Numerous pathological amyloid proteins spread from cell to cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is, therefore, key to understanding the progressive nature of such neurodegenerative diseases. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to rupture intracellular vesicles following endocytosis. We observe that the ability to induce vesicle rupture is a common feature of α-synuclein (α-syn) assemblies, as assemblies derived from WT or familial disease-associated mutant α-syn all exhibited the ability to induce vesicle rupture. Similarly, different conformational strains of WT α-syn assemblies, but not monomeric or oligomeric forms, efficiently induced vesicle rupture following endocytosis. The ability to induce vesicle rupture was not specific to α-syn, as amyloid assemblies of tau and huntingtin Exon1 with pathologic polyglutamine repeats also exhibited the ability to induce vesicle rupture. We also observe that vesicles ruptured by α-syn are positive for the autophagic marker LC3 and can accumulate and fuse into large, intracellular structures resembling Lewy bodies in vitro. Finally, we show that the same markers of vesicle rupture surround Lewy bodies in brain sections from PD patients. These data underscore the importance of this conserved endocytic vesicle rupture event as a damaging mechanism of cellular invasion by amyloid assemblies of multiple neurodegenerative disease-associated proteins, and suggest that proteinaceous inclusions such as Lewy bodies form as a consequence of continued fusion of autophagic vesicles in cells unable to degrade ruptured vesicles and their amyloid contents.

Stewart-Treves syndrome (STS) is defined as the development of cutaneous angiosarcoma in the presence of long-standing lymphedema and is a rare disease with only about 400 cases reported in world literature. We report a case of a 63-year-old morbidly obese woman with a long-standing history of lymphedema who developed angiosarcoma of the right lower extremity with metastasis and presented with acute respiratory distress. The patient underwent a thorough laboratory workup with a chest X-ray showing bilateral effusions. The hematology-oncology service was consulted and found the patient to have significant progression of angiosarcoma causing respiratory failure and cardiac instability. A decision to transition to hospice care was made and the patient eventually passed away in the intensive care unit. We present this case to raise awareness of STS in medical literature to understand its clinical manifestations better. Early detection is imperative as angiosarcoma is commonly an aggressive disease.

Chronic intestinal pseudo-obstruction (CIPO) is a rare, potentially debilitating gastrointestinal (GI) condition characterized by symptoms of intestinal obstruction with the absence of anatomic lesions. In this report, we present a case of an 86-year-old female who presented with severe abdominal discomfort, nausea, and vomiting for two weeks prior to presentation. Imaging studies revealed severe gastric distension with a lack of anatomic lesions. The patient was ultimately diagnosed with chronic idiopathic intestinal pseudo-obstruction (CIIP). The purpose of this case report is to raise awareness of this condition in the medical literature and discuss the epidemiology, pathophysiology, clinical manifestations, diagnostic workup, and treatment options of this disorder.

Swallow or deglutition syncope is an uncommon cause of syncope associated with bradyarrhythmia and hypotension during food swallowing. Early recognition of this condition is imperative but challenging. We report a case of a 60-year-old female who presented with a complaint of intermittent lightheadedness after swallowing food. An episode of presyncope was observed and a reduced pulse rate from baseline was noted when she was instructed to eat a candy bar in the clinic. Further workup revealed normal inoffice electrocardiogram, bilateral carotid ultrasound, transthoracic echocardiogram, and videofluoroscopic swallow study. Our goal in presenting this case is to raise awareness of the condition in medical literature and provide a good understanding of its clinical manifestation to prevent life-threatening events.

Renal cell carcinoma (RCC) is the most common neoplasm that arises from renal parenchyma. About onethird of patients with RCC develop metastatic spread, with common sites including the lung, liver, bone, adrenal gland, and brain. Distant metastases can be difficult to detect unless symptoms appear. We report a case of a 56-year-old female who presented to the emergency department with the unresponsiveness of unknown duration. She underwent a thorough laboratory workup, and the computed tomography (CT) scan revealed a retroperitoneal mass originating from the right kidney and a large hemorrhagic brain mass in the left frontal lobe. The patient underwent emergent full craniotomy for tumor removal, and histology confirmed metastatic RCC. Since several patients with RCC are asymptomatic, the slow growth of tumors leading to distant metastasis can be overlooked. Thus, this case demonstrates the importance of early detection of RCC to help prevent or delay further disease progression.