Congenital acute myeloid leukemia with unique translocation t(11;19)(q23;p13.3)

Congenital leukemia is rarely encountered in clinical practice, even in tertiary children's hospitals. Leukemia may cause significant coagulopathy, putting the patient at risk of intracranial hemorrhage. In this case, the authors present a female infant with a unique mixed phenotypic congenital acute myeloid leukemia showing mixed-lineage leukemia (MLL) rearrangement and severe coagulopathy resulting in a large subdural hematoma. Despite the fatal outcome in this case, neurosurgical treatment of patients with acute myeloid leukemia should be considered if coagulopathy and the clinical scenario allow

Recurrent adult-onset hypophyseal Langerhans cell histiocytosis after radiotherapy: A case report

INTRODUCTION: Langerhans cell histiocytosis is a rare disease within the adult population, with very few cases reported as solitary hypophyseal lesions in adults. Of the reported cases, most have been treated successfully with surgery, radiotherapy, and/or chemotherapy. Radiotherapy has been thought to be curative at the relatively low dose of 20Gy. Here we report a case of recurrent hypophyseal Langerhans cell histiocytosis 9 months after radiotherapy with an interval period of symptomatic and radiographic response to therapy. CASE PRESENTATION: A 50-year-old Caucasian woman who had headaches, memory difficulties, and diabetes insipidus was found to have a 2.5cm suprasellar mass. Langerhans cell histiocytosis was diagnosed following stereotactic brain biopsy. Further workup revealed no other lesions. Initial radiation treatment succeeded in shrinking the tumor and relieving clinical symptoms temporarily; however, growth and recurrence of clinical symptoms was noted at 9 months. Re-irradiation was well tolerated and the patient had no acute side effects. CONCLUSION: Isolated hypophyseal involvement by Langerhans cell histiocytosis in adults is a unique presentation of a rare disease. Although radiotherapy doses as low as 20Gy have been reported to offer control, this case demonstrates that higher doses may be warranted to ensure tumor control. With modern imaging and radiotherapy techniques higher doses should offer little increased more durable risk to surrounding critical structures

Cranial Neuropathies With an Unusual Etiology

A 47 year-old-male with a previous diagnosis of multiple sclerosis presented with acute-onset right-sided ptosis for four days. The patient had contracted COVID-19 two weeks prior (diagnosed by RT-PCR), and his symptoms resolved within one week of onset. The following week, however, the patient developed right eyelid drooping and decreased vision bilaterally. Examination was notable for new right cranial nerve III, IV, and V palsies, and a left relative afferent pupillary defect. MRI brain and orbits demonstrated abnormal pachymeningeal enhancement, and enhancement of the cavernous sinus and bilateral optic nerve sheath complexes (with sparing of the optic nerves). Though these findings were found to be present eight year ago, there was noted progression

Estrogen receptor dimerization: ligand binding regulates dimer affinity and dimer dissociation rate Mol Endocrinol 16

Nuclear receptors form strong dimers that are essential for their function as transcription factors, and it is thought that ligand binding can affect dimer stability. In this report, we describe convenient fluorescence resonance energy transfer (FRET)-based methods for measuring the thermodynamic and kinetic stability of dimers of the estrogen receptor-� ligand-binding domain (ER�-LBD). We have developed receptors that are chemically labeled with a single fluorophore in a site-specific manner. These fluorophore-labeled ERs are functional and can be used to measure directly the affinity and stability of ER�-LBD dimers. Our results indicate that unliganded ER�-LBDs exist as very stable dimers and that the dissociation rate of these dimers is slow (t 1/2

A repository of grade 1 and 2 meningioma MRIs in a public dataset for radiomics reproducibility tests.

PURPOSE: Meningiomas are the most common primary brain tumors in adults with management varying widely based on World Health Organization (WHO) grade. However, there are limited datasets available for researchers to develop and validate radiomic models. The purpose of our manuscript is to report on the first dataset of meningiomas in The Cancer Imaging Archive (TCIA). ACQUISITION AND VALIDATION METHODS: The dataset consists of pre-operative MRIs from 96 patients with meningiomas who underwent resection from 2010-2019 and include axial T1post and T2-FLAIR sequences-55 grade 1 and 41 grade 2. Meningioma grade was confirmed based on the 2016 WHO Bluebook classification guideline by two neuropathologists and one neuropathology fellow. The hyperintense T1post tumor and hyperintense T2-FLAIR regions were manually contoured on both sequences and resampled to an isotropic resolution of 1 × 1 × 1 mm3 . The entire dataset was reviewed by a certified medical physicist. DATA FORMAT AND USAGE NOTES: The data was imported into TCIA for storage and can be accessed at https://doi.org/10.7937/0TKV-1A36. The total size of the dataset is 8.8GB, with 47 519 individual Digital Imaging and Communications in Medicine (DICOM) files consisting of 384 image series, and 192 structures. POTENTIAL APPLICATIONS: Grade 1 and 2 meningiomas have different treatment paradigms and are often treated based on radiologic diagnosis alone. Therefore, predicting grade prior to treatment is essential in clinical decision-making. This dataset will allow researchers to create models to auto-differentiate grade 1 and 2 meningiomas as well as evaluate for other pathologic features including mitotic index, brain invasion, and atypical features. Limitations of this study are the small sample size and inclusion of only two MRI sequences. However, there are no meningioma datasets on TCIA and limited datasets elsewhere although meningiomas are the most common intracranial tumor in adults

Detection of perillyl alcohol and its metabolite perillic acid in postsurgical glioblastoma tissue after intranasal administration of NEO100: illustrative case.

BACKGROUND: Intranasal delivery of NEO100, a pharmaceutical-grade version of the natural monoterpene perillyl alcohol (POH), is undergoing clinical phase IIa testing as a treatment for glioblastoma (GBM). However, so far there is no evidence that intranasal delivery of NEO100 indeed results in POH reaching intracranial malignancies in a patient. OBSERVATIONS: After surgical removal of her recurrent GBM tumor, a patient received daily intranasal NEO100 therapy for more than 3 years before a second recurrence emerged. At that time, a final dose of NEO100 was given shortly before the tumor tissue was surgically removed, and the tissue was processed for high-performance liquid chromatography analysis of POH and its primary metabolite, perillic acid (PA). Both molecules could readily be detected in the tumor tissue. LESSONS: This is the first demonstration of POH and PA in brain tumor tissue from any patient. It reveals that intranasal administration of NEO100 is a valid approach to achieve delivery of this agent to a brain tumor. In view of the noninvasive and safe nature of this method, along with tentative indications of activity, our findings add confidence to the notion that intranasal administration of NEO100 holds potential as a new treatment option for brain-localized malignancies

Automatic differentiation of Grade I and II meningiomas on magnetic resonance image using an asymmetric convolutional neural network

The Grade of meningioma has significant implications for selecting treatment regimens ranging from observation to surgical resection with adjuvant radiation. For most patients, meningiomas are diagnosed radiologically, and Grade is not determined unless a surgical procedure is performed. The goal of this study is to train a novel auto-classification network to determine Grade I and II meningiomas using T1-contrast enhancing (T1-CE) and T2-Fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. Ninety-six consecutive treatment naïve patients with pre-operative T1-CE and T2-FLAIR MR images and subsequent pathologically diagnosed intracranial meningiomas were evaluated. Delineation of meningiomas was completed on both MR images. A novel asymmetric 3D convolutional neural network (CNN) architecture was constructed with two encoding paths based on T1-CE and T2-FLAIR. Each path used the same 3 × 3 × 3 kernel with different filters to weigh the spatial features of each sequence separately. Final model performance was assessed by tenfold cross-validation. Of the 96 patients, 55 (57%) were pathologically classified as Grade I and 41 (43%) as Grade II meningiomas. Optimization of our model led to a filter weighting of 18:2 between the T1-CE and T2-FLAIR MR image paths. 86 (90%) patients were classified correctly, and 10 (10%) were misclassified based on their pre-operative MRs with a model sensitivity of 0.85 and specificity of 0.93. Among the misclassified, 4 were Grade I, and 6 were Grade II. The model is robust to tumor locations and sizes. A novel asymmetric CNN with two differently weighted encoding paths was developed for successful automated meningioma grade classification. Our model outperforms CNN using a single path for single or multimodal MR-based classification

347 Histopathology of Necrotic Spinal Cord Tissue Exudate Collected During Surgical Implantation of a Biodegradable Scaffold Following Acute Spinal Cord Injury: Pre-clinical and Clinical Findings

Abstract INTRODUCTION Acute implantation of biodegradable scaffolds following spinal cord injury (SCI) has been shown pre-clinically to reduce chronic cavitation, increase white matter sparing, and increase the deposition of neuropermissive remodeled tissue. The surgical procedure of scaffold implantation allows for the gentle removal of acutely necrotic tissue resulting in a cavity in which the scaffold is placed. Here we report for the first time on the histopathological findings in both animal and human tissue specimens. METHODS Pre-clinically, experimental spinal cord contusion injuries were performed as previously reported in pigs. Clinically, the ongoing INSPIRE study (NCT02138110) is currently enrolling baseline T2-T12/L1 subjects with neurologically complete (AIS A) SCI within 96 hours of injury. The surgical procedure for implantation consists of durotomy and sometimes myelotomy. Commonly, damaged spinal cord tissue under pressure spontaneously extrudes after piotomy in pure contusion injuries. This tissue sample is collected and submitted for histopathologic analysis. RESULTS >24 hours post severe contusion/compression injury in a pig model, hematoxylin and eosin-stained (H&E) paraffin sections revealed myelin and axonal degeneration along with numerous scattered spheroids (swollen axons) with hemorrhage and acute inflammation at the wound site. Surgical pathology reports document neuropil disruption and devitalization in samples collected during surgery at 40 and 82 hours post-injury. In the patient implanted at 40 hours, the tissue specimen contained fragments of disrupted neuropil with swollen and fragmented axons as evaluated by H&E and neurofilament immunohistochemistry. CONCLUSION Severe SCI leads to the rapid formation of irreversibly damaged parenchyma. Our findings in animal and human tissue samples revealed acute tissue disruption and devitalization within 24–82 hours post-injury. This time frame was too short to appreciate phagocytosis, gliosis, or axon sprouts. Future patient enrollment and tissue collection in the ongoing clinical study will continue to build upon these initial observations