD gene leading to Dp71 loss. In this study, we aimed to restore brain Dp71 expression in the Dp71-null transgenic mouse using an adeno-associated virus (AAV) administrated either by intracardiac injections at P4 (ICP4) or by bilateral intracerebroventricular (ICV) injections in adults. ICP4 delivery of the AAV9-Dp71 vector enabled the expression of 2 to 14% of brain Dp71, while ICV delivery enabled the overexpression of Dp71 in the hippocampus and cortex of adult mice, with anecdotal expression in the cerebellum. The restoration of Dp71 was mostly located in the glial endfeet that surround capillaries, and it was associated with partial localization of Dp71-associated proteins, α1-syntrophin and AQP4 water channels, suggesting proper restoration of a scaffold of proteins involved in blood-brain barrier function and water homeostasis. However, this did not result in significant improvements in behavioral disturbances displayed by Dp71-null mice. The potential and limitations of this AAV-mediated strategy are discussed. This proof-of-concept study identifies key molecular markers to estimate the efficiencies of Dp71 rescue strategies and opens new avenues for enhancing gene therapy targeting cognitive disorders associated with a subgroup of severely affected DMD patients.

Whole brain morphologic features improve the predictive accuracy of IDH status and VEGF expression levels in gliomas.

Glioma is a systemic disease that can induce micro and macro alternations of whole brain. Isocitrate dehydrogenase and vascular endothelial growth factor are proven prognostic markers and antiangiogenic therapy targets in glioma. The aim of this study was to determine the ability of whole brain morphologic features and radiomics to predict isocitrate dehydrogenase status and vascular endothelial growth factor expression levels. This study recruited 80 glioma patients with isocitrate dehydrogenase wildtype and high vascular endothelial growth factor expression levels, and 102 patients with isocitrate dehydrogenase mutation and low vascular endothelial growth factor expression levels. Virtual brain grafting, combined with Freesurfer, was used to compute morphologic features including cortical thickness, LGI, and subcortical volume in glioma patient. Radiomics features were extracted from multiregional tumor. Pycaret was used to construct the machine learning pipeline. Among the radiomics models, the whole tumor model achieved the best performance (accuracy 0.80, Area Under the Curve 0.86), while, after incorporating whole brain morphologic features, the model had a superior predictive performance (accuracy 0.82, Area Under the Curve 0.88). The features contributed most in predicting model including the right caudate volume, left middle temporal cortical thickness, first-order statistics, shape, and gray-level cooccurrence matrix. Pycaret, based on morphologic features, combined with radiomics, yielded highest accuracy in predicting isocitrate dehydrogenase mutation and vascular endothelial growth factor levels, indicating that morphologic abnormalities induced by glioma were associated with tumor biology.

Life-Threatening MOG Antibody-Associated Hemorrhagic ADEM With Elevated CSF IL-6.

Acute disseminated encephalomyelitis (ADEM) is one characteristic manifestation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). A previously healthy man presented with retro-orbital headache and urinary retention 14 days after Tdap vaccination. Brain and spine MRI suggested a CNS demyelinating process. Despite treatment with IV steroids, he deteriorated, manifesting hemiparesis and later impaired consciousness, requiring intubation. A repeat brain MRI demonstrated new bilateral supratentorial lesions associated with venous sinus thrombosis, hemorrhage, and midline shift. Anti-MOG antibody was present at a high titer. CSF IL-6 protein was >2,000 times above the upper limits of normal. He improved after plasma exchange, then began monthly treatment alone with anti-IL-6 receptor antibody, tocilizumab, and has remained stable. This case highlights how adult-onset MOGAD, like childhood ADEM, can rapidly become life-threatening. The markedly elevated CSF IL-6 observed here supports consideration for evaluating CSF cytokines more broadly in patients with acute MOGAD.

CNS autoimmune response in the MAM/pilocarpine rat model of epileptogenic cortical malformation.

The development of seizures in epilepsy syndromes associated with malformations of cortical development (MCDs) has traditionally been attributed to intrinsic cortical alterations resulting from abnormal network excitability. However, recent analyses at single-cell resolution of human brain samples from MCD patients have indicated the possible involvement of adaptive immunity in the pathogenesis of these disorders. By exploiting the MethylAzoxyMethanol (MAM)/pilocarpine (MP) rat model of drug-resistant epilepsy associated with MCD, we show here that the occurrence of status epilepticus and subsequent spontaneous recurrent seizures in the malformed, but not in the normal brain, are associated with the outbreak of a destructive autoimmune response with encephalitis-like features, involving components of both cell-mediated and humoral immune responses. The MP brain is characterized by blood-brain barrier dysfunction, marked and persisting CD8+ T cell invasion of the brain parenchyma, meningeal B cell accumulation, and complement-dependent cytotoxicity mediated by antineuronal antibodies. Furthermore, the therapeutic treatment of MP rats with the immunomodulatory drug fingolimod promotes both antiepileptogenic and neuroprotective effects. Collectively, these data show that the MP rat could serve as a translational model of epileptogenic cortical malformations associated with a central nervous system autoimmune response. This work indicates that a preexisting brain maldevelopment predisposes to a secondary autoimmune response, which acts as a precipitating factor for epilepsy and suggests immune intervention as a therapeutic option to be further explored in epileptic syndromes associated with MCDs.

Morphological and regional spontaneous functional aberrations in the brain associated with Crohn's disease: a systematic review and coordinate-based meta-analyses.

Crohn's disease is an acknowledged "brain-gut" disorder with unclear physiopathology. This study aims to identify potential neuroimaging biomarkers of Crohn's disease. Gray matter volume, cortical thickness, amplitude of low-frequency fluctuations, and regional homogeneity were selected as indices of interest and subjected to analyses using both activation likelihood estimation and seed-based d mapping with permutation of subject images. In comparison to healthy controls, Crohn's disease patients in remission exhibited decreased gray matter volume in the medial frontal gyrus and concurrently increased regional homogeneity. Furthermore, gray matter volume reduction in the medial superior frontal gyrus and anterior cingulate/paracingulate gyri, decreased regional homogeneity in the median cingulate/paracingulate gyri, superior frontal gyrus, paracentral lobule, and insula were observed. The gray matter changes of medial frontal gyrus were confirmed through both methods: decreased gray matter volume of medial frontal gyrus and medial superior frontal gyrus were identified by activation likelihood estimation and seed-based d mapping with permutation of subject images, respectively. The meta-regression analyses showed a positive correlation between regional homogeneity alterations and patient age in the supplementary motor area and a negative correlation between gray matter volume changes and patients' anxiety scores in the medial superior frontal gyrus. These anomalies may be associated with clinical manifestations including abdominal pain, psychiatric disorders, and possibly reflective of compensatory mechanisms.

A Rare Case of Abnormal Diffuse Brain Uptake on an 123I MIBG Scan in a Patient With High-Risk Neuroblastoma.

ABSTRACT: 123I-meta-iodobenzylguanidine (123I-MIBG) is extensively used for initial staging and response evaluation in children with neuroblastoma. Physiological uptake of 123I-MIBG occurs in the salivary glands, liver, adrenal gland, myocardium, bowel, and thyroid gland. 123I-MIBG cannot cross an intact blood-brain barrier. We present the rare case of a 3-year-old boy with neuroblastoma and meningeal metastases who underwent an 123I-MIBG scan for disease restaging that showed abnormal brain uptake. Abnormal MIBG uptake in the brain can occur if there is disruption of the blood-brain barrier either secondary to metastases or after damage to blood-brain barrier.

Exploring fetal brain tumor glioblastoma symptom verification with self organizing maps and vulnerability data analysis.

Brain tumor glioblastoma is a disease that is caused for a child who has abnormal cells in the brain, which is found using MRI "Magnetic Resonance Imaging" brain image using a powerful magnetic field, radio waves, and a computer to produce detailed images of the body's internal structures it is a standard diagnostic tool for a wide range of medical conditions, from detecting brain and spinal cord injuries to identifying tumors and also in evaluating joint problems. This is treatable, and by enabling the factor for happening, the factor for dissolving the dead tissues. If the brain tumor glioblastoma is untreated, the child will go to death; to avoid this, the child has to treat the brain problem using the scan of MRI images. Using the neural network, brain-related difficulties have to be resolved. It is identified to make the diagnosis of glioblastoma. This research deals with the techniques of max rationalizing and min rationalizing images, and the method of boosted division time attribute extraction has been involved in diagnosing glioblastoma. The process of maximum and min rationalization is used to recognize the Brain tumor glioblastoma in the brain images for treatment efficiency. The image segment is created for image recognition. The method of boosted division time attribute extraction is used in image recognition with the help of MRI for image extraction. The proposed boosted division time attribute extraction method helps to recognize the fetal images and find Brain tumor glioblastoma with feasible accuracy using image rationalization against the brain tumor glioblastoma diagnosis. In addition, 45% of adults are affected by the tumor, 40% of children and 5% are in death situations. To reduce this ratio, in this study, the Brain tumor glioblastoma is identified and segmented to recognize the fetal images and find the Brain tumor glioblastoma diagnosis. Then the tumor grades were analyzed using the efficient method for the imaging MRI with the diagnosis result of partially high. The accuracy of the proposed TAE-PIS system is 98.12% which is higher when compared to other methods like Genetic algorithm, Convolution neural network, fuzzy-based minimum and maximum neural network and kernel-based support vector machine respectively. Experimental results show that the proposed method archives rate of 98.12% accuracy with low response time and compared with the Genetic algorithm (GA), Convolutional Neural Network (CNN), fuzzy-based minimum and maximum neural network (Fuzzy min-max NN), and kernel-based support vector machine. Specifically, the proposed method achieves a substantial improvement of 80.82%, 82.13%, 85.61%, and 87.03% compared to GA, CNN, Fuzzy min-max NN, and kernel-based support vector machine, respectively.

Microenvironmental reorganization in brain tumors following radiotherapy and recurrence revealed by hyperplexed immunofluorescence imaging.

The tumor microenvironment plays a crucial role in determining response to treatment. This involves a series of interconnected changes in the cellular landscape, spatial organization, and extracellular matrix composition. However, assessing these alterations simultaneously is challenging from a spatial perspective, due to the limitations of current high-dimensional imaging techniques and the extent of intratumoral heterogeneity over large lesion areas. In this study, we introduce a spatial proteomic workflow termed Hyperplexed Immunofluorescence Imaging (HIFI) that overcomes these limitations. HIFI allows for the simultaneous analysis of > 45 markers in fragile tissue sections at high magnification, using a cost-effective high-throughput workflow. We integrate HIFI with machine learning feature detection, graph-based network analysis, and cluster-based neighborhood analysis to analyze the microenvironment response to radiation therapy in a preclinical model of glioblastoma, and compare this response to a mouse model of breast-to-brain metastasis. Here we show that glioblastomas undergo extensive spatial reorganization of immune cell populations and structural architecture in response to treatment, while brain metastases show no comparable reorganization. Our integrated spatial analyses reveal highly divergent responses to radiation therapy between brain tumor models, despite equivalent radiotherapy benefit.

Lycium Barbarum Polysaccharides Improves Cognitive Functions in ICV-STZ-Induced Alzheimer's Disease Mice Model by Improving the Synaptic Structural Plasticity and Regulating IRS1/PI3K/AKT Signaling Pathway.

Lycium barbarum polysaccharide (LBP) have a certain curative effect on hypoglycemic and neuroprotective effects, but the specific mechanism is unclear and needs to be further explored. This study aimed to clarify the mechanisms of LBP in the treatment of ICV-STZ mice model of AD from the perspectives of insulin resistance, IRS1/PI3K/AKT signaling pathway, and synaptic protein expression. We used male C57BL/6J mice injected with STZ (3 mg/kg) in the lateral ventricle as an AD model. After treatment with LBP, the learning and memory abilities of ICV-STZ mice were enhanced, and the pathological changes in brain tissue were alleviated. LBP can regulate the expression of proteins related to the IRS1/PI3K/AKT signaling pathway and thereby reducing Aß deposition and tau protein phosphorylation in the brain of ICV-STZ mice. In addition, LBP also can up-regulate the expression of synaptic proteins. The results indicated that LBP played a neuroprotective role by regulating the IRS1/PI3K/AKT pathway, inhibiting tau protein hyperphosphorylation and improving the expression levels of synapse-related proteins.

Angiostrongylus cantonensis induces energy imbalance and dyskinesia in mice by reducing the expression of melanin-concentrating hormone.

BACKGROUND: Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical. METHODS: We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice's energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration. RESULTS: Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex. CONCLUSIONS: Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.

[Neuropathology of Disorders Leading to Dementia].

Dementia is characterized by acquired cognitive dysfunction caused by various neurological disorders. Many neurological conditions can cause dementia, including neurodegenerative diseases, vascular disorders, infections, inflammation, demyelination, intoxication, metabolic disorders, tumors, and head trauma. Despite recent developments in biomarkers and imaging techniques, neuropathological examination is necessary for the final diagnosis. Moreover, approximately 11% of the patients with dementia have dual or triple pathological conditions. The coexistence of neurological diseases makes it difficult for neurologists to diagnose patients accurately. Degenerative diseases are characterized by neuronal loss with gliosis in distinct parts of the brain, the presence of neuronal or glial inclusions, and abnormal protein accumulation. Senile plaques and neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease. These findings are characterized by the presence of amyloid ß protein (Aß) and phosphorylated tau protein, respectively. Although vascular dementia is common, it may be difficult to identify the relationship between vascular lesions and cognitive impairment. The incidence of sporadic Aß-type cerebral amyloid angiopathy (CAA) tends to increase with age and causes dementia due to vascular dysfunction and leukoencephalopathy. Furthermore, patients with CAA can develop inflammation. Clinical neurologists should possess a neuropathological perspective for the appropriate diagnosis and management of patients with dementia.

Hemorrhagic Presentation in Primary Central Nervous System Lymphoma: A Case Study.

BACKGROUND Primary central nervous system diffuse large B-cell lymphoma (DLBCL) is an extremely aggressive brain disease that rarely affects immunocompetent non-elderly patients, particularly with hemorrhagic presentation. Brain magnetic resonance imaging (MRI) plays an important role in the diagnosis of this entity, which typically demonstrates restricted diffusion and a T2 hypointense appearance, suggesting hypercellularity. CASE REPORT A 44-year-old man came to the emergency department with a persistent and treatment-resistant bilateral frontal headache that had been bothering him for the past 3 weeks. Upon conducting a neurological assessment, the patient displayed temporal disorientation and incoherent speech, but without any observable motor deficits. A non-contrast enhanced brain computed tomography scan was carried out, revealing a hyperattenuating, space-occupying lesion and hemorrhage in the left hemisphere of the brain. Subsequently, brain MRI demonstrated hypointense signal on T2-weighted images, restricted diffusion, and homogeneous lesional contrast enhancement, suggesting a very cellular expansive lesion with hemorrhage. To establish a definitive diagnosis, a brain biopsy was undertaken, confirming the presence of DLBCL of the primary central nervous system (germinal center phenotype). CONCLUSIONS Hemorrhagic presentation of primary central nervous system DLBCL occurs very rarely, particularly in non-elderly immunocompetent patients. Brain MRI plays an important role in the diagnosis of this entity, which allows differentiation from high-grade glial or other lesions that present more frequently with hemorrhage. Therefore, it is crucial to suspect lymphoma before surgical intervention for appropriate patient management.

Antithrombin deficiency caused by SERPINC1 gene mutation in white matter lesions: A case report.

RATIONALE: White matter lesions (WMLs) are structural changes in the brain that manifest as demyelination in the central nervous system pathologically. Vasogenic WMLs are the most prevalent type, primarily associated with advanced age and cerebrovascular risk factors. Conversely, immunogenic WMLs, typified by multiple sclerosis (MS), are more frequently observed in younger patients. It is crucial to distinguish between these 2 etiologies. Furthermore, in cases where multiple individuals exhibit WMLs within 1 family, genetic testing may offer a significant diagnostic perspective. PATIENT CONCERNS: A 25-year-old male presented to the Department of Neurology with recurrent headaches. He was healthy previously and the neurological examination was negative. Brain magnetic resonance imaging (MRI) showed widespread white matter hyperintensity lesions surrounding the ventricles and subcortical regions on T2-weighted and T2 fluid-attenuated inversion recovery images, mimicking immunogenic disease-MS. DIAGNOSES: The patient was diagnosed with a patent foramen ovale, which could explain his headache syndrome. Genetic testing unveiled a previously unidentified missense mutation in the SERPINC1 gene in the patient and his father. The specific abnormal laboratory finding was a reduction in antithrombin III activity, and the decrease may serve as the underlying cause for the presence of multiple intracranial WMLs observed in both the patient and his father. INTERVENTIONS: The patient received percutaneous patent foramen ovale closure surgery and took antiplatelet drug recommended by cardiologists and was followed up for 1 month and 6 months after operation. OUTCOMES: While the lesions on MRI remain unchanging during follow-up, the patient reported a significant relief in headaches compared to the initial presentation. LESSONS: This case introduces a novel perspective on the etiology of cerebral WMLs, suggesting that hereditary antithrombin deficiency (ATD) could contribute to altered blood composition and may serve as an underlying cause in certain individuals with asymptomatic WMLs.

Multiple Ring-Enhancing Brain Lesions: Fulminant Diffuse Cerebral Toxoplasmosis or Cerebral Metastases?

ABSTRACT: In this case report, we describe a 76-year-old woman, presenting with dizziness for the past 2 months, without other focal neurological signs. A magnetic resonance imaging of the brain was ordered by her GP. The MRI demonstrated multiple ring-enhancing lesions, both supratentorial and infratentorial. Lumbar puncture showed normal findings, in particular a normal cell count and culture. Because of the radiologic appearance, initially thought to be suggestive of cerebral abscesses, antibiotics were started. However, further workup revealed a new diagnosis of a stage IV (metastatic) small cell lung carcinoma, making diffuse brain metastases more likely. The patient was transferred to oncology/pneumology, where she was started on whole-brain radiotherapy, after which systemic therapy would start. However, because of further clinical deterioration, she was admitted at the palliative ward, where she died only 3 months after the initial presentation. In this case report, we emphasize the importance of keeping a broad differential diagnosis and briefly review the various possible pathologies causing ring-enhancing lesions.

Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.