Association of Brain Arterial Elongation With Risk of Stroke and Death in Stroke-Free Individuals: Results From NOMAS.

BACKGROUND: Brain arterial dilation and elongation characterize dolichoectasia, an arteriopathy associated with risk of stroke and death. We aim to determine whether brain arterial elongation increases the risk of stroke and death independent of brain arterial diameters. METHODS: We analyzed 1210 stroke-free participants (mean age 71±9 years, 41% men, 65% Hispanic) with available time-of-flight magnetic resonance angiogram from the Northern Manhattan Study, a population-based cohort study across a multiethnic urban community. We obtained baseline middle cerebral artery M1-segment (MCA-M1) and basilar artery (BA) mean lengths and diameters using a semi-automated software. Cox proportional hazards models adjusted for brain arterial diameters and potential confounders yielded adjusted hazards ratios with 95% CIs for the primary outcomes of incident stroke and all-cause mortality, as well as secondary outcomes including noncardioembolic stroke, vascular death, and any vascular event. RESULTS: Neither MCA-M1 nor BA lengths correlated with incident stroke or all-cause mortality. Both MCA-M1 and BA larger diameters correlated with all-cause mortality (MCA-M1 aHR, 1.52 [95% CI, 1.03-2.23], BA aHR, 1.28 [95% CI, 1.02-1.61]), as well as larger MCA-M1 diameters with vascular death (aHR, 1.84 [95% CI, 1.02-3.31]). Larger MCA-M1 and BA diameters did not correlate with incident stroke. However, larger BA diameters were associated with posterior circulation noncardioembolic stroke (aHR, 2.93 [95% CI, 1.07-8.04]). There were no statistical interactions between brain arterial lengths and diameters in relation to study outcomes. CONCLUSIONS: In a multiethnic cohort of stroke-free adults, brain arterial elongation did not correlate with risk of stroke or death, nor influenced the significant association between brain arterial dilation and vascular risk.

Ipsilateral Reversible Cerebral Vasculopathy Secondary to Carotid Artery Revascularization: A Case Report.

BACKGROUND: The emergence of neurologic symptoms after carotid revascularization is not uncommon and typically caused by perioperative ischemic stroke or hyperperfusion. Postoperative vasculopathy, including reversible cerebral vasoconstriction syndrome (RCVS) is a rare complication of carotid intervention and may be an under-identified cause of neurologic deficit after revascularization. We report a case of reversible postoperative vasculopathy following carotid revascularization as well as its management. CASE PRESENTATION: A 74 year old right-handed woman presented to the emergency department with sudden onset left arm weakness and episodic shaking while hypotensive. Computed tomography angiography revealed total occlusion of her right internal carotid artery. Transcranial Doppler monitoring demonstrated active embolic events in her right middle cerebral artery raising concern for continued stump embolization. She underwent carotid revascularization with carotid endarterectomy, mechanical thrombectomy, and carotid angioplasty and initially did well postoperatively. On postoperative day 5, she developed a fixed right gaze and left hemiparesis. Computed tomography revealed new right frontal lobe and basal ganglia infarcts, and angiography showed new right internal carotid, middle cerebral, and anterior cerebral artery vasoconstriction consistent with postoperative vasculopathy. Despite treatment with pressure augmentation and vasodilator therapy, her symptoms persisted resulting in left hemiplegia at discharge. DISCUSSION: This case highlights postoperative vasculopathy (including RCVS) as a rare potential complication after carotid revascularization that should be considered in a patient with persistent acute neurologic symptoms. Information regarding incidence and predisposing risk factors is limited. Multiple diagnostic and therapeutic modalities may be necessary in the recognition and treatment of postoperative vasculopathy.

Air1 zinc knuckles 4 and 5 and a conserved IWRXY motif are critical for the function and integrity of the Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) RNA quality control complex.

In Saccharomyces cerevisiae, non-coding RNAs, including cryptic unstable transcripts (CUTs), are subject to degradation by the exosome. The Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex in S. cerevisiae is a nuclear exosome cofactor that recruits the exosome to degrade RNAs. Trf4/5 are poly(A) polymerases, Mtr4 is an RNA helicase, and Air1/2 are putative RNA-binding proteins that contain five CCHC zinc knuckles (ZnKs). One central question is how the TRAMP complex, especially the Air1/2 protein, recognizes its RNA substrates. To characterize the function of the Air1/2 protein, we used random mutagenesis of the AIR1/2 gene to identify residues critical for Air protein function. We identified air1-C178R and air2-C167R alleles encoding air1/2 mutant proteins with a substitution in the second cysteine of ZnK5. Mutagenesis of the second cysteine in AIR1/2 ZnK1-5 reveals that Air1/2 ZnK4 and -5 are critical for Air protein function in vivo. In addition, we find that the level of CUT, NEL025c, in air1 ZnK1-5 mutants is stabilized, particularly in air1 ZnK4, suggesting a role for Air1 ZnK4 in the degradation of CUTs. We also find that Air1/2 ZnK4 and -5 are critical for Trf4 interaction and that the Air1-Trf4 interaction and Air1 level are critical for TRAMP complex integrity. We identify a conserved IWRXY motif in the Air1 ZnK4-5 linker that is important for Trf4 interaction. We also find that hZCCHC7, a putative human orthologue of Air1 that contains the IWRXY motif, localizes to the nucleolus in human cells and interacts with both mammalian Trf4 orthologues, PAPD5 and PAPD7 (PAP-associated domain containing 5 and 7), suggesting that hZCCHC7 is the Air component of a human TRAMP complex.