Description: Background and Purpose— Distinguishing between symptoms of posterior circulation infarction (PCI) and anterior circulation infarction (ACI) can be challenging. This study evaluated the frequency of symptoms/signs in the 2 vascular territories to determine the diagnostic value of particular symptoms/signs for PCI. Methods— Neurological deficits were reviewed and compared from 1174 consecutive patients with a diagnosis of PCI or ACI confirmed by magnetic resonance imaging in the Chengdu Stroke Registry. The diagnostic value of specific symptoms/signs for PCI was determined by measuring their sensitivity, specificity, positive predictive value (PPV), and the OR. Results— Homolateral hemiplegia (PCI, 53.6% versus ACI, 74.9%; P 〈0.001), central facial/lingual palsy (PCI, 40.7% versus ACI, 62.2%; P 〈0.001), and hemisensory deficits (PCI, 36.4% versus ACI, 34.2%; P =0.479) were the 3 most common symptoms/signs in PCI and ACI. The signs with the highest predictive values favoring a diagnosis of PCI were Horner's syndrome (4.0% versus 0%; P 〈0.001; PPV=100.0%; OR=4.00), crossed sensory deficits (3.0% versus 0%; P 〈0.001; PPV=100.0%; OR=3.98), quadrantanopia (1.3% versus 0%; P 〈0.001; PPV=100.0%; OR=3.93), oculomotor nerve palsy (4.0% versus 0%; P 〈0.001; PPV=100.0%; OR=4.00), and crossed motor deficits (4.0% versus 0.1%; P 〈0.001; PPV=92.3%; OR=36.04); however, all had a very low sensitivity, ranging from 1.3% to 4.0%. Conclusions— This study indicates that the symptoms/signs considered typical of PCI occur far less often than was expected. Inaccurate localization would occur commonly if clinicians relied on the clinical neurological deficits alone to differentiate PCI from ACI. Neuroimaging is vital to ensure accurate localization of cerebral infarction.

Description: Background and Purpose— WNK kinases, including WNK3, and the associated downstream Ste20/SPS1-related proline-alanine–rich protein kinase (SPAK) and oxidative stress responsive 1 (OSR1) kinases, comprise an important signaling cascade that regulates the cation-chloride cotransporters. Ischemia-induced stimulation of the bumetanide-sensitive Na + -K + -Cl – cotransporter (NKCC1) plays an important role in the pathophysiology of experimental stroke, but the mechanism of its regulation in this context is unknown. Here, we investigated the WNK3-SPAK/OSR1 pathway as a regulator of NKCC1 stimulation and their collective role in ischemic brain damage. Method— Wild-type WNK3 and WNK3 knockout mice were subjected to ischemic stroke via transient middle cerebral artery occlusion. Infarct volume, brain edema, blood brain barrier damage, white matter demyelination, and neurological deficits were assessed. Total and phosphorylated forms of WNK3 and SPAK/OSR1 were assayed by immunoblotting and immunostaining. In vitro ischemia studies in cultured neurons and immature oligodendrocytes were conducted using the oxygen-glucose deprivation/reoxygenation method. Results— WNK3 knockout mice exhibited significantly decreased infarct volume and axonal demyelination, less cerebral edema, and accelerated neurobehavioral recovery compared with WNK3 wild-type mice subjected to middle cerebral artery occlusion. The neuroprotective phenotypes conferred by WNK3 knockout were associated with a decrease in stimulatory hyperphosphorylations of the SPAK/OSR1 catalytic T-loop and of NKCC1 stimulatory sites Thr 203 /Thr 207 /Thr 212 , as well as with decreased cell surface expression of NKCC1. Genetic inhibition of WNK3 or small interfering RNA knockdown of SPAK/OSR1 increased the tolerance of cultured primary neurons and oligodendrocytes to in vitro ischemia. Conclusions— These data identify a novel role for the WNK3-SPAK/OSR1-NKCC1 signaling pathway in ischemic neuroglial injury and suggest the WNK3-SPAK/OSR1 kinase pathway as a therapeutic target for neuroprotection after ischemic stroke.

Description: Background and Purpose— Whether totaled health risks in vascular events (THRIVE) score can be used to predict clinical outcomes and risk of hemorrhagic transformation in patients with special subtypes of ischemic stroke remains an open question. Methods— We analyzed the possible relationships between THRIVE score and clinical outcomes in patients with cardioembolic stroke or noncardioembolic stroke who did not receive thrombolytic therapy. Clinical outcomes and hemorrhagic transformation within 3 months of admission were compared among 3 patient subgroups with initial THRIVE scores of 0 to 2, 3 to 5, or 6 to 9. Results— A total of 505 patients with cardioembolic stroke and 3374 patients with noncardioembolic stroke were included in our analysis. As THRIVE score increased, the rate of patients showing good clinical outcome decreased, whereas the rate of mortality and hemorrhagic transformation increased after ischemic stroke. Increasing THRIVE score was independently associated with decreasing likelihood of good outcome, defined as a modified Rankin Scale score of 0 to 2 (cardioembolic stroke: odds ratio, 0.59; 95% confidence interval, 0.51–0.67; noncardioembolic stroke: odds ratio, 0.53; 95% confidence interval, 0.49–0.57), and with increasing likelihood of death (cardioembolic: odds ratio, 1.48; 95% confidence interval, 1.28–1.70; noncardioembolic: odds ratio, 1.95; 95% confidence interval, 1.76–2.16). THRIVE score showed good receiver operating characteristics for predicting good outcome and mortality in patients with cardioembolic stroke and noncardioembolic stroke. Conclusions— The THRIVE score is a simple tool that helps clinicians estimate good outcome and death after ischemic stroke.