Engineered extracellular vesicles encapsulated Bryostatin-1 as therapy for neuroinflammation

Targeted and effective drug delivery to central nervous system (CNS) lesions is a major challenge in the treatment of multiple sclerosis (MS). Extracellular vesicles (EVs) have great promise as a...

Histomorphological spectrum of central nervous system lesions in a tertiary care hospital

Background: Central nervous system (CNS) lesions show considerable geographic and racial variations with respect to the incidence and their pattern of distribution. CNS neoplasm account for 2% of all cancers. There has been a rapid increase in incidence of CNS tumors. Many non-neoplastic CNS lesions can clinically and radiologically mimic brain tumors and to differentiate them histopathological examination is necessary.Methods: This was a descriptive cross-sectional study of 30 cases, carried out from March 2020 to February 2021, in a tertiary health care hospital. The cases were diagnosed histopathologically and categorized according to the WHO 2021 classification.Results: The study included 30 cases. 3 (10%) of them were non-neoplastic while 27 (90%) were neoplastic with glioblastoma and diffuse astrocytoma being the most common. Overall, tumors of neuroepithelial tissue (60%) was the most common entity. Frontal lobe was the most commonly observed site in the neoplastic lesion. Headache was the most common presentation. Age range varied from 7 years to 66 years with the mean age of 32.7 years.Conclusions: The spectrum of neoplastic lesions were astrocytoma, glioblastoma, ependymoma, hemagioblastoma, medulloblastoma, meningioma, non-hodgkins lymphoma, oligodendroglioma, pitutary adenoma, schwannoma and non-neoplastic were A-V malformation, brain abscess, subdural empyema.

Tumefactive demyelinating CNS lesion in a 60-year-old woman with familial Mediterranean fever

SummaryWe here report on a 60-year-old woman with familial Mediterranean fever (FMF) who developed cognitive impairment 16 years after initial diagnosis. On MRI, a new extensive white matter lesion in the right frontal lobe with mild local mass effect but without contrast enhancement was detectable and classified as a tumefactive lesion. Additional MR spectroscopy showed markedly increased choline levels accompanied by a significant lactate peak, highly suggestive of a low-florid demyelinating process. Although diffuse central nervous system (CNS) lesions have been described in single FMF cases, tumefactive lesions have not been observed in FMF patients without concomitant multiple sclerosis. In summary, this case highlights rare differential diagnoses of atypical, inflammatory CNS lesions and the clinical utility of MR spectroscopy.

NIMG-61. CLINICAL UTILITY OF SOMATOSTATIN RECEPTOR PET IMAGING BIOMARKERS FOR CHARACTERIZATION OF MENINGIOMA AMONG INCIDENTAL CNS LESIONS

BACKGROUND Somatostatin receptor (SSTR) PET/CT is utilized with increasing frequency in the clinical treatment of neuroendocrine tumors. Incidental CNS lesions are commonly noted and presumed to be meningiomas, however 68Gallium (Ga-68)-DOTATATE radionuclide use lacks specificity for meningioma identification. Currently there is no established SSTR-based imaging criteria for classification of incidental CNS lesions. METHODS We retrospectively analyzed patients across clinical and radiological databases at Mayo Clinic who had undergone both Ga-68-DOTATATE PET/CT and brain MR imaging who had an incidental CNS lesion identified with clinical or radiographic prediction of meningioma. Known meningioma diagnoses prior to imaging were excluded. Imaging indication, semi-quantitative measures, and corresponding clinical history were analyzed to identify metrics impacting both the predictive and descriptive utility of SSTR-based imaging as compared to corresponding MRI prediction in incidental CNS lesions. RESULTS Among 59 patients with a CNS lesion identified on both imaging modalities, most scans were performed for a history of neuroendocrine tumor (71%). Cases with concordant lesion type prediction of meningioma between imaging modalities (N = 25) displayed a higher median SUV max and Krenning score on Ga-68-DOTATATE PET compared to cases with concordant prediction of other lesions (N=10) or discordant prediction of meningioma (N=24). Ga-68-DOTATATE was more likely to discordantly predict meningioma as compared to the corresponding patient MRI in cases with lower SUV max values. The addition of Qclear technology was significantly associated with diagnostic clarification in cases of imaging discordant tumor type prediction. Prior cranial radiation or use of a somatostatin mimetic did not affect quantitative radiographic measures in lesion characterization, and MRI-based tumor size was similar across groups. CONCLUSION The continued development of SSTR-based imaging biomarker signatures across incidental CNS lesion subtypes will further define the role of this imaging modality in the clinical diagnosis and management of presumed meningiomas.

MORPHOLOGICAL SPECTRUM OF INTRACRANIAL SPACE OCCUPYING LESION AT TERTIARY CARE HOSPITAL-A CLINICOPATHOLOGICAL STUDY

Introduction: The annual incidence of CNS tumors ranges from 10 to 17 per 1,00,000 persons for intracranial tumors, [1] the majority of these are primary tumors. An “Intra-cranial space occupying lesion” (ICSOL)is dened as a mass lesion in the cranial cavity with a diverse etiology like benign or malignant neoplasm, inammatory or parasitic lesion, hematoma, or arterio-venous malformation.[3] Many non-neoplastic CNS lesions can clinically & radiologically simulate brain tumors. In such cases, histopathological [5] examination (HPE) can be helpful in differentiating between neoplastic and non-neoplastic etiologies. Aims and Objectives: This studywas undertaken to analyse theincidence and frequency of intracranial space occupying lesions, age and sex wise distribution, associated clinical symptoms and histopathological spectrum. Intracranial space occupying lesion biopsi Materials and Methods: es of 108 cases received indepartment of pathology, B.J. Medical College, Ahmedabad, during the period of March 2021 to August 2021. All specimens were preserved in 10% formalin and allowed to x for 24 hours, parafn embedded sections of 5 microns were cut. The hematoxylin and eosin stained sections of the CNS lesions were studied. One Hundred and Eight cases of Intracranial Spac Result: e Occupying lesions were studied, of which 8 (7.4%) cases were non neoplastic with 6 (75%) being cystic lesions and 2 (25%) were cerebral abscess. The neoplastic lesions comprised of 100 (92.6%) cases, which included 99 (99%) primary and 1 (1%) metastatic lesions. The most frequent type of CNS tumor was astrocytoma and oligodendroglioma (23 cases, 23%) followed by Meningioma (18 cases, 18%), pituitary adenoma (17 cases, 17%), Ependymoma(13 cases, 13 %) and metastatic tumor (1 case, 1%). The surgical pathologist plays an importa Conclusion: nt role in accurate diagnosis of various Intra [3] Cranial Space Occupying lesions which will be of immense help for patient prognosis and treatment.

Hyperbaric Oxygen Therapy Alleviates the Autoimmune Encephalomyelitis via the Reduction of IL-17a and GM-Csf Production of Autoreactive T Cells as Well as Boosting the Immunosuppressive IL-10 in the Central Nervous System Tissue Lesions

Multiple sclerosis (MS) is a chronic autoimmune disease mainly caused by autoreactive T cells, followed by neuronal demyelination and disabling paralysis. Hyperbaric oxygen therapy (HBOT) is usually an adjunct to therapy for the treatment of neurological disorders. However, it remains still controversial whether HBOT is an effective option for the treatment of MS. Experimental autoimmune encephalomyelitis (EAE) is a well-studied mouse model investigated for the MS pathogenesis and the efficacy of the therapeutic intervention. Both encephalitogenic Th1 and Th17 are pivotal T cell subsets immunopathogenically producing several disease-initiating/modifying cytokines in the central nervous system (CNS) lesions to further exacerbate/ameliorate the progression of EAE or MS. However, it remains unclear whether HBOT modulates the context of T helper cell subsets in CNS lesions. We employed EAE in the presence of HBOT to assess whether disease amelioration is attributed to alterations of CNS-infiltrating T cell subsets. Our results demonstrated that semi-therapeutic HBOT significantly alleviated the progression of EAE, at least, via the suppression of Th17 response, the downregulation of CD4 T helper cells expressing GM-CSF or TNF-α, and the boosting of immunomodulatory IL-4 or IL-10-expressed CD4 T cells in the CNS lesions. Conclusively, HBOT attenuated EAE through the modulation of T cell responses in an earlier stage.

A Darwinian view of Behçet's disease

Behçet’s disease (BD) is a multisystem inflammatory disorder of unknown etiology, characterized by oral and genital ulceration, with other complications including eye, skin, joint, and central nervous system (CNS) lesions. Diagnosis is based on clinical findings, which may differ between patients. There is a strong genetic basis for BD; however, only a few genes have been associated with the disease across the geographical spread of BD. In this article, we discuss the history and combination of genes involved in this complex disease in relation to the geographical range and present our view that the disease has developed from a Darwinian perspective, with different gene polymorphisms that affect the same biological pathway. Moreover, these mutations individually are protective mechanisms against the disease relevant to each region, which affected both archaic and modern humans.

SURGICAL MANAGEMENT OF INTRAMEDULLARY TUBERCULOMA: A CASE REPORT AND REVIEW OF LITERATURE

Tuberculosis (TB) is a common disease of developing countries especially in immunocompromised population. Most of the Central Nervous System (CNS) lesions in tuberculosis are intracranial with the ratio of cranial and spinal lesions averaging 42:1. Medical therapy with antitubercular drugs is the mainstay of the treatment modality for a conrmed lesion. We report a case of intramedullary spinal tuberculoma managed surgically, which did not respond to the medical management with radiological expansion and clinical deterioration. Surgical excision denitely has role in management of intramedullary tuberculoma. Early surgical intervention may provide better outcome if neurological symptoms appear or lesion size increases despite on antitubercular drug therapy.

Cranial MRI abnormalities and long-term follow-up of the lesions in 770 girls with Central Precocious Puberty

Context Central precocious puberty(CPP) may arise from central nervous system(CNS) lesions in a few affected girls. Recently, the incidence of girls with CPP has increased mostly in 6-8 year-olds, in whom the necessity of magnetic resonance imaging(MRI) is debated. Objective To investigate the frequency, long-term outcome and potential predictors of CNS lesions in a large cohort of girls with CPP. Design and Method A multi-center cohort of 770 Turkish girls with CPP who had systematic cranial MRI between 2005-2017. Age at puberty onset was < 6 years in 116 and 6-8 years in 654. CNS lesions were followed until final decision(6.2±3.1years). Potential predictors of CNS lesions were evaluated by univariate analyses. Results 104/770(13.5%) girls had abnormal brain MRI. Of these, 2.8% were previously known CNS lesions, 3.8% had newly detected and causally related CNS lesions, 3.1 % were possibly related and 3.8% were incidental. Only two(0.25%) neoplastic lesions (one low grade glioma and one meningioma) were identified; neither required intervention over follow-up of 6 and 3.5 years respectively. Age at breast developmen <6 years [OR(95%CI); 2.38(1.08-5.21)] and the peak LH/FSH ratio >0.6 [OR(95%CI); 3.13 (1.02-9.68)] were significantly associated with CNS lesions. However, both patients with neoplastic lesions were >6 years old. Conclusion Although age and LH/FSH ratio are significant predictors of CNS lesions, their predictive power is weak. Thus, systematic MRI seems to be the most efficient current approach to avoid missing an occult CNS lesion in girls with CPP, despite the low likelihood of finding a lesion requiring intervention.

Leptomeningeal Metastasis in ER+HER2- Advanced Breast Cancer Patients: A Review of the Cases in a Single Institute Over a 14-year Period

Purpose: While leptomeningeal metastases (LM) from estrogen receptor-positive, HER2-negative advanced breast cancer (ER+HER2-ABC) has a poor prognosis, the details of LM ER+HER2- are unclear. We therefore retrospectively investigated patients with LM from ER+HER2-ABC.Methods: ER+HER2-ABC patients who received any therapy at Shizuoka Cancer Center between October 2002 and December 2017 were retrospectively analyzed. Patients with central nervous system (CNS) metastases were divided into three groups: brain metastasis (BM) only (B group); BM with LM (BL group); and LM only (L group).Results: Among 369 patients, 102 developed CNS metastases: 70 (68.6%), 13 (12.8%), and 19 (18.6%) in the B, BL, and L groups, respectively. The L group showed a later onset, poorer performance status, more symptoms, and more skull metastasis than the other groups. Radiotherapy as the initial treatment was introduced to 13/13 (100%) and 15/19 (78.9%) in the BL and L groups, respectively. Subsequent systemic therapy excluding best supportive care was introduced to 5/13 (38.5%) and 5/19 (26.3%) in the BL and L groups, respectively. The median overall survival (OS) from the diagnosis of CNS lesions was 295.0, 146.0, and 99.0 days in the B, BL, and L groups, respectively, and worsening of CNS lesions was the major cause of death in the BL and L groups. Multivariate analyses showed that concurrent soft tissue metastasis (hazard ratio, 4.620) and subsequent systemic therapy (hazard ratio, 0.063) were prognostic for the L group.Conclusion: Management of LM from ER+HER2-ABC remains challenging, so a multimodal approach with novel systemic therapy is warranted.