Vertebral Artery Dissection in a Young Adult: A Case Report.

Vertebral artery dissections (VAD) pose a significant risk for strokes, particularly in young adults. This case report details the presentation and management of a 48-year-old patient who was diagnosed with an extracranial VAD following cervical spine manipulation (CSM). The patient's symptoms included acute right-sided ataxia, giddiness, vertigo, nausea, vomiting, and persistent pain behind the right ear, prompting immediate evaluation. After ruling out acute intracerebral hemorrhages, a computed tomography angiogram (CTA) of the head and neck identified a severe narrowing of the right distal vertebral artery with a string sign at the level of the right C1 loop (V3 segment), indicating an extracranial VAD. This finding was further supported when ultrasound (US) imaging revealed a high resistance flow pattern in the right distal vertebral artery. Furthermore, T2 and diffusion-weighted magnetic resonance imaging (MRI) confirmed a 1.8 cm VAD/hematoma and a 1.4 cm acute/subacute infarct in the right posterior inferior cerebellar artery (PICA) territory. This research accentuates the importance of recognizing and addressing that neck pain can be a symptom of musculoskeletal dysfunction or could have neurovascular origins. In this case, the patient's neck pain may have been musculoskeletal or could have been due to a previous dissection. Thus, differentiation should be considered before cervical spine manipulation.

Opalski Syndrome and Elucidation of Lateral Medullary Syndrome.

In this case, a 61-year-old patient presented with Horner's syndrome of the left eye, left-sided truncal ataxia, left-sided pain/paresthesia of the face as well as right-sided loss of pain and temperature of the arms and legs. MRI findings displayed a clear 4 mm acute left lateral medullary infarct of the left posterior inferior cerebellar artery (PICA) vascular territory, indicative of lateral medullary syndrome (LMS). The presence of pre-existing medical conditions such as uncontrolled diabetes, late-stage syphilis, and a mechanical aortic valve complicated this clinical picture. The presence of ipsilateral corticospinal deficits in this patient revealed Opalski syndrome, a rare variant of LMS. This case report highlighted the importance of correlating imaging and physical examination of stroke findings.

Phosphorylation-dependent interaction of SATB1 and PIAS1 directs SUMO-regulated caspase cleavage of SATB1.

Special AT-rich sequence-binding protein 1 (SATB1) is a tissue-restricted genome organizer that provides a key link between DNA loop organization, chromatin modification/remodeling, and transcription factor association at matrix attachment regions (MARs). The SUMO E3 ligase PIAS1 enhances SUMO conjugation to SATB1 lysine-744, and this modification regulates caspase-6 mediated cleavage of SATB1 at promyelocytic leukemia nuclear bodies (PML NBs). Since this regulated caspase cleavage occurs on only a subset of SATB1, and the products are relatively stable, proteolysis likely mediates cellular processes other than programmed cell death. However, the mechanism for the spatial and temporal regulation of SATB1 sumoylation and caspase cleavage is not known. Here we report that these processes are controlled by SATB1 phosphorylation; specifically, PIAS1 interaction with SATB1 is inhibited by phosphorylation. Mutagenesis studies identified interaction of the PIAS SAP (scaffold attachment factor-A/B/acinus/PIAS) motif with SATB1 N-terminal sequences. Notably, phosphorylation of SATB1 at threonine-188 regulates its interaction with PIAS1. Sequences near this phosphorylation site, LXXLL (residues 193 to 197), appear to be conserved among a subset of SUMO substrate proteins. Thus, this motif may be commonly involved in interaction with the PIAS SAP, and phosphorylation may similarly inhibit some of these substrates by preventing their interaction with the ligase.

SUMO conjugation to the matrix attachment region-binding protein, special AT-rich sequence-binding protein-1 (SATB1), targets SATB1 to promyelocytic nuclear bodies where it undergoes caspase cleavage.

SATB1 (special AT-rich sequence-binding protein-1) provides a key link between DNA loop organization, chromatin modification/remodeling, and association of transcription factors at matrix attachment regions (MARs). To investigate the role of SATB1 in cellular events, we performed a yeast two-hybrid screen that identified SUMO-1, Ubc9, and protein inhibitor of activated STAT (PIAS) family members as SATB1 interaction partners. These proteins, working in concert, enhanced SUMO conjugation to lysine-744 of SATB1. Overexpression of SUMO or PIAS in Jurkat cells, which express high levels of endogenous SATB1, exhibited enhanced caspase cleavage of this MAR-associating protein. Sumoylation-deficient SATB1 (SATB1(K744R)) failed to display the characteristic caspase cleavage pattern; however, fusion of SUMO in-frame to SATB1(K744R) restored cleavage. A SUMO-independent interaction of inactive caspase-6 and SATB1 was noted. A subset of total cellular SATB1 localized into promyelocytic leukemia nuclear bodies where enhanced SATB1 cleavage was detected subsequent to caspase activation. These results reveal a novel sumoylation-directed caspase cleavage of this key regulatory molecule. The role of regulated proteolysis of SATB1 may be to control transcription in immune cells during normal cell functions or to assist in efficient and rapid clearance of nonfunctional or potentially damaging immune cells.