Neuropathological findings and in vivo imaging correlates of the red nucleus compared to those of the substantia nigra pars compacta in parkinsonisms.

INTRODUCTION: The substantia nigra pars compacta (SNc) is the key pathologic locus in neurodegenerative parkinsonian disorders. Recently, in vivo susceptibility MRI metrics were associated with postmortem glial cell density and tau burden in the SNc of parkinsonism subjects. This study investigated the red nucleus (RN), another iron-rich region adjacent to the SNc and a potential site of higher functionality in parkinsonisms. METHODS: In vivo MRI and postmortem data were obtained from 34 parkinsonism subjects and 3 controls. Neuron density, glial cell density, and percentages of area occupied by α-synuclein and tau were quantified using digitized midbrain slides. R2* and quantitative susceptibility mapping (QSM) metrics in the RN and SNc were derived from multi-gradient echo images. Histopathology data were compared between the RN and SNc using paired t-tests. MRI-histology associations were analyzed using partial Pearson correlations. RESULTS: The RN had greater neuron (t23 = 3.169, P = 0.004) and glial cell densities (t23 = 2.407, P = 0.025) than the SNc, whereas the SNc had greater α-synuclein (t28 = 4.614, P < 0.0001) and tau burden (t24 = 4.513, P = 0.0001). In both the RN (R2*: r = 0.47, P = 0.043; QSM: r = 0.52, P = 0.024) and SNc (R2*: r = 0.57, P = 0.01; QSM: r = 0.58, P = 0.009), MRI values were associated with glial cell density but not neuron density or α-synuclein (Ps > 0.092). QSM associated with tau burden (r = 0.49, P = 0.038) in the SNc, but not the RN. CONCLUSIONS: The RN is resilient to parkinsonian-related pathological processes compared to the SNc, and susceptibility MRI captured glial cell density in both regions. These findings help to further our understanding of the underlying pathophysiological processes in parkinsonisms.

Susceptibility Magnetic Resonance Imaging Correlates with Glial Density and Tau in the Substantia Nigra Pars Compacta.

BACKGROUND: Susceptibility magnetic resonance imaging (MRI) is sensitive to iron-related changes in the substantia nigra pars compacta (SNc), the key pathologic locus of parkinsonisms. It is unclear, however, if iron deposition in the SNc is associated with its neurodegeneration. OBJECTIVE: The objective of this study was to test whether susceptibility MRI metrics in parkinsonisms are associated with SNc neuropathologic features of dopaminergic neuron loss, gliosis, and α-synuclein and tau burden. METHODS: This retrospective study included 27 subjects with both in vivo MRI and postmortem data. Multigradient echo imaging was used to derive the apparent transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) in the SNc. Archived midbrain slides that were stained with hematoxylin and eosin, anti-α-synuclein, and anti-tau were digitized to quantify neuromelanin-positive neuron density, glial density, and the percentages of area occupied by positive α-synuclein and tau staining. MRI-histology associations were examined using Pearson correlations and regression. RESULTS: Twenty-four subjects had postmortem parkinsonism diagnoses (Lewy body disorder, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration), two had only Alzheimer's neuropathology, and one exhibited only mild atrophy. Among all subjects, both R2* and QSM were associated with glial density (r ≥ 0.67; P < 0.001) and log-transformed tau burden (r ≥ 0.53; P ≤ 0.007). Multiple linear regression identified glial density and log-transformed tau as determinants for both MRI metrics (R2 ≥ 0.580; P < 0.0001). Neither MRI metric was associated with neuron density or α-synuclein burden. CONCLUSIONS: R2* and QSM are associated with both glial density and tau burden, key neuropathologic features in the parkinsonism SNc. © 2023 International Parkinson and Movement Disorder Society.

Sellar Atypical Teratoid/Rhabdoid Tumors (AT/RT): A Systematic Review and Case Illustration.

INTRODUCTION: Atypical Teratoid/Rhabdoid tumors are rare, highly malignant tumors in adults, with a median survival of 20 months. We report a case of a sellar atypical teratoid/rhabdoid tumor in a 70-year-old female treated with intraventricular chemotherapy, followed by a systematic review of the current management of sellar AT/RTs. METHODS: A comprehensive systematic literature search was conducted on Web of Science, Scopus, and PubMed Central using the key terms "sellar" and "atypical teratoid/rhabdoid tumors", following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, including patient demographics, histology, treatments, and overall survival were extracted and analyzed. Kaplan-Meier survival curves and log-rank analysis were used to compare survival outcomes between different treatment regimens. RESULTS: Our literature search disclosed 123 publications. After prespecified exclusions, 41 patients with sellar AT/RT from 30 manuscripts were identified, and 38 were included in the final analysis. Including our patient, the median age was 44 (range: 20-70) with a substantial female predominance (94.7%). Collectively, patients who received combined chemoradiation therapy had a significantly increased overall survival compared to those who received single modality or no adjuvant therapies (median OS 27 vs. 1.25 months; p=0.0052). CONCLUSION: Atypical teratoid/rhabdoid tumor in the sellar region carries a poor prognosis. Adjuvant chemotherapy and radiation therapy were associated with significantly increased overall survival. Early consideration of neuro-oncology and radiation-oncology referral and management is likely beneficial in this patient population. Intrathecal chemotherapy is a treatment modality that requires further exploration given the limited options and current dismal prognosis of adult sellar AT/RT.

Myxopapillary Ependymoma with Anaplastic Features: A Case Series and Review of the Literature.

BACKGROUND: Myxopapillary ependymomas (MPEs) with anaplastic features are rarely reported, with only 21 cases identified to date, and long-term recurrence is rarely presented. A case series is presented to expand understanding of this disease by describing 3 unique cases, including 2 that arose from MPE after a prolonged clinical course. METHODS: A literature review was performed, and 3 cases of MPE with anaplastic features from our institution were included. RESULTS: Patient 1 was a 13-year-old boy who presented with an avidly enhancing intradural lumbar mass. On gross total resection, the tumor was found to be a solid mass with areas of myxopapillary architecture and MIB-1 (Ki-67) index of 12%. Patient 2 was a woman who initially presented at age 22 with a lumbosacral tumor that was treated with surgery and radiation. A recurrent tumor was resected at age 24. At age 50, the patient presented with a large heterogeneous exophytic mass in the sacrum extending into the presacral space and Ki-67 index of 8%. This was treated with complete resection. Patient 3 was a man who initially presented at age 35 with a lower thoracic, upper lumbar mass at L2 extending into the sacrum. Following resection and radiation, a metastatic focus followed an indolent course until causing pain at the age of 48. Ki-67 index was 16%. CONCLUSIONS: The presented cases of MPE with anaplastic features make a total of 24 cases on record in the medical literature and demonstrate 2 examples of late recurrence.

Congenital tumors of the central nervous system: an institutional review of 64 cases with emphasis on tumors with unique histologic and molecular characteristics.

Congenital brain tumors are rare accounting for 0.5%-1.9% of all pediatric brain tumors. While different criteria have been used to classify a tumor as congenital, those diagnosed prior to 6 months of age are considered to be "probably" congenital in origin. We performed an institutional review of all central nervous system (CNS) tumors (surgical and autopsy specimens from 1990 to 2019) in patients less than 6 months old. Sixty-four unique cases were identified, and these accounted for 2.0% of all CNS tumor specimens at our institution. The most common tumor types were high-grade gliomas, low-grade gliomas and medulloblastomas. Atypical teratoid rhabdoid tumors, choroid plexus tumors and germ cell tumors also accounted for a significant portion of the cohort. Seven tumors were diagnosed prenatally. The most common clinical presentation at diagnosis was increased head circumference. At the conclusion of the study, over half of the patients were alive including all patients with WHO grade I and II tumors. Ninety-two percent of cases were classifiable using the 2016 WHO system, and when available, molecular findings supported the histologic diagnoses. However, several gliomas had unusual histologic features and did not correspond to a well-defined entity. Molecular testing was essential for accurate classification of a subset of these tumors, and several high-grade gliomas exhibited fusions considered unique to infantile gliomas, including those involving the MET, ALK and NTRK genes. To our knowledge, this cohort represents the largest single-institution study of congenital CNS tumors and highlights many ways in which congenital CNS tumors are distinct from CNS tumors of older pediatric patients and adults.

A Unique Case of a High-Grade Neuroepithelial Tumor With EML4-ALK Fusion in a Five-Month-Old.

We present a unique and challenging case of a high-grade neuroepithelial tumor with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion in a five-month-old child. This tumor was difficult to classify, with glial and ependymal features, reinforcing the impact of a molecular-based diagnosis in correct classification and management. The patient had two tumor resections and underwent chemotherapy following the Head Start trial treatment regimen. The patient remains well, with no residual disease on MRI 15 months after initial resection. Further studies are needed to determine the frequency of EML4-ALK fusions in these types of tumors and to optimize therapeutic protocols for children and adults, alike, suffering from this disease.

Multimodal molecular analysis of astroblastoma enables reclassification of most cases into more specific molecular entities.

Astroblastoma is a rare and controversial glioma with variable clinical behavior. The diagnosis currently rests on histologic findings of a circumscribed glioma with astroblastomatous pseudorosettes and vascular hyalinization. Immunohistochemical studies have suggested different oncogenic drivers, such as BRAF p.V600E, but very few cases have been studied using genome-wide methodologies. Recent genomic profiling identified a subset of CNS embryonal tumors with astroblastoma-like morphology that harbored MN1 gene fusions, termed "CNS high-grade neuroepithelial tumors with MN1 alteration" (CNS-HGNET-MN1). To further characterize the genetic alterations that drive astroblastomas, we performed targeted next-generation sequencing (NGS) of 500 cancer-associated genes in a series of eight cases. We correlated these findings with break-apart fluorescence in situ hybridization (FISH) analysis of the MN1 locus and genome-wide DNA methylation profiling. Four cases showed MN1 alteration by FISH, including two pediatric cases that lacked other pathogenic alterations, and two adult cases that harbored other cancer-associated gene mutations or copy number alterations (eg, CDKN2A/B homozygous deletion, TP53, ATM and TERT promoter mutations). Three of these cases grouped with the CNS-HGNET-MN1 entity by methylation profiling. Two of four MN1 intact cases by FISH showed genetic features of either anaplastic pleomorphic xanthoastrocytoma (BRAF p.V600E mutation, CDKN2A/B homozygous deletion and TERT promoter mutation) or IDH-wildtype glioblastoma (trisomy 7, monosomy 10, CDK4 amplification and TP53, NRAS and TERT promoter mutations) and these cases had an aggressive clinical course. Two clinically indolent cases remained unclassifiable despite multimodal molecular analysis. We conclude that astroblastoma histology is not specific for any entity including CNS-HGNET-MN1, and that additional genetic characterization should be considered for astroblastomas, as a number of these tumors likely contain a methylation profile or genetic alterations that suggest classification as other tumor entities. Our heterogeneous molecular findings help to explain the clinical unpredictability of astroblastoma.

A Pediatric Tumor Found Frequently in the Adult Population: A Case of Anaplastic Astroblastoma in an Elderly Patient and Review of the Literature.

Astroblastomas are rare, potentially curable primary brain tumors which can be difficult to diagnose. We present the case of astroblastoma in a 73-year-old male, an atypical age for this tumor, more classically found in pediatric and young adult populations. Through our case and review of the literature, we note that this tumor is frequently reported in adult populations and the presentation of this tumor in the elderly is well described. This tumor is an important consideration in the differential diagnosis when managing both pediatric and adult patients of any age who present with the imaging findings characteristic of this rare tumor.

Metastatic spread of systemic neoplasms to central nervous system tumors: review of the literature and case presentation of esophageal carcinoma metastatic to meningioma.

Metastatic spread of a systemic neoplasm to a central nervous system malignancy is a rare but well-documented phenomenon. Over 100 case reports of tumor-to-tumor spread involving the central nervous system have been described since the first report in 1930. Overwhelmingly, intracranial meningioma represents the most common recipient tumor, while breast and lung are the first and second most common donor malignancies, respectively. The propensity for meningiomas to harbor metastatic lesions has been attributed to cell-to-cell adhesion molecules, favorable metabolic environment as well as hormonal and mechanical factors. We distinguish the concepts of true "tumor-to-tumor metastasis" and "tumor collision" and discuss potential non-invasive diagnostic modalities that may aid in preoperatively identifying intracranial lesions harboring distal metastasis. We present the first incidence, to our knowledge, of metastatic esophageal carcinoma spread to intracranial meningioma.
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Fulminant Infectious Aortitis With Ascending Aortic Rupture.

Infectious aortitis is associated with a high rate of acute aortic adverse events. However, the nonspecificity of symptoms and low sensitivity of blood cultures may delay early recognition of this condition. A 77-year-old man was incidentally found to have aortitis. His disease took a fulminant course and was complicated by dissection and rupture only 4 days after the diagnosis. Serial computed tomographic angiography provided valuable information about the development of aortitis into dissection and rupture. Postdissection histologic analysis revealed gram-positive cocci in the aortic wall.

Traumatic intradiploic epidermoid cyst manifest as scalp papule.

A posterior fossa intradiploic epidermoid cyst was removed from the calvarium of an otherwise healthy 34-year-old woman after work up for dizziness and blurry vision. The patient admitted to a history of a firm papule that occurred occasionally after a trauma sustained to the region years prior. The authors propose that trauma and cutaneous stigmata are potential associations with intradiploic epidermoid cysts.

Assessment of processed porcine extracellular matrix as a protective barrier in a rabbit nerve wrap model.

Nerve wrapping can improve outcomes by protecting nerves in a scarred tissue bed. Autologous tissue wraps have shown good results, but there are limitations associated with harvesting and availability. Extracellular matrix (ECM) derived from porcine small intestinal submucosa offers an attractive off-the-shelf option. This study evaluated this material as a nerve wrap. The sciatic nerves of 18 New Zealand rabbits were exposed and then wrapped, while the contralateral side served as sham control. Presence and quality of adhesions, motor conduction velocity (MCV), and histology were evaluated at 1, 2, and 6 months ( N = 6 animals per time point). The quality, extent, tenacity, and overall impression of adhesions were not different from control at any time point ( P = 0.18 to 0.99). MCV was also not statistically different from control (1 month, P = 0.35; 2 months, P = 0.20; 6 months, P = 0.83). Histology demonstrated that wrapped nerves were healthy in terms of myelination, density, and vascularity compared with controls. Vascularization and incorporation of the ECM material could be visualized at explants. All assessments supported the feasibility and safety of this material as a nerve wrap. Its ability to function as a protective barrier has strong implications for clinical use in trauma and/or recurrent compression neuropathies.

Endovascular mechanical retrieval of a terminal internal carotid artery breast tumor embolus.

The authors report the case of an acute left middle cerebral artery distribution stroke caused by a terminal internal carotid artery occlusion in a patient who underwent endovascular mechanical embolectomy. Histopathological analysis of embolic material obtained from the mechanical retriever device was diagnostic of a high-grade phyllodes breast tumor. This case represents the first instance, to our knowledge, of tumor embolus extraction via mechanical retrieval during acute ischemic stroke intervention.