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Importance:Powassan virus is a rare but increasingly recognized cause of severe neurological disease. Objective:To highlight the diagnostic challenges and neuropathological findings in a fatal case of Powassan encephalitis caused by deer tick virus (lineage II) in a patient with follicular lymphoma receiving rituximab, with nonspecific anti-GAD65 antibodies, who was initially seen with fever and orchiepididymitis. Design, Setting, and Participants:Comparison of clinical, radiological, histological, and laboratory findings, including immunohistochemistry, real-time polymerase chain reaction, antibody detection, and unbiased sequencing assays, in a single case report (first seen in December 2016) at an academic medical center. Exposure:Infection with Powassan virus. Main Outcomes and Measures:Results of individual assays compared retrospectively. Results:In a 63-year-old man with fatal Powassan encephalitis, serum and cerebrospinal fluid IgM antibodies were not detected via standard methods, likely because of rituximab exposure. Neuropathological findings were extensive, including diffuse leptomeningeal and parenchymal lymphohistiocytic infiltration, microglial proliferation, marked neuronal loss, and white matter microinfarctions most severely involving the cerebellum, thalamus, and basal ganglia. Diagnosis was made after death by 3 independent methods, including demonstration of Powassan virus antigen in brain biopsy and autopsy tissue, detection of viral RNA in serum and cerebrospinal fluid by targeted real-time polymerase chain reaction, and detection of viral RNA in cerebrospinal fluid by unbiased sequencing. Extensive testing for other etiologies yielded negative results, including mumps virus owing to prodromal orchiepididymitis. Low-titer anti-GAD65 antibodies identified in serum, suggestive of limbic encephalitis, were not detected in cerebrospinal fluid. Conclusions and Relevance:Owing to the rarity of Powassan encephalitis, a high degree of suspicion is required to make the diagnosis, particularly in an immunocompromised patient, in whom antibody-based assays may be falsely negative. Unbiased sequencing assays have the potential to detect uncommon infectious agents and may prove useful in similar scenarios.

Central nervous system (CNS) cancers account for approximately one quarter of all pediatric tumors and are the leading cause of cancer-related death in children. More than 4,000 brain and CNS tumors are diagnosed each year in children and teens, and the incidence rate has remained stagnant in recent years. The most common malignant pediatric CNS tumors are gliomas, embryonal tumors consisting of predominately medulloblastomas, and germ cell tumors. The inaugural version of the NCCN Guidelines for Pediatric Central Nervous System Cancers focuses on the diagnosis and management of patients with pediatric diffuse high-grade gliomas. The information contained in the NCCN Guidelines is designed to help clinicians navigate the complex management of pediatric patients with diffuse high-grade gliomas. The prognosis for these highly aggressive tumors is generally poor, with 5-year survival rates of <20% despite the use of combined modality therapies of surgery, radiation therapy and systemic therapy. Recent advances in molecular profiling has expanded the use of targeted therapies in patients whose tumors harbor certain alterations. However, enrollment in a clinical trial is the preferred treatment for eligible patients.

Purpose: Establish bedside biomarkers of myosteatosis for sarcopenia and cachexia. We compared ultrasound biomarkers against MRI-based percent fat, histology, and CT-based muscle density among healthy adults and adults undergoing treatment for lung cancer., Methods: We compared ultrasound and MRI myosteatosis measures among young healthy, older healthy, and older adults with non-small cell lung cancer undergoing systemic treatment, all without significant medical concerns, in a cross-sectional pilot study. We assessed each participant's rectus femoris ultrasound-based echo intensity (EI), shear wave elastography-based shear wave speed, and MRI-based proton density fat-fraction (PDFF). We also assessed BMI, rectus femoris thickness and cross-sectional area. Rectus femoris biopsies were taken for all older adults ( n = 20) and we analyzed chest CT scans for older adults undergoing treatment ( n = 10). We determined associations between muscle assessments and BMI, and compared these assessments between groups., Results: A total of 10 young healthy adults, 10 older healthy adults, and 10 older adults undergoing treatment were recruited. PDFF was lower in young adults than in older healthy adults and older adults undergoing treatment (0.3 vs. 2.8 vs. 2.9%, respectively, p = 0.01). Young adults had significantly lower EI than older healthy adults, but not older adults undergoing treatment (48.6 vs. 81.8 vs. 75.4, p = 0.02). When comparing associations between measures, PDFF was strongly associated with EI (ρ = 0.75, p < 0.01) and moderately negatively associated with shear wave speed (ρ = -0.49, p < 0.01) but not BMI, whole leg cross-sectional area, or rectus femoris cross-sectional area. Among participants with CT scans, paraspinal muscle density was significantly associated with PDFF (ρ = -0.70, p = 0.023). Histological markers of inflammation or degradation did not differ between older adult groups., Conclusion: PDFF was sensitive to myosteatosis between young adults and both older adult groups. EI was less sensitive to myosteatosis between groups, yet EI was strongly associated with PDFF unlike BMI, which is typically used in cachexia diagnosis. Our results suggest that ultrasound measures may serve to determine myosteatosis at the bedside and are more useful diagnostically than traditional weight assessments like BMI. These results show promise of using EI, shear wave speed, and PDFF proxies of myosteatosis as diagnostic and therapeutic biomarkers of sarcopenia and cachexia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lortie, Rush, Osterbauer, Colgan, Tamada, Garlapati, Campbell, Traynor, Leal, Patel, Helgager, Lee, Reeder and Kuchnia.)