Aplastic Internal Carotid Artery: A Potentially Catastrophic Vascular Anomaly.

Congenital absence of an internal carotid artery (ICA) is a rare vascular anomaly and occurs in less than 0.01% of the population. We report a case of aplastic internal carotid artery in a 34-year-old female. The patient presented to the emergency department with complaints of new-onset involuntary swaying-like movement of her right arm. Brain magnetic resonance imaging showed multifocal tiny areas of acute infarcts in the bilateral frontal, parietal, and left occipital lobes in the watershed distribution. There was no visualization of the flow of the intracranial left internal carotid artery. Follow-up CTA of the head and neck showed a congenital absence of the left internal carotid artery with no evidence of arterial dissection, occlusion, or aneurysm. Obstruction of the internal carotid artery has significant consequences for patients. This effect is amplified if the disruption occurs in the sole anterior blood supply to the parenchyma of the brain, as in this case. In our patient care, imaging was vital to the detection and subsequent treatment with anticoagulation to avoid further cerebral complications, and the patient will now have a better understanding of the increased lifetime risk of further events.

Progressive cavitating leukoencephalopathy associated with a homozygous POLG mutation of 264C>G (p.F88L).

Progressive cavitating leukoencephalopathy is a childhood neurodegenerative syndrome characterized by brain MR imaging findings of patchy leukoencephalopathy with cavities and vascular permeability, initially affecting the corpus callosum and centrum semiovale, and eventually coalescing into large cystic regions of white matter. We report a case of progressive cavitating leukoencephalopathy in a 2-year-old female patient presenting as intermittent motor deficits which partially resolved over several months. Whole exome sequencing revealed a homozygous c.264C>G (p.F88L) POLG variant of uncertain pathogenicity which was potentially related to this presentation. Further testing and information are needed to prove the pathogenicity of this variant, but considering other studies which report similar genotypes in association with differing phenotypes, the current case report supports a possible pathogenicity. This case could therefore represent the first reported instance of progressive cavitating leukoencephalopathy in the presence of a POLG mutation.

LANA and hnRNP A1 Regulate the Translation of LANA mRNA through G-Quadruplexes.

During the latent phase, Kaposi's sarcoma-associated herpes virus (KSHV) maintains itself inside the host by escaping the host immune surveillance mechanism through restricted protein expression. Latency-associated nuclear antigen (LANA), the most abundantly expressed protein, is essential for viral persistence, as it plays important roles in latent viral DNA replication and efficient segregation of the viral genome to the daughter cells following cell division. KSHV evades immune detection by maintaining the levels of LANA protein below a threshold required for detection by the host immune system but sufficient to maintain the viral genome. LANA achieves this by controlling its expression through regulation of its promoters and by inhibiting its presentation through interaction with the proteins of class I and class II major histocompatibility complex (MHC) pathways. In this study, we identified a mechanism of LANA expression and restricted immune recognition through formation of G-quadruplexes in LANA mRNA. We show that the formation of these stable structures in LANA mRNA inhibits its translation to control antigen presentation, which was supported by treatment of cells with TMPyP4, a G-quadruplex-stabilizing ligand. We identified heterogenous ribonucleoprotein A1 (hnRNP A1) as a G-quadruplex-unwinding helicase, which unfolds these stable secondary structures to regulate LANA translation.IMPORTANCE LANA, the most abundantly expressed protein during latency, is a multifunctional protein which is absolutely required for the persistence of KSHV in the host cell. Even though the functions of LANA in aiding pathogenesis of the virus have been extensively studied, the mechanism of how LANA escapes host's immune surveillance is not fully understood. This study sheds light on the autoregulatory role of LANA to modulate its expression and immune evasion through formation of G-quadruplexes in its mRNA. We used G-quadruplex-stabilizing ligand to define the inhibition in LANA expression and presentation on the cell surface through MHC class I. We defined the autoregulatory role of LANA and identified a cellular RNA helicase, hnRNP A1, regulating the translation of LANA mRNA. This interaction of hnRNP A1 with LANA mRNA could be exploited for controlling KSHV latency.

A Rare Case of Carotid Web Presenting with Ischemic Stroke in a Young Woman and a Brief Review of the Literature.

Carotid web is a radiological description of a shelf-like intraluminal filling defect in the carotid bulb. It is histologically defined as atypical fibromuscular dysplasia (FMD), with abnormal fibrosis and smooth muscle cell hyperplasia in the tunica intima. The spur-like intraluminal protrusion can serve as a nidus for thrombus formation, which could cause systemic embolism and ischemic strokes. We report a case of a 20-year-old female patient presenting with acute ischemic stroke in the ipsilateral middle cerebral artery (MCA) territory. We also discuss the incidence, the prevalence, the pathophysiology, the treatment, and the recurrence of carotid web based on the currently available literature.