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BACKGROUND: The rarity of primary central nervous system lymphoma (PCNSL) and treatment heterogeneity contributes to a lack of prognostic models for evaluating posttreatment remission. This study aimed to develop and validate radiomic-based models to predict the durable response (DR) to high-dose methotrexate (HD-MTX)-based chemotherapy in PCNSL patients. METHODS: A total of 159 patients pathologically diagnosed with PCNSL between 2011 and 2021 across two institutions were enrolled. According to the NCCN guidelines, the DR was defined as the remission lasting ≥1 year after receiving HD-MTX-based chemotherapy. For each patient, a total of 1218 radiomic features were extracted from prebiopsy T1 contrast-enhanced MR images. Multiple machine-learning algorithms were utilized for feature selection and classification to build a radiomic signature. The radiomic-clinical integrated models were developed using the random forest method. Model performance was externally validated to verify its clinical utility. RESULTS: A total of 105 PCNSL patients were enrolled after excluding 54 cases with ineligibility. The training and validation cohorts comprised 76 and 29 individuals, respectively. Among them, 65 patients achieved DR. The radiomic signature, consisting of 8 selected features, demonstrated strong predictive performance, with area under the curves of 0.994 in training cohort and 0.913 in validation cohort. This signature was independently associated with the DR in both cohorts. Both the radiomic signature and integrated models significantly outperformed the clinical models in two cohorts. Decision curve analysis underscored the clinical utility of the established models. CONCLUSIONS: This radiomic signature and integrated models have the potential to accurately predict the DR to HD-MTX-based chemotherapy in PCNSL patients, providing valuable therapeutic insights.
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Neoplasias del Sistema Nervioso Central , Imagen por Resonancia Magnética , Metotrexato , Humanos , Metotrexato/uso terapéutico , Metotrexato/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Neoplasias del Sistema Nervioso Central/patología , Imagen por Resonancia Magnética/métodos , Anciano , Linfoma/tratamiento farmacológico , Linfoma/diagnóstico por imagen , Linfoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Pronóstico , Aprendizaje Automático , Resultado del Tratamiento , Estudios Retrospectivos , RadiómicaRESUMEN
BACKGROUND AND OBJECTIVE: Due to advances in early detection and treatment options, non-central nervous system (non-CNS) cancer survivors are living longer, even those with metastatic disease. Many of these survivors will experience enduring symptoms of breast cancer, such as cancer-related cognitive impairment (CRCI). Although CRCI is bothersome and, in some cases, potentially debilitating, little research has been done to address this symptom. Thus, the overarching goal of this narrative review is to provide both an overview of the problem of CRCI and its impact and focus on the latest research aimed at addressing CRCI in non-CNS cancer survivors. METHODS: A MEDLINE database (PubMed) search was conducted for terms related to non-CNS cancer, cognition, impacts of CRCI, and interventions. The English-language articles published until April 8th, 2024, were included in the search. KEY CONTENT AND FINDINGS: CRCI includes self-reported cognitive complaints and/or impaired performance in multiple cognitive domains, including memory, processing speed, attention, and executive function. CRCI, in turn, can have a significant impact on everyday functioning, work ability, work engagement and productivity, and overall quality of life (QoL) of cancer survivors. While some researchers have examined pharmacological approaches, the vast majority of the interventional studies to date to address CRCI has focused on non-pharmacological approaches. Three of the most common non-pharmacological approaches are physical activity or exercise, mind-body approaches [e.g., mindfulness-based stress reduction (MBSR)], and cognitive rehabilitative approaches [e.g., cognitive training (CT) and cognitive behavioral therapy (CBT)]. CONCLUSIONS: Addressing the cognitive health of cancer survivors is imperative but has only recently been the focus of interventional research. More research in larger and more diverse samples of non-CNS cancer survivors is needed to identify effective ways to manage CRCI for all cancer survivors. Overall, maintaining cognitive health, especially in cancer survivors who are at increased risk for deficits, is a national health care priority that should not be ignored.
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Neonicotinoids represent over a quarter of the global pesticide market. Research on their environmental impact has revealed their adverse effect on the cognitive functions of pollinators, in particular of bees. Cognitive impairments, mostly revealed by behavioural studies, are the phenotypic expression of an alteration in the underlying neural circuits, a matter deserving greater attention. Here, we reviewed studies on the impact of field-relevant doses of neonicotinoids on the neurophysiology and neurodevelopment of bees. In particular, we focus on their olfactory system as much knowledge has been gained on the different brain areas that participate in odour processing. Recent studies have revealed the detrimental effects of neonicotinoids at multiple levels of the olfactory system, including modulation of odorant-induced activity in olfactory sensory neurons, diminished neural responses in the antennal lobe (the first olfactory processing centre) and abnormal development of the neural connectivity within the mushroom bodies (central neuropils involved in multisensory integration, learning and memory storage, among others). Given the importance of olfactory perception for multiple aspects of bee biology, the reported disruption of the olfactory circuit, which can occur even upon exposure to sublethal doses of neonicotinoids, has severe consequences at both individual and colony levels. Moreover, the effects reported for a multimodal structure such as the mushroom bodies indicate that neonicotinoids' impact translates to other sensory domains. Assessing the impact of field-relevant doses of pesticides on bee neurophysiology is crucial for understanding how neonicotinoids influence their behaviour in ecological contexts and for defining effective and sustainable agricultural practices.
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This report aims to describe the identification of porcine astrovirus 3 (PAstV3) RNA in the central nervous system (CNS) of weaned pigs with clinical signs of neurological disease associated with polioencephalomyelitis in southeastern Brazil. Three, 20 -35 days-old piglets that died after clinical manifestations of a neurological syndrome were submitted to post-mortem evaluations. Tissue samples were examined by histopathology, bacteriology, and molecular assays (RT-PCR, nested-PCR, RT-qPCR, and Sanger sequencing) to detect the primary infectious disease agents associated with neurological disease in pigs. The principal neuropathological alterations occurred in the grey matter of the spinal cord and brainstem resulting in nonsuppurative poliomyelitis and rhombencephalitis. PAstV3 RNA was detected in the CNS samples of all piglets with histopathological evidence of disease and was confirmed by nucleotide sequencing. Nucleic acids from pathogens commonly associated with neurological diseases in pigs, such as porcine teschovirus, porcine sapelovirus, porcine enterovirus G, atypical porcine pestivirus, senecavirus A, and encephalomyocarditis virus was not detected by molecular assays in the three piglets. This is the first report of PAstV3 in piglets with neurological disease and lesions consistent with polioencephalomyelitis in Brazil. This report highlights the importance of monitoring health events that could compromise pig farming productivity and animal welfare.
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INTRODUCTION: Inhibition of the enzymatic function of HDAC6 is currently being explored in clinical trials ranging from peripheral neuropathies to cancers. Advances in selective HDAC6 inhibitor discovery allowed studying highly efficacious brain penetrant and peripheral restrictive compounds for treating PNS and CNS indications. AREAS COVERED: This review explores the multifactorial role of HDAC6 in cells, the common pathological hallmarks of PNS and CNS disorders, and how HDAC6 modulates these mechanisms. Pharmacological inhibition of HDAC6 and genetic knockout/knockdown studies as a therapeutic strategy in PNS and CNS indications were analyzed. Furthermore, we describe the recent developments in HDAC6 PET tracers and their utility in CNS indications. Finally, we explore the advancements and challenges with HDAC6 inhibitor compounds, such as hydroxamic acid, fluoromethyl oxadiazoles, HDAC6 degraders, and thiol-based inhibitors. EXPERT OPINION: Based on extensive preclinical evidence, pharmacological inhibition of HDAC6 is a promising approach for treating both PNS and CNS disorders, given its involvement in neurodegeneration and aging-related cellular processes. Despite the progress in the development of selective HDAC6 inhibitors, safety concerns remain regarding their chronic administration in PNS and CNS indications, and the development of novel compound classes and modalities inhibiting HDAC6 function offer a way to mitigate some of these safety concerns.
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Objective To analyze the clinical features of 17 patients with primary angiitis of the central nervous system (PACNS) and thus facilitate the early diagnosis and treatment,reduce the recurrence and mortality,and improve the prognoses of this disease. Methods We collected the data of patients with PACNS diagnosed by brain biopsy from January 2009 to June 2023 and analyzed their clinical presentations,laboratory and imaging manifestations,electrophysiological and pathological changes,and treatment regimens and prognosis. Results The 17 patients diagnosed with PACNS via brain biopsy included one child and 16 adults.The subtyping results showed that 10,2,3,2,1,and 1 patients had tumorous,spinal cord-involved,angiography-positive,rapidly progressive,hemorrhagic,and amyloid ß-related PACNS,respectively.Eleven (64.7%) of the patients were complicated with secondary epilepsy.All the patients exhibited abnormal manifestations in head MRI,with 94.1% showing lesions with uneven enhancement around the lesions or in the leptomeninges. Magnetic resonance angiography revealed large vessel abnormalities in 3 patients,and spinal cord involvement was observed in 2 patients.Histopathological typing revealed 7 (43.7%) patients with lymphocytic vasculitis and 5 (31.2%) patients with necrotizing vasculitis.Eleven patients were treated with glucocorticoids and cyclophosphamide,which resulted in partial lesion disappearance and symptom amelioration in 6 patients upon reevaluation with head MRI after 3 months of maintenance therapy.Two,1,and 3 patients experienced rapid disease progression,death,and recurrence within 1 year,respectively.Three patients showed insensitivity to hormonotherapy and residual disabilities.Two patients received rituximab after relapse and remained clinically stable during a follow-up period of 0.5-1 year. Conclusion Tumorous PACNS was more prone to epilepsy,mainly occurring in males.The most common histopathological type was necrotizing vasculitis,which responded to hormonotherapy and had favorable outcomes.Therefore,for the young patients with epilepsy and intracranial tumorous lesions,the possibility of PACNS should be considered.Spinal cord involvement in PACNS was often located in the thoracic and cervical cords,suggesting a poorer prognosis.Electromyography commonly revealed neural conduction abnormalities in the anterior horn or roots,providing clues for differential diagnosis.For suspected spinal cord involvement,comprehensive electromyography is recommended.Rapidly progressive PACNS often presented infratentorial lesions,such as lesions in the pons and medulla,with a higher mortality rate.Hemorrhagic PACNS was rare,and a multifocal hemorrhagic lesion with enhancement in the intracranial region,particularly in young patients,should raise suspicion.For the patients with recurrent or progressive disease,rituximab is a recommended therapeutic option.
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Encéfalo , Vasculitis del Sistema Nervioso Central , Humanos , Vasculitis del Sistema Nervioso Central/diagnóstico , Vasculitis del Sistema Nervioso Central/patología , Vasculitis del Sistema Nervioso Central/tratamiento farmacológico , Adulto , Biopsia , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Pronóstico , Masculino , Niño , Femenino , Imagen por Resonancia Magnética , AdolescenteRESUMEN
ALK-positive histiocytosis is a rare histiocytic disease characterized by ALK positivity. It was first described in 2008 as a systemic disease in infants. The disease often shows positivity for CD68 and CD163 on immunohistochemistry, and genomic analysis frequently reveals KIF5B::ALK fusions. ALK-positive histiocytosis typically follows an indolent course and has a promising prognosis, with conventional treatments usually being effective. Here, we report a rare case of ALK-positive histiocytosis with exclusive involvement of the central nervous system in a 33-year-old Asian adult woman. Although cranial MRI suggested a meningioma, immunohistochemical workup showed that the ALK-positive tumor cells expressed macrophage/histiocyte markers such as CD163 and CD68. Additionally, second-generation sequencing revealed a KIF5B::ALK fusion. Our case highlights the importance of the differential diagnosis in adult central nervous system tumors, emphasizing the combination of morphology, immunophenotype, and molecular approach with ALK status evaluation to confirm a diagnosis of ALK-positive histiocytosis. This case also expands the clinicopathologic spectrum of ALK-positive histiocytosis.
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Neurological complications are observed less frequently with primary Sjögren syndrome (SS). The central nervous system (CNS) has seldom been shown to exhibit symptoms of SS, making the diagnosis of SS with neurological involvement difficult. We present a rare case scenario in which a young 23-year-old male presenting with an acute history of fever, headache, vomiting, altered sensorium, and seizures was admitted and diagnosed as a sub-acute infarct in the right frontal-parietal-temporal lobes on a computed tomography (CT) scan. Upon further examination, laboratory investigations were suggestive of viral encephalitis. The patient was treated accordingly with antiviral drugs, and the patient improved. The patient took "discharge against medical advice" after 12 days, only to return to the hospital with similar complaints within 15 days. Magnetic resonance imaging (MRI) was done, which suggested an acute evolving infarct in the right frontal and parietal lobe, and further evaluation yielded a diagnosis of SS. The patient was treated with high-dose steroids for seven days. A repeat MRI showed new acute infarcts with dilatation of the ventricular system with periventricular ooze. The patient could not be revived and succumbed after one week of steroid therapy.
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Introduction: A first psychotic episode may be related to neurological diseases, especially encephalitis of infectious or autoimmune origin. It is remarkable that an immune-mediated encephalitis triggered by a confirmed subacute bacterial meningitis is documented, and this is the case we will present. Clinical case: A 22-year-old woman with no previous medical history, immunocompetent, with three months of behavioral, affective and cognitive symptoms with subsequent compromise of sensory perception and psychosis. Examination of cerebrospinal fluid showed inflammatory signs with positive FilmArray© for Streptococcus pneumoniae. She received anti-psychotic and antibiotic treatment for 2 weeks without clinical improvement. Postencephalitic syndrome with immune-mediated psychosis was considered as a diagnosis, and immunosuppressive management with corticosteroid and plasmapheresis was initiated with complete resolution of symptoms. After one year of follow-up no neurological relapse has been identified. Discussion: Encephalitis is a neurological syndrome due to brain parenchymal damage that can result in psychiatric symptoms including psychosis and behavioral changes. Its causes are usually infectious (usually viral) or autoimmune (Anti NMDA, AMPA, LGI1 or others). A psychiatric condition in bacterial meningitis without improvement with antibiotic treatment is remarkable, its presence should suggest an immune-mediated post-infectious syndrome that may respond to the use of immunomodulators even in the absence of identification of autoimmune encephalitis-associated antibodies. No similar cases have been reported in the literature. Conclusion: Immune-mediated psychosis may be a manifestation of post-encephalitic syndrome associated with bacterial meningitis and its treatment with immunosuppressants may offer benefit in cases where the use of antipsychotics and antibiotics shows no improvement.
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BACKGROUND: This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved. METHODS: We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL. RESULTS: The most used regimen (46.8%) for GBM in patients aged ≤74 years was 'Surgery + radiotherapy concomitant with temozolomide'. This regimen's total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, 'Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy' was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month). CONCLUSIONS: Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.
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OBJECTIVE: Research into the effectiveness and applicability of deep learning, radiomics, and their integrated models based on Magnetic Resonance Imaging (MRI) for preoperative differentiation between Primary Central Nervous System Lymphoma (PCNSL) and Glioblastoma (GBM), along with an exploration of the interpretability of these models. MATERIALS AND METHODS: A retrospective analysis was performed on MRI images and clinical data from 261 patients across two medical centers. The data were split into a training set (n = 153, medical center 1) and an external test set (n = 108, medical center 2). Radiomic features were extracted using Pyradiomics to build the Radiomics Model. Deep learning networks, including the transformer-based MobileVIT Model and Convolutional Neural Networks (CNN) based ConvNeXt Model, were trained separately. By applying the "late fusion" theory, the radiomics model and deep learning model were fused to produce the optimal Max-Fusion Model. Additionally, Shapley Additive exPlanations (SHAP) and Grad-CAM were employed for interpretability analysis. RESULTS: In the external test set, the Radiomics Model achieved an Area under the receiver operating characteristic curve (AUC) of 0.86, the MobileVIT Model had an AUC of 0.91, the ConvNeXt Model demonstrated an AUC of 0.89, and the Max-Fusion Model showed an AUC of 0.92. The Delong test revealed a significant difference in AUC between the Max-Fusion Model and the Radiomics Model (P = 0.02). CONCLUSION: The Max-Fusion Model, combining different models, presents superior performance in distinguishing PCNSL and GBM, highlighting the effectiveness of model fusion for enhanced decision-making in medical applications. CLINICAL RELEVANCE STATEMENT: The preoperative non-invasive differentiation between PCNSL and GBM assists clinicians in selecting appropriate treatment regimens and clinical management strategies.
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BACKGROUND: Primary central nervous system tumors are the second most common cancer among children in high-income countries (HICs). These tumors are also the leading cause of cancer-related deaths in children in this setting. Studies from HICs report gliomas as the most common pediatric cancer. However, there is paucity of data from low- and middle-income countries as not many publications have been made in this field. METHODS: The objective was to describe the disparities in detection, treatment, and survival of children with central nervous system tumors in low-income countries (LICs) when compared with HICs, using a case series. A retrospective chart review of three children treated for medulloblastoma in Uganda was done. In addition, a review of the literature about management of pediatric central nervous system tumors in both LICs and HICs was conducted. RESULTS: There are no quantifiable results for this case series. CONCLUSION: There are notable differences in the quality of care for children with pediatric central nervous system tumors in LICs when compared with HICs. In Uganda, the challenges in management of these children include few multidisciplinary specialists, long distance from the neurosurgery centers, and difficulties in making a correct pathologic diagnosis, among others.
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BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rapidly growing malignant tumor that typically shows sensitivity to high-dose methotrexate-based chemotherapy. Rapid diagnosis and early chemotherapy are thus essential to obtain the best outcome. To accomplish this, we have performed intraoperative rapid immunohistochemistry (IHC) as an examination method for obtaining accurate diagnosis during surgery. Here, to markedly enhance the accuracy of intraoperative rapid IHC, the utility of adding intraoperative rapid examinations of cytology and flow cytometry (FCM) in addition to rapid IHC was investigated. METHODS: From April 2020 to January 2024, we performed intraoperative rapid IHC in 35 patients with intracranial lesions, including PCNSL. In the last 17 of these cases, intraoperative cytology and FCM were also performed simultaneously. We examined the utility of examination methods in determining treatment strategies for brain tumors, particularly early therapeutic intervention for PCNSL. RESULTS: Postoperative final pathological diagnoses from paraffin-embedded sections were as follows: 20 PCNSLs, 9 glioblastomas, 4 diffuse gliomas, 1 meningioma, and 1 inflammatory disorder. In all cases, results from intraoperative rapid IHC were consistent with final pathological diagnoses from paraffin-embedded sections. In two cases, results from conventional intraoperative rapid pathological diagnoses based on morphological assessments using frozen sections changed with the addition of intraoperative rapid IHC. Further, the time from surgery to initiation of chemotherapy for PCNSL was significantly reduced by adding cytology and FCM to rapid IHC alone (only rapid IHC group: 7.3 days, combination group: 1.6 days; p = 0.015). CONCLUSIONS: The combination of rapid intraoperative IHC, cytology, and FCM contributes to deciding appropriate treatment strategies and facilitating early initiation of chemotherapy for PCNSL. These examination methods may allow new therapeutic strategies for not only PCNSL, but also other brain tumors.
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BACKGROUND: Results of conventional induction chemotherapies in primary central nervous system lymphoma (PCNSL) need to be improved. Ibrutinib, a BTK inhibitor, and lenalidomide, an immunomodulatory drug, have shown promising results at relapse, supporting to further assess their individual use in combination with high-dose methotrexate-based chemotherapy. METHODS: Patients with newly diagnosed PCNSL were randomized to receive four 28-day cycles of ibrutinib or lenalidomide in combination with R-MPV (rituximab, methotrexate, procarbazine, vincristine and prednisone) in a 3 + 3 design. Responders then received a consolidation with R-Cytarabine and an intensive chemotherapy with autologous stem cell transplantation. The objective of the phase IB study was to define the recommended phase II dose (RP2D) based on the dose-limiting toxicity (DLT) occurring during the first induction cycle. RESULTS: Twenty-six patients (median age 52) were randomized. Four DLTs were observed: one grade 5 aspergillosis and pneumocystosis, one grade 4 catheter-related infection and two grade 3 increased alanine aminotransferase levels. RP2D of ibrutinib and lenalidomide were 560 mg daily (D3-14 and D17-28) and 15 mg daily (D1-21) respectively, in combination with R-MPV. In both arms, the most frequent grade ≥3 treatment-related adverse events were hepatic cytolysis, neutropenia and infections. One grade 4 Lyell's syndrome was reported at cycle 2 in the lenalidomide arm. After 4 induction cycles, the overall response rates were 76.9% and 83.3% in the lenalidomide and ibrutinib arm, respectively. CONCLUSION: Targeted induction therapies combining lenalidomide or ibrutinib with R-MPV are feasible for first-line PCNSL. The safety profile is consistent with the known safety profiles of R-MPV and both targeted therapies. The phase II part of the study is ongoing. TRIAL REGISTRATION: NCT04446962.
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Adenina , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Nervioso Central , Lenalidomida , Piperidinas , Pirazoles , Pirimidinas , Humanos , Lenalidomida/administración & dosificación , Lenalidomida/uso terapéutico , Lenalidomida/efectos adversos , Adenina/análogos & derivados , Adenina/administración & dosificación , Persona de Mediana Edad , Piperidinas/administración & dosificación , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Masculino , Femenino , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Anciano , Adulto , Pirimidinas/administración & dosificación , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Pirazoles/administración & dosificación , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Vincristina/administración & dosificación , Vincristina/uso terapéutico , Vincristina/efectos adversos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Rituximab/efectos adversos , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Prednisona/efectos adversos , Linfoma/tratamiento farmacológicoRESUMEN
BACKGROUND: Charcot-Marie-Tooth type 4C (CMT4C) is a slowly progressive, autosomal recessive, sensorimotor polyneuropathy characterized by demyelination and distinct clinical features, including cranial nerve involvement. CMT4C is associated with pathogenic mutations in the SH3TC2 gene. METHODS: A patient presenting with gait instability due to demyelinating polyneuropathy and refractory trigeminal neuralgia underwent comprehensive evaluation. Nerve conduction studies, magnetic resonance imaging (MRI) of the brain, cervical spine, and thoracic spine, lumbar puncture, and genetic test through next generation sequencing were performed. RESULTS: The genetic test found an Arg1109Stop mutation in the SH3TC2 gene, associated with demyelinating polyneuropathy and cranial neuropathy. Interestingly, brain MRI showed multiple, nonenhancing white matter hyperintensities. This is the first case of CMT4C associated with white matter lesions. CONCLUSION: Any patient with slowly progressive peripheral nervous system symptoms and disproportionally abnormal nerve conduction study findings should be tested for an inherited polyneuropathy and brain imaging for screening of possible central nervous system involvement should be performed. Further investigation is needed to elucidate the pathogenetic basis of CMT4C and a possible association with white matter lesions.
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BACKGROUND: In this study, we compare outcomes of older patients with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) undergoing autologous hematopoietic cell transplantation (autoHCT) with either thiotepa/carmustine (BCNU/Thio) or thiotepa/busulfan/cyclophosphamide (TBC) conditioning. METHODS: We used a post-publication dataset made available by the Center for International Blood and Marrow Research (CIBMTR) including patients who were ≥65 years in age with PCNSL and underwent autoHCT as consolidation with TBC or BCNU/Thio conditioning. RESULTS: Out of 147 patients; n=84 received BCNU/Thio and n=63 received TBC. The 1-year NRM in the BCNU/Thio group was 10% versus 22% in the TBC group (p=0.05) and the 2-year relapse rate was 5% versus 5%, respectively (p=1.00). The 2-year PFS in the BCNU/Thio group was 85% versus 71% in the TBC group (p=0.05) and 2-year OS was 86% vs 74% (p=0.08). In a multivariable regression model, BCNU/Thio was associated with a lower risk for NRM [Hazard Ratio (HR), 0.33, p=0.009], improved PFS (HR, 0.41, p=0.008) and OS (HR, 0.37, p=0.007), but there was no association with relapse risk. CONCLUSION: We found that in older adults with PCNSL undergoing consolidation with autoHCT, BCNU/Thio conditioning is associated with lower NRM and improved OS compared to TBC.
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Brain and central nervous system (CNS) cancers constitute a heterogeneous group of cancers with poor 5-year survival rates. We aimed to report the epidemiology of brain and CNS cancers in Asia in 2020 and their projections up to 2040 by age, sex, and country, as well as their correlation with socioeconomic status. We extracted data from the 2020 Global Cancer Observatory (GLOBOCAN). Numbers, age-standardized incidence rates (ASIRs) and mortality rates (ASMRs), 5-year prevalent cases and rates, mortality-to-incidence ratios (MIRs), and crude rates were calculated. The human development index (HDI) and current healthcare expenditure (CHE)-to-gross domestic product (GDP) ratio were included as indicators of socioeconomic status. Additionally, the numbers of new cases and deaths were predicted from 2025 to 2040 by multiplying the anticipated population during this period by age-standardized rates. In 2020, there were 166,925 new cases of brain and CNS cancers in Asia, indicating a 5-year prevalence rate of 9.40 per 100,000. We also estimated the total ASIR, ASMR, and MIR as 3.20, 2.60, and 0.83, respectively. There were significant negative correlations between HDI and MIR (correlation coefficient: - 0.538, p value < 0.001) and significant positive correlations between CHE/GDP% and ASIR (correlation coefficient: 0.388, p value: 0.010) and ASMR (correlation coefficient: 0.373, p value: 0.014). In 2040, there will be 232,000 new cases of brain and CNS cancers and 200,000 subsequent deaths in Asia. Our study revealed higher brain and CNS cancer rates in Western Asia among males and elderly individuals. These findings can aid policymakers in enhancing cancer care and suggest the consideration of risk factors in future research.
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Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Humanos , Asia/epidemiología , Neoplasias del Sistema Nervioso Central/epidemiología , Neoplasias del Sistema Nervioso Central/mortalidad , Masculino , Femenino , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/mortalidad , Incidencia , Factores Socioeconómicos , Persona de Mediana Edad , Adulto , Prevalencia , AncianoRESUMEN
The brain is essential for processing and integrating sensory signals coming from peripheral tissues. Conversely, the autonomic nervous system regulated by brain centres modulates the immune responses involved in the genesis and progression of cardiovascular diseases. Understanding the pathophysiological bases of this relationship established between the brain and immune system is relevant for advancing therapies. An additional mechanism involved in the regulation of cardiovascular function is provided by the brain-mediated control of the renin-angiotensin system. In both cases, the communication is typically bidirectional and established by afferent and sensory signals collected at the level of peripheral tissues, efferent circuits, as well as of hormones. Understanding how the brain mediates the bidirectional communication and how the immune system participates in this process is object of intense investigation. This review examines key findings that support a role for these interactions in the pathogenesis of major vascular diseases that are characterized by a consistent alteration of the immune response, such as hypertension and atherosclerosis. In addition, we provide a critical appraisal of the translational implications that these discoveries have in the clinical setting where an effective management of neuroimmune and/or neuroinflammatory state might be beneficial.
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G protein-coupled receptors (GPCRs), widely expressed in the human central nervous system (CNS), perform numerous physiological functions and play a significant role in the pathogenesis of diseases. Consequently, identifying key therapeutic GPCRs targets for CNS-related diseases is garnering immense interest in research labs and pharmaceutical companies. However, using GPCRs drugs for treating neurodegenerative diseases has limitations, including side effects and uncertain effective time frame. Recognizing the rich history of herbal treatments for neurological disorders like stroke, Alzheimer's disease (AD), and Parkinson's disease (PD), modern pharmacological research is now focusing on the understanding of the efficacy of traditional Chinese medicinal herbs and compounds in modulating GPCRs and treatment of neurodegenerative conditions. This paper will offer a comprehensive, critical review of how certain natural products and compounds target GPCRs to treat neurological diseases. Conducting an in-depth study of herbal remedies and their efficacies against CNS-related disorders through GPCRs targeting will augment our strategies for treating neurological disorders. This will not only broaden our understanding of effective therapeutic methodologies but also identify the root causes of altered GPCRs signaling in the context of pathophysiological mechanisms in neurological diseases. Moreover, it would be informative for the creation of safer and more effective GPCR-mediated drugs, thereby establishing a foundation for future treatment of various neurological diseases.