CT perfusion mean transit time maps optimally distinguish benign oligemia from true "at-risk" ischemic penumbra, but thresholds vary by postprocessing technique.

BACKGROUND AND PURPOSE: Various CTP parameters have been used to identify ischemic penumbra. The purpose of this study was to determine the optimal CTP parameter and threshold to distinguish true "at-risk" penumbra from benign oligemia in acute stroke patients without reperfusion. MATERIALS AND METHODS: Consecutive stroke patients were screened and 23 met the following criteria: 1) admission scanning within 9 hours of onset, 2) CTA confirmation of large vessel occlusion, 3) no late clinical or radiographic evidence of reperfusion, 4) no thrombolytic therapy, 5) DWI imaging within 3 hours of CTP, and 6) either CT or MR follow-up imaging. CTP was postprocessed with commercial software packages, using standard and delay-corrected deconvolution algorithms. Relative cerebral blood flow, volume, and mean transit time (rCBF, rCBV and rMTT) values were obtained by normalization to the uninvolved hemisphere. The admission DWI and final infarct were transposed onto the CTP maps and receiver operating characteristic curve analysis was performed to determine optimal thresholds for each perfusion parameter in defining penumbra destined to infarct. RESULTS: Relative and absolute MTT identified penumbra destined to infarct more accurately than CBF or CBV*CBF (P < .01). Absolute and relative MTT thresholds for defining penumbra were 12s and 249% for the standard and 13.5s and 150% for the delay-corrected algorithms, respectively. CONCLUSIONS: Appropriately thresholded absolute and relative MTT-CTP maps optimally distinguish "at-risk" penumbra from benign oligemia in acute stroke patients with large-vessel occlusion and no reperfusion. The precise threshold values may vary, however, depending on the postprocessing technique used for CTP map construction.

Selective brain cooling with endovascular intracarotid infusion of cold saline: a pilot feasibility study.

BACKGROUND AND PURPOSE: Endovascular brain cooling as a method for rapid and selective induction of hypothermic neuroprotection has not been systematically studied in humans. In this clinical pilot study we investigated the feasibility, safety, and physiologic responses of short-term brain cooling with IC-CSI. MATERIALS AND METHODS: We studied 18 patients (50 +/- 10 years old, 9 women) undergoing follow-up cerebral angiography after previous treatment of vascular malformations. Isotonic saline (4-17 degrees C) was infused into 1 internal carotid artery at 33 mL/min for 10 minutes. Brain (JVB) and bladder/esophageal temperature measurements (n = 9) were performed. Both MCAs were monitored with transcranial Doppler sonography (n = 13). Arterial and JV blood were sampled to estimate hemodilution and brain oxygen extraction. RESULTS: JVB temperature dropped approximately 0.84 +/- 0.13 degrees C and systemic temperature by 0.15 +/- 0.08 degrees C from baseline (JVB versus systemic temperature: P = .0006). Systolic MCA-flow velocities decreased from 101 +/- 27 to 73 +/- 18 cm/s on the infused side and from 83 +/- 24 to 78 +/- 21 cm/s on the contralateral side (relative changes, -26 +/- 8% versus -4 +/- 27%; P = .009). Changes in hematocrit (-1.2 +/- 1.1%) and cerebral arteriovenous oxygen difference (0.2 +/- 1.0 mL O(2)/100 mL) were not significant. Doppler data showed no signs of vascular spasm or microemboli. No focal neurologic deficits occurred. Pain was not reported. CONCLUSIONS: The results of this pilot study suggest that brain cooling can be achieved safely, rapidly, and selectively by means of IC-CSI, opening a new potential avenue for acute neuroprotection. Clinical investigations with control of infusion parameters and measurements of CBF, oxygen consumption, and brain temperature are warranted.

Theoretic basis and technical implementations of CT perfusion in acute ischemic stroke, part 2: technical implementations.

CT perfusion (CTP) is a functional imaging technique that provides important information about capillary-level hemodynamics of the brain parenchyma and is a natural complement to the strengths of unenhanced CT and CT angiography in the evaluation of acute stroke, vasospasm, and other neurovascular disorders. CTP is critical in determining the extent of irreversibly infarcted brain tissue (infarct "core") and the severely ischemic but potentially salvageable tissue ("penumbra"). This is achieved by generating parametric maps of cerebral blood flow, cerebral blood volume, and mean transit time.

Theoretic basis and technical implementations of CT perfusion in acute ischemic stroke, part 1: Theoretic basis.

CT perfusion (CTP) is a functional imaging technique that provides important information about capillary-level hemodynamics of the brain parenchyma and is a natural complement to the strengths of unenhanced CT and CT angiography in the evaluation of acute stroke, vasospasm, and other neurovascular disorders. CTP is critical in determining the extent of irreversibly infarcted brain tissue (infarct "core") and the severely ischemic but potentially salvageable tissue ("penumbra"). This is achieved by generating parametric maps of cerebral blood flow, cerebral blood volume, and mean transit time.

Aortic dissection associated with a neurointerventional guidewire retained in a perforating branch of the right posterior cerebral artery.

We report a case of a 55-year-old man with a 6.5 mm right posterior cerebral artery (PCA) aneurysm. Upon attempted Guglielmi detachable coil embolisation, the guidewire was lodged in a perforating branch of the right PCA and attempted retractions were unsuccessful. The retained guidewire was left in the patient. The patient died 10 weeks later due to a perforation that dissected through the wall of the ascending aorta resulting in haemopericardium.

Sulfonylurea receptors inhibit the epithelial sodium channel (ENaC) by reducing surface expression.

In the kidney the epithelial Na+ channel (ENaC) is co-expressed with the sulfonylurea receptor (SUR), an ABC protein that shares a high degree of homology with the cystic fibrosis transmembrane conductance regulator (CFTR) and reportedly modifies ENaC in various preparations. To investigate a possible regulatory relationship between SUR and ENaC, we performed co-expression studies on Xenopus laevis oocytes, which were assayed for amiloride-sensitive currents (DeltaIami). Moreover, a chemiluminescence assay was used to investigate the surface expression of extracellular hemagglutinin-tagged SUR1 (SUR1-HA) or HA-tagged ENaC (ENaC-HA). In oocytes co-injected with SUR1/ENaC (or SUR2B/ENaC) DeltaIami was reduced by congruent with 53% (or congruent with 45%) compared to DeltaIami measured in matched control oocytes injected with ENaC alone. The inhibitory effect of SUR on DeltaIami was preserved in oocytes expressing ENaC with C-terminally truncated subunits. Co-expression of SURs did not confer sensitivity of DeltaIami to diazoxide, pinacidil, tolbutamide, or glibenclamide. ENaC does not facilitate the surface expression of SUR1-HA, which is known to be retained in the endoplasmatic reticulum (ER) by an ER-retention/retrieval signal. SUR1-HAAAA, a mutant that lacks this signal, still inhibits ENaC currents. Chemiluminescence was reduced by congruent with 49% in oocytes co-expressing ENaC-HA/SUR1 compared to that in control oocytes expressing ENaC-HA alone. We conclude that SUR does not interact with ENaC at the level of the plasma membrane but that it inhibits DeltaIami by reducing surface expression of the channel.

Conservation of pH sensitivity in the epithelial sodium channel (ENaC) with Liddle's syndrome mutation.

Gain-of-function mutations of the epithelial Na+ channel (ENaC) cause a rare form of hereditary hypertension, Liddle's syndrome. How these mutations lead to increased channel activity is not yet fully understood. Since wild-type ENaC (wt-ENaC) is highly pH-sensitive, we wondered whether an altered pH-sensitivity of ENaC might contribute to the hyperactivity of ENaC with Liddle's syndrome mutation (Liddle-ENaC). Using Xenopus laevis oocytes as an expression system, we compared the pH-sensitivity of wt-ENaC (alphabetagammarENaC) and Liddle-ENaC (alphabeta(R564stop)gammarENaC). Oocytes were assayed for an amiloride-sensitive (2 microM) inward current (deltaIami) at -60 mV holding potential and cytosolic pH was altered by changing the extracellular pH in the presence of 60 mM sodium acetate. Alternatively, cytosolic acidification was achieved by proton loading the cells using a proton-coupled oligopeptide transporter (PepT-1) co-expressed in the oocytes together with ENaC. Cytosolic but not extracellular acidification substantially reduced deltaIami while cytosolic alkalinisation had a stimulatory effect. This pH-sensitivity was largely preserved in oocytes expressing Liddle-ENaC. The inhibition of wt-ENaC and Liddle-ENaC by cytosolic acidification was independent of so-called sodium-feedback inhibition, since it was not associated with a concomitant increase in intracellular Na+ concentration estimated from the reversal potential of deltaIami. In addition C-terminal deletions in the alpha or gamma subunits or in all three subunits of ENaC did not abolish the inhibitory effect of cytosolic acidification. We conclude that ENaC's pH-sensitivity is not mediated by its cytoplasmic C-termini and that an altered pH-sensitivity of ENaC does not contribute to the pathophysiology of Liddle's syndrome.