Carotid-vertebral artery bypass with saphenous vein graft for symptomatic vertebrobasilar insufficiency.

OBJECTIVESymptomatic steno-occlusion of the proximal vertebral artery (VA) or subclavian artery (ScA) heralds a poor prognosis and high risk of stroke recurrence despite medical therapy, including antiplatelet or anticoagulant drugs. In some cases, the V2 segment of the cervical VA is patent and perfused via collateral vessels. The authors describe 7 patients who were successfully treated by external carotid artery (ECA)-saphenous vein (SV)-VA bypass.METHODSSeven cases involving symptomatic patients were retrospectively studied: 3 cases of V1 segment occlusion, 2 cases of severe in-stent restenosis in the V1 segment, and 2 cases of occlusion of the proximal ScA. All patients underwent ECA-SV-VA bypass. The ECA was isolated and retracted, and the anterior wall of the transverse foramen was unroofed. The VA was exposed, and then the 2 ends of the SV were anastomosed to the VA and ECA in an end-to-side fashion.RESULTSSurgical procedures were all performed as planned, with no intraoperative complications. There were 2 postoperative complications (severe laryngeal edema in one case and shoulder weakness in another), but both patients recovered fully and measures were taken to minimize laryngeal edema and its effects in subsequent cases. All patients experienced improvement of their symptoms. No new neurological deficits were reported. Postoperative angiography demonstrated that the anastomoses were all patent, and analysis of follow-up data (range of follow-up 12-78 months) revealed no further ischemic events in the vertebrobasilar territory.CONCLUSIONSThe ECA-SV-VA bypass is a useful treatment for patients who suffer medically refractory ischemic events in the vertebrobasilar territory when the proximal part of the VA or ScA is severely stenosed or occluded but the V2 segment of the cervical VA is patent.

Transcranial Doppler ultrasonography in neurological surgery and neurocritical care.

Transcranial Doppler (TCD) ultrasonography is an inexpensive, noninvasive means of measuring blood flow within the arteries of the brain. In this review, the authors outline the technology underlying TCD ultrasonography and describe its uses in patients with neurosurgical diseases. One of the most common uses of TCD ultrasonography is monitoring for vasospasm following subarachnoid hemorrhage. In this setting, elevated blood flow velocities serve as a proxy for vasospasm and can herald the onset of ischemia. TCD ultrasonography is also useful in the evaluation and management of occlusive cerebrovascular disease. Monitoring for microembolic signals enables stratification of stroke risk due to carotid stenosis and can also be used to clarify stroke etiology. TCD ultrasonography can identify patients with exhausted cerebrovascular reserve, and after extracranial-intracranial bypass procedures it can be used to assess adequacy of flow through the graft. Finally, assessment of cerebral autoregulation can be performed using TCD ultrasonography, providing data important to the management of patients with severe traumatic brain injury. As the clinical applications of TCD ultrasonography have expanded over time, so has their importance in the management of neurosurgical patients. Familiarity with this diagnostic tool is crucial for the modern neurological surgeon.

A step-down unit transfer protocol for low-risk aneurysmal subarachnoid hemorrhage.

OBJECTIVE Patients who have experienced subarachnoid hemorrhage (SAH) often receive care in the setting of the ICU. However, SAH patients may not all require extended ICU admission. The authors established a protocol on January 1, 2015, to transfer select, low-risk patients to a step-down unit (SDU) to streamline care for SAH patients. This study describes the results of the implemented protocol. METHODS In this retrospective chart review, patients presenting with SAH between January 2011 and September 2016 were reviewed for inclusion. The control group consisted of patients admitted prior to establishment of the SDU transfer protocol, while the intervention group consisted of patients admitted afterward. RESULTS Of the patients in the intervention group, 79.2% (57/72) were transferred to the SDU during their admission. Of these transferred patients, 29.8% (17/57) required return to the neurosurgical ICU (NSICU). There were no instances of morbidity or mortality directly related to care in the SDU. Patients in the intervention group had a mean reduced NSICU length of stay, by 1.95 days, which trended toward significance, and a longer average hospitalization, by 2.7 days, which also trended toward significance. In-hospital mortality and 90-day readmission rate were not statistically different between the groups. In addition, early transfer timing prior to 7 days was associated with neither a higher return rate to the NSICU nor higher 90-day readmission rate. CONCLUSIONS In this retrospective study, the authors demonstrated that the transfer protocol was safe, feasible, and effective in reducing the ICU length of stay and was independent of transfer timing. Confirmation of these results is needed in a large, multicenter study.

Traumatic brain injury and intracranial hemorrhage-induced cerebral vasospasm: a systematic review.

OBJECTIVE Little is known regarding the natural history of posttraumatic vasospasm. The authors review the pathophysiology of posttraumatic vasospasm (PTV), its associated risk factors, the efficacy of the technologies used to detect PTV, and the management/treatment options available today. METHODS The authors performed a systematic review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the following databases: PubMed, Google Scholar, and CENTRAL (the Cochrane Central Register of Controlled Trials). Outcome variables extracted from each study included epidemiology, pathophysiology, time course, predictors of PTV and delayed cerebral ischemia (DCI), optimal means of surveillance and evaluation of PTV, application of multimodality monitoring, modern management and treatment options, and patient outcomes after PTV. Study types were limited to retrospective chart reviews, database reviews, and prospective studies. RESULTS A total of 40 articles were included in the systematic review. In many cases of mild or moderate traumatic brain injury (TBI), imaging or ultrasonographic studies are not performed. The lack of widespread assessment makes finding the true overall incidence of PTV a difficult endeavor. The clinical consequences of PTV are important, given the morbidity that can result from it. DCI manifests as new-onset neurological deterioration that occurs beyond the timeframe of initial brain injury. While there are many techniques that attempt to diagnose cerebral vasospasm, digital subtraction angiography is the gold standard. Some predictors of PTV include SAH, intraventricular hemorrhage, low admission Glasgow Coma Scale (GCS) score (< 9), and young age (< 30 years). CONCLUSIONS Given these results, clinicians should suspect PTV in young patients presenting with intracranial hemorrhage (ICH), especially SAH and/or intraventricular hemorrhage, who present with a GCS score less than 9. Monitoring and regulation of CNS metabolism following TBI/ICH-induced vasospasm may play an important adjunct role to the primary prevention of vasospasm.

Advanced imaging in acute ischemic stroke.

The evaluation and management of acute ischemic stroke has primarily relied on the use of conventional CT and MRI techniques as well as lumen imaging sequences such as CT angiography (CTA) and MR angiography (MRA). Several newer or less-established imaging modalities, including vessel wall MRI, transcranial Doppler ultrasonography, and 4D CTA and MRA, are being developed to complement conventional CT and MRI techniques. Vessel wall MRI provides high-resolution analysis of both extracranial and intracranial vasculature to help identify previously occult lesions or characteristics of lesions that may portend a worse natural history. Transcranial Doppler ultrasonography can be used in the acute setting as a minimally invasive way of identifying large vessel occlusions or monitoring the response to stroke treatment. It can also be used to assist in the workup for cryptogenic stroke or to diagnose a patent foramen ovale. Four-dimensional CTA and MRA provide a less invasive alternative to digital subtraction angiography to determine the extent of the clot burden and the degree of collateral blood flow in large vessel occlusions. Along with technological advances, these new imaging modalities are improving the diagnosis, workup, and management of acute ischemic stroke- roles that will continue to expand in the future.

Lessons for the pathogenesis of vasospasm from a patient with sickle cell disease, moyamoya disease, subarachnoid hemorrhage, and 1 month of persistent vasospasm: illustrative case.

BACKGROUND: The mechanism of vasospasm post-subarachnoid hemorrhage (post-SAH) is a poorly understood yet devastating complication that can result in delayed ischemic neurological damage. High concentrations of free hemoglobin present in hemolytic conditions reduce nitric oxide (NO) availability which may disrupt vascular dynamics and contribute to the extent of vasospasm. OBSERVATIONS: The authors describe the clinical course of a sickle cell disease (SCD) patient with spontaneous SAH who suffered an abnormally long duration of vasospasm. The authors then present a focused review of the pathology of intravascular hemolysis and discuss the potential key role of intravascular hemolysis in the pathogenesis of cerebral vasospasm as illustrated in this case lesson. LESSONS: Abnormally prolonged and severe vasospasm in SCD with SAH may provide clues regarding the mechanisms of vasospasm. Intravascular hemolysis limits NO availability and may contribute to the development of vasospasm following SAH.

A critical comparison between the semisitting and the supine positioning in vestibular schwannoma surgery: subgroup analysis of a randomized, multicenter trial.

OBJECTIVE: Patient positioning in vestibular schwannoma (VS) surgery is a matter of ongoing discussion. Factors to consider include preservation of cranial nerve functions, extent of tumor resection, and complications. The objective of this study was to determine the optimal patient positioning in VS surgery. METHODS: A subgroup analysis of a randomized, multicenter trial that investigated the efficacy of prophylactic nimodipine in VS surgery was performed to investigate the impact of positioning (semisitting or supine) on extent of resection, functional outcomes, and complications. The data of 97 patients were collected prospectively. All procedures were performed via a retrosigmoid approach. The semisitting position was chosen in 56 patients, whereas 41 patients were treated while supine. RESULTS: Complete resection was obtained at a higher percentage in the semisitting as compared to the supine position (93% vs 73%, p = 0.002). Logistic regression analysis revealed significantly better facial nerve function in the early postoperative course in the semisitting group (p = 0.004), particularly concerning severe facial nerve paresis (House-Brackmann grade IV or worse; p = 0.002). One year after surgery, facial nerve function recovered. However, there was still a tendency for better facial nerve function in the semisitting group (p = 0.091). There were no significant differences between groups regarding hearing preservation rates. Venous air embolism with the necessity to terminate surgery occurred in 2 patients in the semisitting position (3.6%). Supplementary analysis with a 2-tailed permutation randomization with 10,000 permutations of treatment choice and a propensity score matching showed either a tendency or significant results for better facial nerve outcomes in the early postoperative course and extent of resection in the semisitting group. CONCLUSIONS: Although the results of the various statistical analyses are not uniform, the data indicate better results concerning both a higher rate of complete removal (according to the intraoperative impression of the surgeon) and facial nerve function after a semisitting as compared to the supine position. These advantages may justify the potential higher risk for severe complications of the semisitting position in VS surgery. The choice of positioning has to consider all individual patient parameters and risks carefully.

Perioperative near-infrared spectroscopy cerebral oxygen saturation in symptomatic pediatric hydrocephalus patients at risk for intracranial hypertension.

OBJECTIVE: The lack of a continuous, noninvasive modality for monitoring intracranial pressure (ICP) is a major obstacle in the care of pediatric patients with hydrocephalus who are at risk for intracranial hypertension. Intracranial hypertension can lead to cerebral ischemia and brain tissue hypoxia. In this study, the authors evaluated the use of near-infrared spectroscopy (NIRS) to measure regional cerebral oxygen saturation (rSO2) in symptomatic pediatric patients with hydrocephalus concerning for elevated ICP. METHODS: The authors evaluated the NIRS rSO2 trends in pediatric patients presenting with acute hydrocephalus and clinical symptoms of intracranial hypertension. NIRS rSO2 values were recorded hourly before and after neurosurgical intervention. To test for significance between preoperative and postoperative values, the authors constructed a linear regression model with the rSO2 values as the outcome and pre- and postsurgery cohorts as the independent variable, adjusted for age and sex, and used the generalized estimating equation method to account for within-subject correlation. RESULTS: Twenty-two pediatric patients underwent NIRS rSO2 monitoring before and after CSF diversion surgery. The mean durations of NIRS rSO2 recording pre- and postoperatively were 13.95 and 26.82 hours, respectively. The mean pre- and postoperative rSO2 values were 73.84% and 80.65%, respectively, and the adjusted mean difference estimated from the regression model was 5.98% (adjusted p < 0.0001), suggestive of improved cerebral oxygenation after definitive neurosurgical CSF diversion treatment. Postoperatively, all patients returned to baseline neurological status with no clinical symptoms of elevated ICP. CONCLUSIONS: Cerebral oxygenation trends measured by NIRS in symptomatic pediatric hydrocephalus patients with intracranial hypertension generally improve after CSF diversion surgery.

Evidence for a conditioning effect of inhalational anesthetics on angiographic vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is characterized by large-artery vasospasm, distal autoregulatory dysfunction, cortical spreading depression, and microvessel thrombi. Large-artery vasospasm has been identified as an independent predictor of poor outcome in numerous studies. Recently, several animal studies have identified a strong protective role for inhalational anesthetics against secondary brain injury after SAH including DCI-a phenomenon referred to as anesthetic conditioning. The aim of the present study was to assess the potential role of inhalational anesthetics against cerebral vasospasm and DCI in patients suffering from an SAH. METHODS: After IRB approval, data were collected retrospectively for all SAH patients admitted to the authors' hospital between January 1, 2010, and December 31, 2013, who received general anesthesia with either inhalational anesthetics only (sevoflurane or desflurane) or combined inhalational (sevoflurane or desflurane) and intravenous (propofol) anesthetics during aneurysm treatment. The primary outcomes were development of angiographic vasospasm and development of DCI during hospitalization. Univariate and logistic regression analyses were performed to identify independent predictors of these endpoints. RESULTS: The cohort included 157 SAH patients whose mean age was 56 ± 14 (± SD). An inhalational anesthetic-only technique was employed in 119 patients (76%), while a combination of inhalational and intravenous anesthetics was employed in 34 patients (22%). As expected, patients in the inhalational anesthetic-only group were exposed to significantly more inhalational agent than patients in the combination anesthetic group (p < 0.05). Multivariate logistic regression analysis identified inhalational anesthetic-only technique (OR 0.35, 95% CI 0.14-0.89), Hunt and Hess grade (OR 1.51, 95% CI 1.03-2.22), and diabetes (OR 0.19, 95% CI 0.06-0.55) as significant predictors of angiographic vasospasm. In contradistinction, the inhalational anesthetic-only technique had no significant impact on the incidence of DCI or functional outcome at discharge, though greater exposure to desflurane (as measured by end-tidal concentration) was associated with a lower incidence of DCI. CONCLUSIONS: These data represent the first evidence in humans that inhalational anesthetics may exert a conditioning protective effect against angiographic vasospasm in SAH patients. Future studies will be needed to determine whether optimized inhalational anesthetic paradigms produce definitive protection against angiographic vasospasm; whether they protect against other events leading to secondary brain injury after SAH, including microvascular thrombi, autoregulatory dysfunction, blood-brain barrier breakdown, neuroinflammation, and neuronal cell death; and, if so, whether this protection ultimately improves patient outcome.

When the air hits your brain: decreased arterial pulsatility after craniectomy leading to impaired glymphatic flow.

OBJECTIVECranial neurosurgical procedures can cause changes in brain function. There are many potential explanations, but the effect of simply opening the skull has not been addressed, except for research into syndrome of the trephined. The glymphatic circulation, by which CSF and interstitial fluid circulate through periarterial spaces, brain parenchyma, and perivenous spaces, depends on arterial pulsations to provide the driving force for bulk flow; opening the cranial cavity could dampen this force. The authors hypothesized that a craniectomy, without any other pathological insult, is sufficient to alter brain function due to reduced arterial pulsatility and decreased glymphatic flow. Furthermore, they postulated that glymphatic impairment would produce activation of astrocytes and microglia; with the reestablishment of a closed cranial compartment, the glymphatic impairment, astrocytic/microglial activation, and neurobehavioral decline caused by opening the cranial compartment might be reversed.METHODSUsing two-photon in vivo microscopy, the pulsatility index of cortical vessels was quantified through a thinned murine skull and then again after craniectomy. Glymphatic influx was determined with ex vivo fluorescence microscopy of mice 0, 14, 28, and 56 days following craniectomy or cranioplasty; brain sections were immunohistochemically labeled for GFAP and CD68. Motor and cognitive performance was quantified with rotarod and novel object recognition tests at baseline and 14, 21, and 28 days following craniectomy or cranioplasty.RESULTSPenetrating arterial pulsatility decreased significantly and bilaterally following unilateral craniectomy, producing immediate and chronic impairment of glymphatic CSF influx in the ipsilateral and contralateral brain parenchyma. Craniectomy-related glymphatic dysfunction was associated with an astrocytic and microglial inflammatory response, as well as with the development of motor and cognitive deficits. Recovery of glymphatic flow preceded reduced gliosis and return of normal neurological function, and cranioplasty accelerated this recovery.CONCLUSIONSCraniectomy causes glymphatic dysfunction, gliosis, and changes in neurological function in this murine model of syndrome of the trephined.

Decrease of blood flow velocity in the middle cerebral artery after stellate ganglion block following aneurysmal subarachnoid hemorrhage: a potential vasospasm treatment?

OBJECTIVE: Cerebral vasospasm (CV) is a delayed, sustained contraction of the cerebral arteries that tends to occur 3-14 days after aneurysmal subarachnoid hemorrhage (aSAH) from a ruptured aneurysm. Vasospasm potentially leads to delayed cerebral ischemia, and despite medical treatment, 1 of 3 patients suffer a persistent neurological deficit. Bedside transcranial Doppler (TCD) ultrasonography is used to indirectly detect CV through recognition of an increase in cerebral blood flow velocity (CBFV). The present study aimed to use TCD ultrasonography to monitor how CBFV changes on both the ipsi- and contralateral sides of the brain in the first 24 hours after patients have received a stellate ganglion block (SGB) to treat CV that persists despite maximum standard therapy. METHODS: The data were culled from records of patients treated between 2013 and 2017. Patients were included if an SGB was administered following aSAH, whose CBFV was ≥ 120 cm/sec and who had either a focal neurological deficit or reduced consciousness despite having received medical treatment and blood pressure management. The SGB was performed on the side where the highest CBFV had been recorded with 8-10 ml ropivacaine 0.2%. The patient's CBFV was reassessed after 2 and 24 hours. RESULTS: Thirty-seven patients (male/female ratio 18:19), age 17-70 years (mean age 49.9 ± 11.1), who harbored 13 clipped and 22 coiled aneurysms (1 patient received both a coil and a clip, and 3 patients had 3 untreated aneurysms) had at least one SGB. Patients received up to 4 SGBs, and thus the study comprised a total of 76 SGBs.After the first SGB, CBFV decreased in 80.5% of patients after 2 hours, from a mean of 160.3 ± 28.2 cm/sec to 127.5 ± 34.3 cm/sec (p < 0.001), and it further decreased in 63.4% after 24 hours to 137.2 ± 38.2 cm/sec (p = 0.007). A similar significant effect was found for the subsequent SGB. Adding clonidine showed no significant effect on either the onset or the duration of the SGB. Contralateral middle cerebral artery (MCA) blood flow was not reduced by the SGB. CONCLUSIONS: To the authors' knowledge, this is the largest study on the effects of administering an SGB to aSAH patients after aneurysm rupture. The data showed a significant reduction in ipsilateral CBFV (MCA 20.5%) after SGB, lasting in about two-thirds of cases for over 24 hours with no major complications resulting from the SGB.

Intracranial pressure before and after cranioplasty: insights into intracranial physiology.

OBJECTIVE: Decompressive craniectomy (DC) is an emergency neurosurgical procedure used in cases of severe intracranial hypertension or impending intracranial herniation. The procedure is often lifesaving, but it exposes the brain to atmospheric pressure in the subsequent rehabilitation period, which changes intracranial physiology and probably leads to complications such as hydrocephalus, hygromas, and "syndrome of the trephined." The objective of the study was to study the effect of cranioplasty on intracranial pressure (ICP), postural ICP changes, and intracranial pulse wave amplitude (PWA). METHODS: The authors performed a prospective observational study including patients who underwent DC during a 12-month period. Telemetric ICP sensors were implanted in all patients at the time of DC. ICP was evaluated before and after cranioplasty during weekly measurement sessions including a standardized postural change program. RESULTS: Twelve of the 17 patients enrolled in the study had cranioplasty performed and were included in the present investigation. Their mean ICP in the supine position increased from -0.5 ± 4.8 mm Hg the week before cranioplasty to 6.3 ± 2.5 mm Hg the week after cranioplasty (p < 0.0001), whereas the mean ICP in the sitting position was unchanged (-1.2 ± 4.8 vs -1.1 ± 3.6 mm Hg, p = 0.90). The difference in ICP between the supine and sitting positions was minimal before cranioplasty (1.1 ± 1.8 mm Hg) and increased to 7.4 ± 3.6 mm Hg in the week following cranioplasty (p < 0.0001). During the succeeding 2 weeks of the follow-up period, the mean ICP in the supine and sitting positions decreased in parallel to, respectively, 4.6 ± 3.0 mm Hg (p = 0.0003) and -3.9 ± 2.7 mm Hg (p = 0.040), meaning that the postural ICP difference remained constant at around 8 mm Hg. The mean intracranial PWA increased from 0.7 ± 0.7 mm Hg to 2.9 ± 0.8 mm Hg after cranioplasty (p < 0.0001) and remained around 3 mm Hg throughout the following weeks. CONCLUSIONS: Cranioplasty restores normal intracranial physiology regarding postural ICP changes and intracranial PWA. These findings complement those of previous investigations on cerebral blood flow and cerebral metabolism in patients after decompressive craniectomy.

Computed tomography angiography accuracy in brain death diagnosis.

OBJECTIVE: The present study was designed to answer several concerns disclosed by systematic reviews indicating no evidence to support the use of computed tomography angiography (CTA) in the diagnosis of brain death (BD). Therefore, the aim of this study was to assess the effectiveness of CTA for the diagnosis of BD and to define the optimal tomographic criteria of intracranial circulatory arrest. METHODS: A unicenter, prospective, observational case-control study was undertaken. Comatose patients (Glasgow Coma Scale score ≤ 5), even those presenting with the first signs of BD, were included. CTA scanning of arterial and venous vasculature and transcranial Doppler (TCD) were performed. A neurological determination of BD and consequently determination of case (BD group) or control (no-BD group) was conducted. All personnel involved with assessing patients were blinded to further tests results. Accuracy of BD diagnosis determined by using CTA was calculated based on the criteria of bilateral absence of visualization of the internal cerebral veins and the distal middle cerebral arteries, the 4-point score (4PS), and an exclusive criterion of absence of deep brain venous drainage as indicated by the absence of deep venous opacification on CTA, the venous score (VS), which considers only the internal cerebral veins bilaterally. RESULTS: A total of 106 patients were enrolled in this study; 52 patients did not have BD, and none of these patients had circulatory arrest observed by CTA or TCD (100% specificity). Of the 54 patients with a clinical diagnosis of BD, 33 met the 4PS (61.1% sensitivity), whereas 47 met the VS (87% sensitivity). The accuracy of CTA was time related, with greater accuracy when scanning was performed less than 12 hours prior to the neurological assessment, reaching 95.5% sensitivity with the VS. CONCLUSIONS: CTA can reliably support a diagnosis of BD. The criterion of the absence of deep venous opacification, which can be assessed by use of the VS criteria investigated in this study, can confirm the occurrence of cerebral circulatory arrest.Clinical trial registration no.: 12500913400000068 (clinicaltrials.gov).

Secondary hemorrhagic complications in aneurysmal subarachnoid hemorrhage: when the impact hits hard.

OBJECTIVE: Clinical data on secondary hemorrhagic complications (SHCs) in patients with aneurysmal subarachnoid hemorrhage (SAH) are sparse and mostly limited to ventriculostomy-associated SHCs. This study aimed to elucidate the incidence, risk factors, and impact on outcome of SHCs in a large cohort of SAH patients. METHODS: All consecutive patients with ruptured aneurysms treated between January 2003 and June 2016 were eligible for this study. Patients' charts were reviewed for clinical data, and imaging studies were reviewed for radiographic data. SHCs were divided into those associated with ventriculostomy and those not associated with ventriculostomy, as well as into major and minor bleeding forms, depending on clinical impact. RESULTS: Sixty-two (6.6%) of the 939 patients included in the final analysis developed SHCs. Ventriculostomy-associated bleedings (n = 16) were independently predicted by mono- or dual-antiplatelet therapy after aneurysm treatment (p = 0.028, adjusted odds ratio [aOR] = 10.28; and p = 0.026, aOR = 14.25, respectively) but showed no impact on functional outcome after SAH. Periinterventional use of thrombolytic agents for early effective anticoagulation was the only independent predictor (p = 0.010, aOR = 4.27) of major SHCs (n = 38, 61.3%) in endovascularly treated patients. In turn, a major SHC was independently associated with poor outcome at the 6-month follow-up (modified Rankin Scale score > 3). Blood thinning drug therapy prior to SAH was not associated with SHC risk. CONCLUSIONS: SHCs present a rare sequela of SAH. Antiplatelet therapy during (but not before) SAH increases the risk of ventriculostomy-associated bleedings, but without further impact on the course and outcome of SAH. The use of thrombolytic agents for early effective anticoagulation carries relevant risk for major SHCs and poor outcome.

Detection of delayed cerebral ischemia using objective pupillometry in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm causing delayed cerebral ischemia (DCI) is a source of significant morbidity after subarachnoid hemorrhage (SAH). Transcranial Doppler is used at most institutions to detect sonographic vasospasm but has poor positive predictive value for DCI. Automated assessment of the pupillary light reflex has been increasingly used as a reliable way of assessing pupillary reactivity, and the Neurological Pupil Index (NPi) has been shown to decrease hours prior to the clinical manifestation of ischemic injury or herniation syndromes. The aim of this study was to investigate the role of automated pupillometry in the setting of SAH, as a potential adjunct to TCD. METHODS: Our analysis included patients that had been diagnosed with aneurysmal SAH and admitted to the neuro-intensive care unit of the University of Texas Southwestern Medical Center between November 2015 and June 2017. A dynamic infrared pupillometer was used for all pupillary measurements. An NPi value ranging from 3 to 5 was considered normal, and from 0 to 2.9 abnormal. Sonographic vasospasm was defined as middle cerebral artery velocities greater than 100 cm/sec with a Lindegaard ratio greater than 3 on either side on transcranial Doppler. Most patients had multiple NPi readings daily and we retained the lowest value for our analysis. We aimed to study the association between DCI and sonographic vasospasm, and DCI and NPi readings. RESULTS: A total of 56 patients were included in the final analysis with 635 paired observations of daily TCD and NPi data. There was no statistically significant association between the NPi value and the presence of sonographic vasospasm. There was a significant association between DCI and sonographic vasospasm, χ2(1) = 6.4112, p = 0.0113, OR 1.6419 (95% CI 1.1163-2.4150), and between DCI and an abnormal decrease in NPi, χ2(1) = 38.4456, p < 0.001, OR 3.3930 (95% CI 2.2789-5.0517). Twelve patients experienced DCI, with 7 showing a decrease of their NPi to an abnormal range. This change occurred > 8 hours prior to the clinical decline 71.4% of the time. The NPi normalized in all patients after treatment of their vasospasm. CONCLUSIONS: Isolated sonographic vasospasm does not seem to correlate with NPi changes, as the latter likely reflects an ischemic neurological injury. NPi changes are strongly associated with the advent of DCI and could be an early herald of clinical deterioration.

Fully automated, real-time, calibration-free, continuous noninvasive estimation of intracranial pressure in children.

OBJECTIVE: In the search for a reliable, cooperation-independent, noninvasive alternative to invasive intracranial pressure (ICP) monitoring in children, various approaches have been proposed, but at the present time none are capable of providing fully automated, real-time, calibration-free, continuous and accurate ICP estimates. The authors investigated the feasibility and validity of simultaneously monitored arterial blood pressure (ABP) and middle cerebral artery (MCA) cerebral blood flow velocity (CBFV) waveforms to derive noninvasive ICP (nICP) estimates. METHODS: Invasive ICP and ABP recordings were collected from 12 pediatric and young adult patients (aged 2-25 years) undergoing such monitoring as part of routine clinical care. Additionally, simultaneous transcranial Doppler (TCD) ultrasonography-based MCA CBFV waveform measurements were performed at the bedside in dedicated data collection sessions. The ABP and MCA CBFV waveforms were analyzed in the context of a mathematical model, linking them to the cerebral vasculature's biophysical properties and ICP. The authors developed and automated a waveform preprocessing, signal-quality evaluation, and waveform-synchronization "pipeline" in order to test and objectively validate the algorithm's performance. To generate one nICP estimate, 60 beats of ABP and MCA CBFV waveform data were analyzed. Moving the 60-beat data window forward by one beat at a time (overlapping data windows) resulted in 39,480 ICP-to-nICP comparisons across a total of 44 data-collection sessions (studies). Moving the 60-beat data window forward by 60 beats at a time (nonoverlapping data windows) resulted in 722 paired ICP-to-nICP comparisons. RESULTS: Greater than 80% of all nICP estimates fell within ± 7 mm Hg of the reference measurement. Overall performance in the nonoverlapping data window approach gave a mean error (bias) of 1.0 mm Hg, standard deviation of the error (precision) of 5.1 mm Hg, and root-mean-square error of 5.2 mm Hg. The associated mean and median absolute errors were 4.2 mm Hg and 3.3 mm Hg, respectively. These results were contingent on ensuring adequate ABP and CBFV signal quality and required accurate hydrostatic pressure correction of the measured ABP waveform in relation to the elevation of the external auditory meatus. Notably, the procedure had no failed attempts at data collection, and all patients had adequate TCD data from at least one hemisphere. Last, an analysis of using study-by-study averaged nICP estimates to detect a measured ICP > 15 mm Hg resulted in an area under the receiver operating characteristic curve of 0.83, with a sensitivity of 71% and specificity of 86% for a detection threshold of nICP = 15 mm Hg. CONCLUSIONS: This nICP estimation algorithm, based on ABP and bedside TCD CBFV waveform measurements, performs in a manner comparable to invasive ICP monitoring. These findings open the possibility for rational, point-of-care treatment decisions in pediatric patients with suspected raised ICP undergoing intensive care.

Whole blood levels of S1PR4 mRNA associated with cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: The authors sought to identify mRNA biomarkers of cerebral vasospasm in whole blood of patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A prospective transcriptomic study for vasospasm was conducted in whole blood samples of 44 aSAH patients who developed (VSP+ group, n = 22) or did not develop (VSP- group, n = 22) vasospasm. Samples from all patients were profiled for 21,460 mRNA probes using the Illumina Human HT12v4.0 array. Differential statistical analysis was performed using a linear mixed model. RESULTS: Levels of sphingosine-1-phosphate receptor 4 (S1PR4) mRNA were significantly higher (p = 8.03 × 10-6) at presentation in patients who developed vasospasm after aSAH than in patients who did not. CONCLUSIONS: The results, which are consistent with findings of previous experimental investigations conducted in animal models, support the role of S1PR4 and its ligand, sphingosine-1-phosphate (S1P), in arterial-associated vasoconstriction, which suggests that S1PR4 could be used as a biomarker for cerebral vasospasm in aSAH patients.

Paradoxical cerebrovascular hemodynamic changes with nicardipine.

OBJECTIVE Intravenous nicardipine is commonly used for blood pressure reduction in patients with acute stroke. However, few studies have described its effects on cerebrovascular hemodynamics as measured by transcranial Doppler (TCD) waveform analysis and pulsatility index (PI). In this study, the authors report examples of a consistent but paradoxical finding associated with nicardipine that suggests intracranial vasoconstriction, contrary to what is expected from a vasodilator. METHODS The data presented are from a convenience sample of patients who underwent TCD monitoring before, after, or during nicardipine administration. In each case, TCD waveform morphologies and PIs were compared. RESULTS The TCD waveforms during nicardipine infusion are characterized by a prominent systolic peak and dicrotic notch. Systolic deceleration was more pronounced and PIs were significantly elevated in patients who were on nicardipine (p < 0.001). This finding was not evident when patients were not on nicardipine. CONCLUSIONS This study provides the first evidence of paradoxical intracranial vasoconstriction associated with intravenous nicardipine. In the authors' experience, this finding is consistently encountered in the vast majority of patients who are treated with intravenous nicardipine, and is contradictory to what is expected from a vasodilator. Future studies are needed to confirm this finding in larger populations and diverse clinical settings and to examine mechanisms that explain this phenomenon.

Carotid atherosclerotic plaque instability and cognition determined by ultrasound-measured plaque strain in asymptomatic patients with significant stenosis.

OBJECTIVE This article describes the use of ultrasound measurements of physical strain within carotid atherosclerotic plaques as a measure of instability and the potential for vascular cognitive decline, microemboli, and white matter changes. METHODS Asymptomatic patients with significant (> 60%) carotid artery stenosis were studied for dynamic measures of plaque instability, presence of microemboli, white matter changes, and vascular cognitive decline in comparison with normative controls and premorbid state. RESULTS Although classically asymptomatic, these patients showed vascular cognitive decline. The degree of strain instability measured within the atherosclerotic plaque directly predicted vascular cognitive decline in these patients thought previously to be asymptomatic according to classic criteria. Furthermore, 26% of patients showed microemboli, and patients had twice as much white matter hyperintensity as controls. CONCLUSIONS These data show that physical measures of plaque instability are possible through interpretation of ultrasound strain data during pulsation, which may be more clinically relevant than solely measuring degree of stenosis. The data also highlight the importance of understanding that the definition of symptoms should not be limited to motor, speech, and vision function but underscore the role of vascular cognitive decline in the pathophysiology of carotid atherosclerotic disease. Clinical trial registration no.: NCT02476396 (clinicaltrials.gov).

The impact of temporary clipping during aneurysm surgery on the incidence of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE Clipping of a ruptured intracranial aneurysm requires some degree of vessel manipulation, which in turn is believed to contribute to vasoconstriction. One of the techniques used during surgery is temporary clipping of the parent vessel. Temporary clipping may either be mandatory in cases of premature rupture (rescue) or represent a precautionary or facilitating surgical step (elective). The aim of this study was to study the association between temporary clipping during aneurysm surgery and the incidence of vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH) in a large clinical series. METHODS Seven hundred seventy-eight patients who underwent surgical aneurysm treatment after aSAH were retrospectively included in the study. In addition to surgical parameters, the authors recorded transcranial Doppler (TCD) sonography-documented vasospasm (TCD-vasospasm, blood flow acceleration > 120 cm/sec), delayed ischemic neurological deficits (DINDs), and delayed cerebral infarction (DCI). Multivariate binary logistic regression analysis was applied to assess the association between temporary clipping, vasospasm, DIND, and DCI. RESULTS Temporary clipping was performed in 338 (43.4%) of 778 patients during aneurysm surgery. TCD sonographic flow acceleration developed in 370 (47.6%), DINDs in 123 (15.8%), and DCI in 97 (12.5%). Patients with temporary clipping showed no significant increase in the incidence of TCD-vasospasm compared with patients without temporary clipping (49% vs 48%, respectively; p = 0.60). DINDs developed in 12% of patients with temporary clipping and 18% of those without temporary clipping (p = 0.01). DCI occurred in 9% of patients with temporary clipping and 15% of those without temporary clipping (p = 0.02). The need for rescue temporary clipping was a predictor for DCI; 19.5% of patients in the rescue temporary clipping group but only 11.3% in the elective temporary clipping group had infarcts (p = 0.02). Elective temporary clipping was not associated with TCD-vasospasm (p = 0.31), DIND (p = 0.18), or DCI (p = 0.06). CONCLUSIONS Temporary clipping did not contribute to a higher rate of TCD-vasospasm, DIND, or DCI in comparison with rates in patients without temporary clipping. In contrast, there was an association between temporary clipping and a lower incidence of DINDs and DCI. There is no reason to be hesitant in using elective temporary clipping if deemed appropriate.