Co-registration of Intravascular Ultrasound With Angiographic Imaging for Carotid Artery Disease.

BACKGROUND: Intravascular ultrasound (IVUS) provides endoluminal views and cross-sectional images of carotid arteries but lacks overview of vascular territory provided by angiography. Co-registration of IVUS with angiographic images may provide the potential to navigate both imaging modalities in a synchronous manner. The objective of this study is to evaluate the feasibility and accuracy of co-registering both imaging modalities in the carotid vasculature of the neck. METHODS: Fourteen patients with 15 cervical carotid artery lesions underwent angiography and subsequent treatment. In each case, an IVUS catheter was advanced to the target lesion and a reference angiography sequence was acquired. This was followed by an electrocardiography-triggered fluoroscopy sequence that was initiated upon IVUS catheter pullback. IVUS data collected during pullback were registered with fluoroscopy and evaluated for error and clinical usability. RESULTS: A total of 32 landmarks were identified that demonstrated reasonable agreement during IVUS-angiography co-registration. There was a mean registration error distance of 3.36 mm (SD 2.82 mm) between targets. The longitudinal extent and severity of the disease through the target segment could be easily evaluated after co-registration. CONCLUSION: Semiautomatic tracking and co-registration of angiography and IVUS is a new technology and has the potential to increase the use of IVUS in carotid disease and to proivde the opportunity to optimize procedural outcomes.

On-demand pulsatile intracerebral delivery of carisbamate with closed-loop direct neurostimulation therapy in an electrically induced self-sustained focal-onset epilepsy rat model.

OBJECT: The authors evaluated the preclinical feasibility of acutely stabilizing an active bihemispheric limbic epileptic circuit using closed-loop direct neurostimulation therapy in tandem with "on-demand'" convection-enhanced intracerebral delivery of the antiepileptic drug (AED) carisbamate. A rat model of electrically induced self-sustained focal-onset epilepsy was employed. METHODS: A 16-contact depth-recording microelectrode was implanted bilaterally in the dentate gyrus (DG) of the hippocampus of Fischer 344 rats. The right microelectrode array included an integrated microcatheter for drug delivery at the distal tip. Bihemispheric spontaneous self-sustained limbic status epilepticus (SSLSE) was induced in freely moving rats using a 90-minute stimulation paradigm delivered to the right medial perforant white matter pathway. Immediately following SSLSE induction, closed-loop right PP stimulation therapy concurrent with on-demand nanoboluses of the AED [(14)C]-carisbamate (n = 4), or on-demand [(14)C]-carisbamate alone (n = 4), was introduced for a mean of 10 hours. In addition, 2 reference groups received either closed-loop stimulation therapy alone (n = 4) or stimulation therapy with saline vehicle only (n = 4). All animals were sacrificed after completing the specified therapy regimen. In situ [(14)C]-autoradiography was used to determine AED distribution. RESULTS: Closed-loop direct stimulation therapy delivered unilaterally in the right PP aborted ictal runs detected in either ipsi- or contralateral hippocampi. Freely moving rats receiving closed-loop direct stimulation therapy with ondemand intracerebral carisbamate delivery experienced a significant reduction in seizure frequency (p < 0.001) and minimized seizure frequency variability during the final 50% of the therapy/recording session compared with closed-loop stimulation therapy alone. CONCLUSIONS: Unilateral closed-loop direct stimulation therapy delivered to afferent hippocampal white matter pathways concurrent with on-demand ipsilateral intracerebral delivery of nano-bolused carisbamate can rapidly decrease the frequency of electrographic seizures in an active bihemispheric epileptic network. Additionally, direct pulsatile delivery of carisbamate can stabilize seizure frequency variability compared with direct stimulation therapy alone.

Chronic unlimited recording electrocorticography-guided resective epilepsy surgery: technology-enabled enhanced fidelity in seizure focus localization with improved surgical efficacy.

OBJECT: Epilepsy surgery is at the cusp of a transformation due to the convergence of advancements in multiple technologies. Emerging neuromodulatory therapies offer the promise of functionally correcting neural instability and obviating the need for resective or ablative surgery in select cases. Chronic implanted neurological monitoring technology, delivered as part of a neuromodulatory therapeutic device or as a stand-alone monitoring system, offers the potential to monitor patients chronically in their normal ambulatory setting with outpatient medication regimens. This overcomes significant temporal limitations, pharmacological perturbations, and infection risks inherent in the present technology comprising subacute percutaneous inpatient monitoring of presurgical candidates in an epilepsy monitoring unit. METHODS: As part of the pivotal study for the NeuroPace Responsive Neurostimulation (RNS) System, the authors assessed the efficacy of the RNS System to control seizures in a group of patients with medically refractory epilepsy. Prior to RNS System implantation, these patients were not candidates for further resective surgery because they had temporal lobe epilepsy with bilateral temporal sources, frontal lobe reflex epilepsy with involvement of primary motor cortex, and occipital lobe epilepsy with substantial involvement of eloquent visual cortex. Without interfering with and beyond the scope of the therapeutic aspect of the RNS System study, the authors were able to monitor seizure and epileptiform activity from chronically implanted subdural and depth electrodes in these patients, and, in doing so, they were able to more accurately localize the seizure source. In 5 of these study patients, in whom the RNS System was not effective, the notion of resective surgery was revisited and considered in light of the additional information gleaned from the chronic intracranial recordings obtained from various permutations of electrodes monitoring sources in the frontal, temporal, parietal, and occipital lobes. RESULTS: Through long-term analysis of chronic unlimited recording electrocorticography (CURE) from chronically implanted electrodes, the authors were able to further refine seizure source localization and sufficiently increase the expected likelihood of seizure control to the extent that 4 patients who had previously been considered not to be candidates for surgery did undergo resective surgery, and all have achieved seizure freedom. A fifth patient, who had a double-band heterotopia, underwent surgery but did not achieve significant seizure reduction. CONCLUSIONS: Chronic unlimited recording electrocorticography-guided resective epilepsy surgery employs new monitoring technology in a novel way, which in this small series was felt to improve seizure localization and consequently the potential efficacy of resective surgery. This suggests that the CURE modality could improve outcomes in patients who undergo resective surgery, and it may expand the set of patients in whom resective surgery may be expected to be efficacious and therefore the potential number of patients who may achieve seizure freedom. The authors report 4 cases of patients in which this technique and technology had a direct role in guiding surgery that provided seizure freedom and that suggest this new approach warrants further study to characterize its value in presurgical evaluation. Clinical trial no.: NCT00572195 (ClinicalTrials.gov).

Prospective randomized comparison of safety and efficacy of nicardipine and nitroprusside drip for control of hypertension in the neurosurgical intensive care unit.

OBJECTIVE: The calcium channel blocker nicardipine (NC) is effective for acute control of hypertension. However, efficacy and safety in neurosurgical patients have not been evaluated. We sought to compare NC with the most commonly used agent, sodium nitroprusside (SNP), in patients with subarachnoid or intracerebral hemorrhage. METHODS: We performed a prospective randomized comparison of the safety and efficacy of NC and SNP in patients with subarachnoid or intracerebral hemorrhage. We assessed the number of dose adjustments per patient day, proportion of time within set blood pressure parameters, use of additional medications for blood pressure control, clinical outcome, and drug-related complications. RESULTS: Two hundred patients were screened and 163 patients were randomized, including 89 in the SNP group and 74 in the NC group. In 107 patients, intravenous blood pressure control was started; 60 of these patients received SNP and 47 received NC. When analyzed by intent to treat, patients randomized to NC had fewer dose adjustments per day: 5.7 versus 8.8 in the nitroprusside group (P = 0.0012, Wilcoxon rank-sum test). There were fewer additional medications per day to maintain blood pressure control in the NC group: 1.4 versus 1.9 for SNP (P = 0.043, Wilcoxon rank-sum test). Blood pressure control was similar (NC, 66% of the time within parameters; SNP, 69%). "As-treated" analysis maintained the apparent advantage of NC. CONCLUSION: When used for control of hypertension in patients with subarachnoid or intracerebral hemorrhage, NC and SNP were both safe and effective, but patients on an NC drip required fewer dose adjustments and fewer additional medications.

Sodium channel auxiliary subunits.

Voltage-gated ion channels are well known for their functional roles in excitable tissues. Excitable tissues rely on voltage-gated ion channels and their auxiliary subunits to achieve concerted electrical activity in living cells. Auxiliary subunits are also known to provide functional diversity towards the transport and biogenesis properties of the principal subunits. Recent interests in pharmacological properties of these auxiliary subunits have prompted significant amounts of efforts in understanding their physiological roles. Some auxiliary subunits can potentially serve as drug targets for novel analgesics. Three families of sodium channel auxiliary subunits are described here: beta1 and beta3, beta2 and beta4, and temperature-induced paralytic E (TipE). While sodium channel beta-subunits are encoded in many animal genomes, TipE has only been found exclusively in insects. In this review, we present phylogenetic analyses, discuss potential evolutionary origins and functional data available for each of these subunits. For each family, we also correlate the functional specificity with the history of evolution for the individual auxiliary subunits.

Phylogenetic analyses of potassium channel auxiliary subunits.

Results of recent genome-sequencing projects together with advances in biochemical, molecular genetic and physiological experimentation have allowed discovery of many transport auxiliary subunits. These subunits facilitate the proper movement of substrates across cell membranes. Mutations of any of these subunits can cause catastrophic effects to the transport mechanism and cause certain genetic diseases. Auxiliary subunits of ion channels are of particular interest because of their potential to diversify the transport properties of the principal subunits. Furthermore, ion channel auxiliary subunits may function in the capacity of enhancing surface expression, allowing gating, and providing chaperone-like activities. As a result of their evolutionary histories, these proteins can be grouped exclusively by phylogenetic techniques. Many of these families are found to be restricted to a single kingdom of life while others seem to be ubiquitous. Here we report the results of systematic analyses of three families of ion channel auxiliary subunits. Some subunits contain one or more transmembrane segments while others exist only in the cytoplasm. We have also observed potential horizontal transfer across kingdoms with these auxiliary subunits. In this report, we present tabulated results of homology searches, partial multiple alignments, secondary structure analyses, and phylogenetic trees for these families.