Stenting as a treatment for cranio-cervical artery dissection: Improved major adverse cardiovascular event-free survival.

INTRODUCTION: Cranio-cervical artery dissection (CeAD) is a common cause of cerebrovascular events in young subjects with no clear treatment strategy established. We evaluated the incidence of major adverse cardiovascular events (MACE) in CeAD patients treated with and without stent placement. METHODS: COMParative effectiveness of treatment options in cervical Artery diSSection (COMPASS) is a single high-volume center observational, retrospective longitudinal registry that enrolled consecutive CeAD patients over a 2-year period. Patients were ≥ 18 years of age with confirmed extra- or intracranial CeAD on imaging. Enrolled participants were followed for 1 year evaluating MACE as the primary endpoint. RESULTS: One-hundred ten patients were enrolled (age 53 ± 15.9, 56% Caucasian, and 50% male, BMI 28.9 ± 9.2). Grade I, II, III, and IV blunt vascular injury was noted in 16%, 33%, 19%, and 32%, respectively. Predisposing factors were noted in the majority (78%), including sneezing, carrying heavy load, chiropractic manipulation. Stent was placed in 10 (10%) subjects (extracranial carotid n = 9; intracranial carotid n = 1; extracranial vertebral n = 1) at the physician's discretion along with medical management. Reasons for stent placement were early development of high-grade stenosis or expanding pseudoaneurysm. Stented patients experienced no procedural or in-hospital complications and no MACE between discharge and 1 year follow up. CeAD patients treated with medical management only had 14% MACE at 1 year. CONCLUSION: In this single high-volume center cohort of CeAD patients, stenting was found to be beneficial, particularly with development of high-grade stenosis or expanding pseudoaneurysm. These results warrant confirmation by a randomized clinical trial.

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.

Patient-reported outcome measures for patients with cerebral aneurysms acquired via social media: data from a large nationwide sample.

BACKGROUND: With greater survival rates, patient-reported outcome measures (PROMs) among survivors of ruptured cerebral aneurysm should be an increasing concern among neurointerventionalists. Prior studies were limited in scale and generalizability. Our study aims were to (1) evaluate the validity of cerebral aneurysm PROMs obtained from social media; (2) determine the persistence of PROMs over time; and (3) determine what PROMs still exist in those with no physical impairments. METHODS: By engaging national brain aneurysm support groups and using an online questionnaire modeled after the generic EQ-5D instrument, we asked respondents to classify their health in five dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a 3-point Likert scale. RESULTS: In 2 months we received 604 responses from 46 states in the USA. Our cohort of ruptured aneurysm respondents reported PROMs similar to previously published series. Over time, headache and anxiety improved while depression, level of exercise, and return to work remained unchanged. We found that memory worsened after 2 years. Among those without any physical impairment, rates of 20.6%, 14.9%, 12.6%, and 23% were seen for significant headaches, significant memory loss, significant depression, and sense of life being negatively affected, respectively. CONCLUSIONS: Despite this novel study design, we obtained results comparable to prior studies. These results suggest that many patients with ruptured cerebral aneurysms, regardless of whether they are >2 years after the event and/or free of physical impairment, struggle with a poor quality of life. The latency, scale, and low cost of this study design may accelerate future cerebral aneurysm PROM research.

Acute global ischemic stroke after cranioplasty: case report and review of the literature.

INTRODUCTION: Cranioplasty procedures are performed usually after devastating neurological injuries requiring craniectomies. Although relatively safe, global intracerebral infarction is a poorly understood, and most often, lethal complication after cranioplasty. We report here one such case with a thorough literature review with insight as to possible etiologies of this injury. CASE REPORT: A 14-year-old girl underwent a left-sided decompressive hemicraniectomy for treatment of a subdural hematoma and cerebral edema. The patient's neurological condition eventually improved and she presented for cranioplasty repair of the defect 83 days after her initial operation. Six hours after an uneventful procedure, the patient's neurological examination declined. Immediate CT scan revealed global edema. Despite all treatment measures, the patient progressed to global ischemia and brain death and expired. CONCLUSIONS: Although global intracerebral infarction after cranioplasty is extremely rare, the concepts of vessel injury, venous stasis, and reperfusion into dysfunctional cerebral tissue after cranioplasty should be considered when evaluating the risk of this procedure.

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.

Chiari I malformation associated with atlanto-occipital assimilation presenting as orthopnea and cough syncope: a case report and review of literature.

Although it is not uncommon for patients with Chiari I malformations to present with respiratory complaints, cough syncope is a rare presenting symptom. We report an adult patient who harbored both a Chiari I malformation and atlanto-occipital assimilation who complained of cough syncope, orthopnea, and central sleep apnea. The patient underwent decompressive craniectomy of the posterior fossa and cervical level 2 laminectomy. However, due to a possible initial underappreciation of the profound narrowing of the foramen magnum as a result of these concomitant pathologies, the patient may have had continued impaired cerebrospinal fluid flow, leading to a symptomatic pseudomeningocele and requiring a more extensive decompression that included a cervical level 3 laminectomy as well as a temporary lumbar drain. On 2-year follow-up, he has remained asymptomatic.

Iatrogenic traumatic intracranial aneurysm after endoscopic sinus surgery.

Iatrogenic traumatic intracranial aneurysms are rare, but their clinical impact is significant secondary to their risk of intracranial hemorrhage and in their frequent complexity in management. We report an adult patient with a history of chronic sinusitis who, while undergoing elective endoscopic polypectomy, suffered an iatrogenic injury to an A2 segment branch of the left anterior cerebral artery, resulting in a pseudoaneurysm. Management included endovascular coiling and a bicoronal craniotomy approach, using a split-thickness cranial graft and abdominal fat graft to repair the associated left cribriform plate defect.

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).

Chiari I malformation associated with atlanto-occipital assimilation presenting as orthopnea and cough syncope.

Although it is not uncommon for patients with Chiari I malformations to present with respiratory complaints, cough syncope is a rare presenting symptom. We report an adult patient who had both a Chiari I malformation and atlanto-occipital assimilation, and complained of cough syncope, orthopnea, and central sleep apnea. The patient underwent decompressive craniectomy of the posterior fossa and a cervical level 2 laminectomy. However, due to an initial under-appreciation of the profound narrowing of the foramen magnum as a result of these concomitant pathologies, the patient had continued impaired cerebrospinal fluid flow, leading to a symptomatic pseudomeningocele and required a more extensive decompression that included a cervical level 3 laminectomy as well as a temporary lumbar drain. On 2 year follow-up, he remained asymptomatic.

Initial Experience with Neuroform EZ in the Treatment of Wide-neck Cerebral Aneurysms.

PURPOSE: Stent-assisted coiling allows embolization and parent vessel reconstruction of wide-necked intracranial aneurysms. The Neuroform EZ (Boston Scientific, Fremont, CA, U.S.A.) stent delivery system offers deployment of a Neuroform stent with fewer steps and improved operator control. Initial experience, technical considerations, and treatment outcomes using the Neuroform EZ stent delivery system in combination with coil embolization are reported. MATERIALS AND METHODS: Seventeen consecutive patients harboring 21 wide-necked saccular cerebral aneurysms were treated with stent reconstruction. Twenty aneurysms were unruptured; one was treated within 24 hours of diagnosis of rupture. Twenty aneurysms were located in the anterior circulation; one was in the posterior circulation. Immediate and six-month post-treatment angiography and clinical assessment were performed. RESULTS: In all cases, the stents were delivered and positioned without difficulty in deployment. Technical complications occurred in 4 patients, but none were directly related to the stent delivery system. On immediate post-treatment angiography, 5 of 21 aneurysms showed complete occlusion, 5 of 21 showed residual neck, and 11 of 21 showed residual contrast filling of the aneurysm sac. At six month follow-up, all 17 patients were clinically stable. Angiography of 18 of the aneurysms showed total occlusion in 12, residual neck in 3, and residual aneurysm filling in 3. Retreatment was performed in the three with residual aneurysm. CONCLUSION: The Neuroform EZ stent system offers improved anchoring and support in stent delivery, which is particularly useful when multiple stents are overlapped to further protect the parent vessel and increase flow diversion away from the aneurysm sac. The only significant problem encountered was coil prolapse, which could be treated with a second stent when necessary. The ease of deployment improves upon the already clinically successful Neuroform design.

Frontal sinus schwannoma: case report and review of literature.

Although schwannomas are frequently found in the head and neck region, sinonasal tract involvement is extremely rare, especially those of the frontal sinus. We report a patient with an incidentally found right frontal sinus lesion. The patient underwent resection of the tumor via a right craniotomy. The histological diagnosis was consistent with a schwannoma. There has been no radiographic recurrence on 2-year follow-up.

Major intratumoral hemorrhage of a petroclival atypical meningioma: case report and review of literature.

Spontaneous intratumoral hemorrhage associated with a meningioma is an extremely rare event and has a very high rate of morbidity and mortality. We report a patient with a history of subtotal resection of a petroclival meningioma followed by gamma knife radiosurgery who presented with sudden neurological deterioration following intratumoral hemorrhage after 4 asymptomatic years. The patient underwent early resection of this atypical meningioma and evacuation of hematoma via a retrosigmoid transpetrosal approach and had rapid neurological improvement.

Hydrocephalus in posterior fossa lesions: ventriculostomy and permanent shunt rates by diagnosis.

OBJECTIVES: The rate of ventriculostomy for acute hydrocephalus and progression to shunt-dependent chronic hydrocephalus in patients with posterior fossa lesions are not well known. METHODS: We retrospectively reviewed 104 consecutive cases with posterior fossa lesions on admission to the University of Illinois Hospital from June 2002 to December 2005. We recorded the rate of ventriculostomy and permanent ventricular shunting, which were compared among etiologic groups, using chi-squared and Fisher's exact tests. RESULTS: Overall, 35 patients had ventriculostomy for acute hydrocephalus and 16 had permanent shunting for shunt-dependent chronic hydrocephalus. Of those with primary posterior fossa intracranial hemorrhage (ICH) (42 cases), 19 (45%) required ventriculostomy, with five (26%) requiring subsequent permanent shunting; 13 patients had hematoma evacuation, with two having permanent shunting. Of those with cerebellar infarction (14 cases), four (29%) required ventriculostomy and one (25%) had a permanent shunt; two had a decompressive craniectomy. Of those with neoplasms (43 cases, 33 surgically resected), ten (23%) required ventriculostomy and nine (21%) required permanent shunting. In addition, two of the three cases with infectious processes required ventriculostomy and one required a permanent shunt. In-hospital mortality was 21% (9/42 cases) for patients with ICH, 14% (2/14 cases) for patients with infarction and 0% for all others. DISCUSSION: Acute primary posterior fossa hemorrhage has the highest rate of ventriculostomy for acute hydrocephalus and highest inpatient mortality but a surprisingly low rate of permanent shunt-dependency. When hydrocephalus was caused by a neoplasm, there was a higher rate of permanent shunt placement.

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.

Survival and early differentiation of human neural stem cells transplanted in a nonhuman primate model of stroke.

OBJECT: Neural cell transplantation has been proposed as a treatment after stroke. The purpose of this study was to establish if human neural stem cells (HNSCs) could survive in the nonhuman primate brain after an ischemic event. METHODS: Three adult cynomolgus monkeys received a unilateral occlusion of the M, segment of the right middle cerebral artery (MCA). One week later each animal received five magnetic resonance (MR) image-guided stereotactic intracerebral injections of HNSC neurospheres labeled with bromodeoxyuridine (BrdU) in the areas surrounding the ischemic lesion as defined in T1- and T2-weighted images. On the day of transplantation and throughout the study the monkeys received oral cyclosporine (10 mg/kg twice a day), and plasma levels were monitored routinely. The animals were killed at 45, 75, or 105 days after transplantation. Magnetic resonance images revealed a cortical and subcortical infarction in the MCA distribution area. Postmortem morphological brain analyses confirmed the distribution of the infarcted area seen in the MR images, with loss of tissue and necrosis in the ischemic region. Cells that were positive for BrdU were present in the three experimental monkeys, mainly along injection tracks. Double-label immunofluorescence for BrdU and betaIII-tubulin (a marker of young neurons) revealed colocalization of few HNSCs, most of which were observed outside the immediate injection site. Colocalization with nestin was also observed, indicating an early neural/glial fate. CONCLUSIONS: In a model of stroke in nonhuman primates, HNSCs can survive up to 105 days when transplanted 1 week after an ischemic event and can partly undergo neuronal differentiation.

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.