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Shawn M. Vuong, Christopher P. Carroll, Ryan D. Tackla, William J. Jeong, and Andrew J. Ringer

During the past 20 years, the traditional supportive treatment for stroke has been radically transformed by advances in catheter technologies and a cohort of prominent randomized controlled trials that unequivocally demonstrated significant improvement in stroke outcomes with timely endovascular intervention. However, substantial limitations to treatment remain, among the most important being timely access to care. Nonetheless, stroke care has continued its evolution by incorporating technological advances from various fields that can further reduce patients' morbidity and mortality. In this paper the authors discuss the importance of emerging technologies—mobile stroke treatment units, telemedicine, and robotically assisted angiography—as future tools for expanding access to the diagnosis and treatment of acute ischemic stroke.

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A. Scott Emmert, Shawn M. Vuong, Crystal Shula, Diana Lindquist, Weihong Yuan, Yueh-Chiang Hu, Francesco T. Mangano, and June Goto

OBJECTIVE

Emergence of CRISPR/Cas9 genome editing provides a robust method for gene targeting in a variety of cell types, including fertilized rat embryos. The authors used this method to generate a transgenic rat L1cam knockout model of X-linked hydrocephalus (XLH) with human genetic etiology. The object of this study was to use diffusion tensor imaging (DTI) in studying perivascular white matter tract injury in the rat model and to characterize its pathological definition in histology.

METHODS

Two guide RNAs designed to disrupt exon 4 of the L1cam gene on the X chromosome were injected into Sprague-Dawley rat embryos. Following embryo transfer into pseudopregnant females, rats were born and their DNA was sequenced for evidence of L1cam mutation. The mutant and control wild-type rats were monitored for growth and hydrocephalus phenotypes. Their macro- and microbrain structures were studied with T2-weighted MRI, DTI, immunohistochemistry, and transmission electron microscopy (TEM).

RESULTS

The authors successfully obtained 2 independent L1cam knockout alleles and 1 missense mutant allele. Hemizygous male mutants from all 3 alleles developed hydrocephalus and delayed development. Significant reductions in fractional anisotropy and axial diffusivity were observed in the corpus callosum, external capsule, and internal capsule at 3 months of age. The mutant rats did not show reactive gliosis by then but exhibited hypomyelination and increased extracellular fluid in the corpus callosum.

CONCLUSIONS

The CRISPR/Cas9-mediated genome editing system can be harnessed to efficiently disrupt the L1cam gene in rats for creation of a larger XLH animal model than previously available. This study provides evidence that the early pathology of the periventricular white matter tracts in hydrocephalus can be detected in DTI. Furthermore, TEM-based morphometric analysis of the corpus callosum elucidates the underlying cytopathological changes accompanying hydrocephalus-derived variations in DTI. The CRISPR/Cas9 system offers opportunities to explore novel surgical and imaging techniques on larger mammalian models.

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Joseph C. Serrone, Ryan D. Tackla, Yair M. Gozal, Dennis J. Hanseman, Steven L. Gogela, Shawn M. Vuong, Jennifer A. Kosty, Calen A. Steiner, Bryan M. Krueger, Aaron W. Grossman, and Andrew J. Ringer

OBJECTIVE

Many low-risk unruptured intracranial aneurysms (UIAs) are followed for growth with surveillance imaging. Growth of UIAs likely increases the risk of rupture. The incidence and risk factors of UIA growth or de novo aneurysm formation require further research. The authors retrospectively identify risk factors and annual risk for UIA growth or de novo aneurysm formation in an aneurysm surveillance protocol.

METHODS

Over an 11.5-year period, the authors recommended surveillance imaging to 192 patients with 234 UIAs. The incidence of UIA growth and de novo aneurysm formation was assessed. With logistic regression, risk factors for UIA growth or de novo aneurysm formation and patient compliance with the surveillance protocol was assessed.

RESULTS

During 621 patient-years of follow-up, the incidence of aneurysm growth or de novo aneurysm formation was 5.0%/patient-year. At the 6-month examination, 5.2% of patients had aneurysm growth and 4.3% of aneurysms had grown. Four de novo aneurysms formed (0.64%/patient-year). Over 793 aneurysm-years of follow-up, the annual risk of aneurysm growth was 3.7%. Only initial aneurysm size predicted aneurysm growth (UIA < 5 mm = 1.6% vs UIA ≥ 5 mm = 8.7%, p = 0.002). Patients with growing UIAs were more likely to also have de novo aneurysms (p = 0.01). Patient compliance with this protocol was 65%, with younger age predictive of better compliance (p = 0.01).

CONCLUSIONS

Observation of low-risk UIAs with surveillance imaging can be implemented safely with good adherence. Aneurysm size is the only predictor of future growth. More frequent (semiannual) surveillance imaging for newly diagnosed UIAs and UIAs ≥ 5 mm is warranted.