Prediction of Long-Term Restenosis After Carotid Endarterectomy Using Quantitative Magnetic Resonance Angiography.

Background: To detect restenosis after carotid endarterectomy (CEA), long-term monitoring is required. However, non-selective follow-up is controversial and can be limited by costs and logistical considerations. Objective: To examine the value of immediate perioperative vessel flow measurements after CEA using quantitative magnetic resonance angiography (QMRA) to detect patients at risk of long-term restenosis. Methods: A prospective cohort study with long-term sonographic follow-up after CEA for symptomatic internal carotid artery stenosis (ICAs) > 50%. In all patients, vessel flow has been assessed both pre- and postoperatively using QMRA within ±3 days of surgery. Data on QMRA assessment were analyzed to identify patients at risk of restenosis for up to 10 years. Results: Restenosis was recorded in 4 of 24 patients (17%) at a median follow-up of 6.8 ± 2.6 years. None of them experienced an ischemic event. Perioperative flow differences were significantly greater in patients without long-term restenosis, both for the ipsilateral ICA (p < 0.001) and MCA (p = 0.03), compared to those with restenosis (p = 0.22 and p = 0.3, respectively). The ICA mean flow ratio (p = 0.05) tended to be more effective than the MCA ratio in predicting restenosis over the long term (p = 0.35). Conclusion: Our preliminary findings suggest that QMRA-based mean flow increases after CEA may be predictive of restenosis over the long term. Perioperative QMRA assessment could become an operator-independent screening tool to identify a subgroup of patients at risk for restenosis, in whom long-term monitoring is advised.

Impact of primary medical or surgical therapy on prolactinoma patients' BMI and metabolic profile over the long-term.

OBJECTIVES: High prolactin levels have been associated with weight gain and impaired metabolic profiles. While treatment with dopamine agonists (DAs) has been shown to improve these parameters, there is a lack of surgical series on its comparative effect in prolactinoma patients. METHODS: In this retrospective, comparative study, consecutive patients with a prolactinoma were enrolled if treated with first-line transsphenoidal surgery (TSS) or with DAs. Patients with prolactinomas of Knosp grade >2 and those with a follow-up <24 months were excluded, as were patients with missing laboratory metabolic parameters at baseline and over the long-term. Effects of either treatment on BMI and the metabolic profile were analyzed, and independent risk factors for long-term obesity were calculated. RESULTS: Primary treatment was TSS for 12 patients (40%) and DAs for 18 patients (60%). At diagnosis, no significant differences between the two cohorts were observed with regard to adenoma size, Knosp grading, baseline prolactin (PRL) levels, prevalence of hypogonadism, or laboratory metabolic parameters. Mean follow-up was 51.9 months (range, 24-158). Over the long-term, both TSS and DAs led to the control of hyperprolactinemia (92% vs. 72%) and hypogonadism (78% vs. 83%) in the majority of patients. While a significant decrease in patients' BMI and fasting glucose were observed, changes in the lipid profile were marginal and independent of the treatment modality. At baseline, increased BMI-but not the primary treatment strategy-was an independent predictor of long-term obesity. CONCLUSIONS: Over the long-term, patients' BMI and FG improve, but changes in the metabolic profile are marginal and independent of the primary treatment. It is presumable that not DAs per se, but rather the control of hyperprolactinemia plays a role in patients' metabolic profile alterations.

Lateral one-third gland resection in Cushing patients with failed adenoma identification leads to low remission rates: long-term observations from a small, single-center cohort.

BACKGROUND: Currently, there are no guidelines for neurosurgeons treating patients with Cushing's disease (CD) when intraoperative adenoma identification is negative. Under these circumstances, a total hypophysectomy or hemi-hypophysectomy on the side indicated by inferior petrosal sinus sampling (IPSS) is the approach being used, although there is a subsequent risk of hypopituitarism. Data on whether one-third lateral pituitary gland resection results in cure of hypercortisolism and low rates of hypopituitarism remain inconclusive. METHODS: Retrospective single-center study of CD patients with failed intraoperative adenoma identification and subsequent resection of the lateral one-third of the pituitary gland as predicted by IPSS. We assessed (i) histopathological findings, (ii) early and long-term remission rates, and (iii) rates of additional pituitary hormone insufficiency. RESULTS: Ten women and three men met the inclusion criteria. At 3 months, remission was noted in six (46%) patients: three (23%) had histologically confirmed adenomas, two (15%) had ACTH hyperplasia, and one patient (8%) was positive for Crooke's hyaline degeneration. New pituitary hormone deficits were noted in two patients (15%). After a median (±SD) follow-up of 14±4 years, recurrence was noted in two (15%) patients. Long-term control of hypercortisolism was attained by 10 patients (77%), with additional therapies required in nine (69%) of them. CONCLUSIONS: In CD patients with failed intraoperative adenoma visualization, lateral one-third gland resection resulted in low morbidity and long-term remission in 31% of patients without the need for additional therapies. Bearing in mind the sample size of this audit, the indication for lateral one-third-gland resection has to be critically appraised and discussed with the patients before surgery.

Persistent bone impairment despite long-term control of hyperprolactinemia and hypogonadism in men and women with prolactinomas.

While prolactinoma patients have high bone turnover, current data are inconclusive when it comes to determining whether correction of hyperprolactinemia and associated hypogandism improves osteodensitometric data in men and women over the long term. In a large cohort of including 40 men and 60 women, we studied the long-term impact of prolactinoma treatment on bone mineral density (BMD) in men versus women, assessed adverse effects of a primary surgical or medical approach, and evaluated data for risk factors for impaired BMD at last follow-up using multivariate regression analyses. Median duration of follow-up was 79 months (range 13-408 months). Our data indicate that the prevalence of impaired BMD remained significantly higher in men (37%) than in women (7%, p < 0.001), despite the fact that hyperprolactinemia and hypogonadism are under control in the majority of men. We found that persistent hyperprolactinemia and male sex were independent risk factors for long-term bone impairment. Currently, osteoporosis prevention and treatment focus primarily on women, yet special attention to bone loss in men with prolactinomas is advised. Bone impairment as "end organ" reflects the full range of the disease and could become a surrogate marker for the severity of long-lasting hyperprolactinemia and associated hypogonadism.

Influence of inferior petrosal sinus drainage symmetry on detection of adenomas in Cushing's syndrome.

BACKGROUND: Asymmetric inferior petrosal sinuses (IPS) are not infrequently encountered during bilateral IPS sampling. There is little data on whether IPS symmetry influences success in predicting the adenoma side in patients with ACTH-dependent Cushing's syndrome (CS). OBJECTIVE: To assess the influence of IPS drainage patterns on detection of an adenoma in CS. METHODS: Retrospective single-center cohort analysis reviewing records of patients with CS and negative MRI findings who subsequently underwent BIPSS. RESULTS: BIPSS was performed in 38 patients with a mean age of 45±15 years. The overall technical success rate was 97% for bilateral cannulation. Asymmetric IPS were observed in 11 (39%) patients with Cushing's disease (CD). A side-to-side ACTH ratio was not significantly different between patients with symmetric outflow and those with asymmetric outflow at baseline (8.6±2.7 versus 16.4±6.0; P=0.45), but ratios were significantly different after ovine corticotropin-releasing hormone (oCRH) stimulation (6.0±2.5 versus 35.7±22.5; P=0.03). BIPSS correctly predicted the side of the adenoma in 25 (96%) patients with CD. Prediction was better when the venous outflow was symmetric (100%) rather than asymmetric (93%), although the difference was not significant (P=0.42). Remission from CS was achieved in 32 patients (87%), independent of the symmetry of IPS. CONCLUSIONS: Bearing in mind the sample size of this audit, asymmetric IPS at least do not seem to diminish the accuracy of diagnosis of ACTH-dependent CS, nor do they influence the clinical outcome.

Quantitative magnetic resonance angiography as a potential predictor for cerebral hyperperfusion syndrome: a preliminary study.

OBJECTIVE Cerebral hyperperfusion syndrome (CHS) is a rare but devastating complication of carotid endarterectomy (CEA). This study sought to determine whether quantitative hemodynamic assessment using MR angiography can stratify CHS risk. METHODS In this prospective trial, patients with internal carotid artery (ICA) stenosis were randomly selected for pre- and postoperative quantitative phase-contrast MR angiography (QMRA). Assessment was standardized according to a protocol and included Doppler/duplex sonography, MRI, and/or CT angiography and QMRA of the intra- and extracranial supplying arteries of the brain. Clinical and radiological data were analyzed to identify CHS risk factors. RESULTS Twenty-five of 153 patients who underwent CEA for ICA stenosis were randomly selected for pre- and postoperative QMRA. QMRA data showed a 2.2-fold postoperative increase in blood flow in the operated ICA (p < 0.001) and a 1.3-fold increase in the ipsilateral middle cerebral artery (MCA) (p = 0.01). Four patients had clinically manifested CHS. The mean flow increases in the patients with CHS were significantly higher than in the patients without CHS, both in the ICA and MCA (p < 0.001). Female sex and a low preoperative diastolic blood pressure were the clearest clinical risk factors for CHS, whereas the flow differences and absolute postoperative flow values in the ipsilateral ICA and MCA were identified as potential radiological predictors for CHS. CONCLUSIONS Cerebral blood flow in the ipsilateral ICA and MCA as assessed by QMRA significantly increased after CEA. Higher mean flow differences in ICA and MCA were associated with the development of CHS. QMRA might have the potential to become a noninvasive, operator-independent screening tool for identifying patients at risk for CHS.

Intracranial Foreign Body in a Patient With Paranoid Schizophrenia.

Self-inflicted penetrating head injuries in patients with paranoid schizophrenia are an infrequent phenomenon. The authors report on a psychiatric patient who presented with epistaxis. Computed tomography showed a nail passing from the nasal cavity into the frontal lobe. Given the proximity to large intracranial vessels, a craniotomy was performed and the nail was retracted. The patient later reported having hammered the nail into the nasal cavity with the intention to "kill the voice in my head." Despite use of the latest imaging modalities, metal artifacts may have limited the assessment of vascular involvement. Surgical decision-making preventing secondary damage is crucial in them.

"Sentinel Seizure" as a Warning Sign Preceding Fatal Rupture of a Giant Middle Cerebral Artery Aneurysm.

BACKGROUND: Sentinel headache is a well-known warning sign preceding subarachnoid hemorrhage (SAH) caused by rupture of an intracranial aneurysm. New-onset seizure or "sentinel seizure" preceding aneurysmal SAH, however, is uncommon. CASE DESCRIPTION: We report a 51-year-old man with a new-onset seizure. Diagnostic workup revealed a giant middle cerebral artery aneurysm without evidence of subarachnoid or intracerebral hemorrhage. Antiepileptic therapy was initiated, elective diagnostic angiography and subsequent treatment was scheduled, and the patient was discharged home. Four days later, he suddenly lost consciousness and subsequently died of a massive aneurysmal SAH. CONCLUSIONS: As with sentinel headache, new-onset seizures in patients with unruptured intracranial aneurysms might prompt immediate treatment to prevent imminent SAH with its subsequent high morbidity and mortality.

10-year follow-up study comparing primary medical vs. surgical therapy in women with prolactinomas.

While dopamine-agonists are the first-line approach in treating prolactinomas, surgery can be considered in selected cases besides non-responders or patients with dopamine-agonist intolerance. The aim of the present study was to compare the long-term outcome in women with prolactinomas treated primarily either surgically or medically who had not had prior dopamine-agonist treatment. Retrospective case-note study of all consecutive women with prolactinomas primarily managed with medical therapy or surgery in a tertiary referral centre. The clinical, biochemical, and radiological responses to first-line treatment at early and long-term follow-up were analysed. The primary therapeutic strategy was dopamine-agonists for 36 (34 %) and surgery for 71 (66 %) of the women. Baseline clinical and biochemical characteristics were not significantly different between the primary surgical and medical cohort. Median follow-up time was 90 months (range 13-408). Following primary treatment, prolactin level significantly decreased in both cohorts, on average to 13.5 µg/L (IQR 7-21; p < 0.001), and was within the normal range in 82 % of all patients. No women in the surgical cohort demonstrated permanent sequelae and morbidity was low. At final follow-up, control of hyperprolactinaemia required dopamine-agonist therapy in 64 % of women who had undergone primary medical therapy vs. 32 % of those who had primary surgical therapy (p = 0.003). Logistic regression revealed that the primary therapeutic strategy, but not adenoma size, was an independent risk factor for long-term dependence on dopamine-agonists. The present data indicate that in a dedicated tertiary referral centre, long-term control of hyperprolactinaemia in women with prolactinomas is high. In selected cases, a primary neurosurgical approach might at least be interdisciplinarily discussed with the primary goal of minimizing long-term dependence on dopamine-agonists.

Long-Term Follow-Up of Primary Medical Versus Surgical Treatment of Prolactinomas in Men: Effects on Hyperprolactinemia, Hypogonadism, and Bone Health.

OBJECTIVE: In men with prolactinomas, impaired bone density is the principle consequence of hyperprolactinemia-induced hypogonadism. Although dopamine agonists (DAs) are the first-line approach in prolactinomas, surgery can be considered in selected cases. In this study, we aimed to investigate the long-term control of hyperprolactinemia, hypogonadism, and bone health comparing primary medical and surgical therapy in men who had not had prior DA treatment. METHODS: This is a retrospective case-note study of 44 consecutive men with prolactinomas and no prior DAs managed in a single tertiary referral center. Clinical, biochemical, and radiologic response to the first-line approach were analyzed in the 2 cohorts. RESULTS: Mean age at diagnosis was 47 years (range, 22-78 years). The prevalence of hypogonadism was 86%, and 27% of patients had pathologic bone density at baseline. The primary therapeutic strategy was surgery for 34% and DAs for 66% of patients. Median long-term follow-up was 63 months (range, 17-238 months). Long-term control of hyperprolactinemia required DAs in 53% of patients with primary surgical therapy, versus 90% of patients with primary medical therapy (P = 0.02). Hypogonadism was controlled in 73% of patients. The prevalence of patients with pathologic bone density was 37% at last follow-up, with no differences between the 2 therapeutic cohorts (P = 0.48). CONCLUSIONS: Despite control of hyperprolactinemia and hypogonadism in most patients independent of the primary treatment modality, the prevalence of impaired bone health status remains high, and osteodensitometry should be recommended.

Stereolithographic models in the interdisciplinary planning of treatment for complex intracranial aneurysms.

BACKGROUND: Treatment of complex intracranial aneurysms requires strategic pre-interventional or preoperative planning. In addition to modern three-dimensional (3D) rotational angiography, computed tomography angiography (CTA) or magnetic resonance angiogram (MRA), a solid, tangible 3D model may improve anatomical comprehension and treatment planning. A 3D rapid prototyping (RP) technique based on multimodal imaging data was evaluated for use in planning of treatment for complex aneurysmal configurations. METHODS: Six patients with complex aneurysms were selected for 3D RP based on CTA and 3D rotational angiography data. Images were segmented using image-processing software to create virtual 3D models. Three-dimensional rapid prototyping techniques transformed the imaging data into physical 3D models, which were used and evaluated for interdisciplinary treatment planning. RESULTS: In all cases, the model provided a comprehensive 3D representation of relevant anatomical structures and improved understanding of related vessels. Based on the 3D model, primary bypass surgery with subsequent reconstruction of the aneurysm was then considered advantageous in all but one patient after simulation of multiple approaches. CONCLUSIONS: Preoperative prediction of intraoperative anatomy using the 3D model was considered helpful for treatment planning. The use of 3D rapid prototyping may enhance understanding of complex configurations in selected large or giant aneurysms, especially those pretreated with clips or coils.

The effects of creatine supplementation on striatal neural progenitor cells depend on developmental stage.

Transplantation of neural progenitor cells (NPCs) is a promising experimental therapy for Huntington's disease (HD). The variables responsible for the success of this approach, including selection of the optimal developmental stage of the grafted cells, are however largely unknown. Supporting cellular energy metabolism by creatine (Cr) supplementation is a clinically translatable method for improving cell transplantation strategies. The present study aims at investigating differences between early (E14) and late (E18) developmental stages of rat striatal NPCs in vitro. NPCs were isolated from E14 and E18 embryos and cultured for 7 days with or without Cr [5 mM]. Chronic treatment significantly increased the percentage of GABA-immunoreactive neurons as compared to untreated controls, both in the E14 (170.4 ± 4.7 %) and the E18 groups (129.3 ± 9.3 %). This effect was greater in E14 cultures (p < 0.05). Similarly, short-term treatment for 24 h resulted in increased induction (p < 0.05) of the GABA-ergic phenotype in E14 (163.0 ± 10.4 %), compared to E18 cultures (133.3 ± 9.5 %). Total neuronal cell numbers and general viability were not affected by Cr (p > 0.05). Protective effects of Cr against a metabolic insult were equal in E14 and E18 NPCs (p > 0.05). Cr exposure promoted morphological differentiation of GABA-ergic neurons, including neurite length in both groups (p < 0.05), but the number of branching points was increased only in the E18 group (p < 0.05). Our results demonstrate that the role of Cr as a GABA-ergic differentiation factor depends on the developmental stage of striatal NPCs, while Cr-mediated neuroprotection is not significantly influenced. These findings have potential implications for optimizing future cell replacement strategies in HD.

Creatine supplementation improves neural progenitor cell survival in Huntington's disease.

Preclinical and clinical studies suggest that striatal transplantation of neural stem cells (NSCs) and neural progenitor cells (NPCs) may be an appealing and valuable system for treating Huntington's disease. Nevertheless, for a neural replacement to become an effective translational treatment for Huntington's disease, a certain number of difficulties must be addressed, including how to improve the integration of transplanted cell grafts with the host tissue, to elevate the survival rates of transplanted cells, and to ensure their directed differentiation into specific neuronal phenotypes. Research focusing on the translational applications of creatine (Cr) supplementation in NSC and NPC cell replacement therapies continues to offer promising results, pointing to Cr as a factor with the potential to improve cell graft survivability and encourage differentiation toward GABAergic phenotypes in models of striatal transplantation. Here, we evaluate research examining the outcomes of Cr supplementation and how the timing of supplementation regimes may affect their efficacy. The recent studies indicate that Cr's effects vary according to the developmental stage of the cells being treated, noting the dynamic differences in creatine kinase expression over the developmental stages of differentiating NPCs. This research continues to move Cr supplementation closer to the widespread clinical application and suggests such techniques warrant further examination.

Rapid Recurrence of a Benign Meningial Perineurioma.

BACKGROUND: We describe a rare case of a rapidly recurring benign meningial-based perineurioma. Clinical, radiologic, and pathologic features of a rapidly recurring falxial perineurioma are described; the perineurioma was discovered incidentally in an 86-year-old woman. CASE DESCRIPTION: Due to progressive gait disturbances and radiologically proven progression after a 3-year symptom-free interval, subtotal resection of a large falxial-based meningeal tumor was performed. CONCLUSIONS: The pathologic examination confirmed the diagnosis of a perineurioma (World Health Organization grade I). Follow-up magnetic resonance tomography 5 months later due to neurologic deterioration revealed an abnormally rapidly growing and extensive local tumor recurrence. Due to the mass effect, reoperation was performed and adjuvant radiation of 20 Gy to the tumor bed was implemented thereafter. Meningeal-based perineuriomas of the central nervous system are extremely rare, and literature on proper management is scarce. Although histologic classification reveals a benign lesion, follow-up may be considered for this type of tumor.

Two-stage carotid saphenous vein interposition graft and superficial temporal artery bypass for acute carotid occlusion.

The safety and efficacy of bypass surgery to achieve cerebral revascularization for cerebral hypoperfusion are controversial. However, bypass surgery still plays an important role for a select group of patients. The indication to perform a high-flow or low-flow bypass in cases of acute symptomatic artery occlusion is not defined. Neurologic symptoms in acute symptomatic occlusion are usually blood pressure dependent, and acute blood flow restoration may be considered. This report reviews the case of a patient with an acute carotid occlusion in which a two-stage bypass technique was used to achieve revascularization and discusses the issues influencing the decision-making.

Monitoring cerebral oxygenation during balloon occlusion with multichannel NIRS.

We report on oxygenation changes noninvasively recorded by multichannel continuous-wave near infrared spectroscopy (CW-NIRS) during endovascular neuroradiologic interventions requiring temporary balloon occlusion of arteries supplying the cerebral circulation. Digital subtraction angiography (DSA) provides reference data on the site, timing, and effectiveness of the flow stagnation as well as on the amount and direction of collateral circulation. This setting allows us to relate CW-NIRS findings to brain specific perfusion changes. We focused our analysis on the transition from normal perfusion to vessel occlusion, i.e., before hypoxia becomes clinically apparent. The localization of the maximal response correlated either with the core (occlusion of the middle cerebral artery) or with the watershed areas (occlusion of the internal carotid artery) of the respective vascular territories. In one patient with clinically and angiographically confirmed insufficient collateral flow during carotid artery occlusion, the total hemoglobin concentration became significantly asymmetric, with decreased values in the ipsilateral watershed area and contralaterally increased values. Multichannel CW-NIRS monitoring might serve as an objective and early predictive marker of critical perfusion changes during interventions-to prevent hypoxic damage of the brain. It also might provide valuable human reference data on oxygenation changes as they typically occur during acute stroke.

Neural progenitor cells regulate microglia functions and activity.

We found mouse neural progenitor cells (NPCs) to have a secretory protein profile distinct from other brain cells and to modulate microglial activation, proliferation and phagocytosis. NPC-derived vascular endothelial growth factor was necessary and sufficient to exert at least some of these effects in mice. Thus, neural precursor cells may not only be shaped by microglia, but also regulate microglia functions and activity.

Restenosis after microsurgical non-patch carotid endarterectomy in 586 patients.

BACKGROUND: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic (>50%) and asymptomatic (>60%) carotid artery stenosis. Here we report the midterm results of a microsurgical non-patch technique and compare these findings to those in the literature. METHODS: From 1998 to 2009 we treated 586 consecutive patients with CEA. CEA was performed, under general anesthesia, with a surgical microscope using a non-patch technique. Somatosensory evoked potential and transcranial Doppler were continuously monitored. Cross-clamping was performed under EEG burst suppression and adaptive blood pressure increase. Follow-up was performed by an independent neurologist. Mortality at 30 days and morbidity such as major and minor stroke, peripheral nerve palsy, hematoma and cardiac complications were recorded. The restenosis rate was assessed using duplex sonography 1 year after surgery. RESULTS: A total of 439 (75%) patients had symptomatic and 147 (25%) asymptomatic stenosis; 49.7% of the stenoses were on the right-side. Major perioperative strokes occurred in five (0.9%) patients [n = 4 (0.9%) symptomatic; n = 1 (0.7%) asymptomatic patients]. Minor stroke was recorded in six (1%) patients [n = 4 (0.9%) symptomatic; n = 2 (1.3%) asymptomatic patients]. Two patients with symptomatic stenoses died within 1 month after surgery. Nine patients (1.5%) had reversible peripheral nerve palsies, and nine patients (1.5%) suffered a perioperative myocardial infarction. High-grade (>70%) restenosis at 1 year was observed in 19 (3.2%) patients [n = 12 (2.7%) symptomatic; n = 7 (4.7%) asymptomatic patients]. CONCLUSIONS: The midterm rate of restenosis was low when using a microscope-assisted non-patch endarterectomy technique. The 30-day morbidity and mortality rate was comparable or lower than those in recently published surgical series.

Selective inferior petrosal sinus sampling without venous outflow diversion in the detection of a pituitary adenoma in Cushing's syndrome.

INTRODUCTION: Conventional MRI may still be an inaccurate method for the non-invasive detection of a microadenoma in adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) with ovine corticotropin-releasing hormone (oCRH) stimulation is an invasive, but accurate, intervention in the diagnostic armamentarium surrounding CS. Until now, there is a continuous controversial debate regarding lateralization data in detecting a microadenoma. Using BIPSS, we evaluated whether a highly selective placement of microcatheters without diversion of venous outflow might improve detection of pituitary microadenoma. METHODS: We performed BIPSS in 23 patients that met clinical and biochemical criteria of CS and with equivocal MRI findings. For BIPSS, the femoral veins were catheterized bilaterally with a 6-F catheter and the inferior petrosal sinus bilaterally with a 2.7-F microcatheter. A third catheter was placed in the right femoral vein. Blood samples were collected from each catheter to determine ACTH blood concentration before and after oCRH stimulation. RESULTS: In 21 patients, a central-to-peripheral ACTH gradient was found and the affected side determined. In 18 of 20 patients where transsphenoidal partial hypophysectomy was performed based on BIPSS findings, microadenoma was histologically confirmed. BIPSS had a sensitivity of 94% and a specificity of 67% after oCRH stimulation in detecting a microadenoma. Correct localization of the adenoma was achieved in all Cushing's disease patients. CONCLUSION: BIPSS remains the gold standard in the detection of a microadenoma in CS. Our findings show that the selective placement of microcatheters without venous outflow diversion might further enhance better recognition to localize the pituitary tumor.

The CCR2/CCL2 interaction mediates the transendothelial recruitment of intravascularly delivered neural stem cells to the ischemic brain.

BACKGROUND AND PURPOSE: The inflammatory response is a critical component of ischemic stroke. In addition to its physiological role, the mechanisms behind transendothelial recruitment of immune cells also offer a unique therapeutic opportunity for translational stem cell therapies. Recent reports have demonstrated homing of neural stem cells (NSC) into the injured brain areas after intravascular delivery. However, the mechanisms underlying the process of transendothelial recruitment remain largely unknown. Here we describe the critical role of the chemokine CCL2 and its receptor CCR2 in targeted homing of NSC after ischemia. METHODS: Twenty-four hours after induction of stroke using the hypoxia-ischemia model in mice CCR2+/+ and CCR2-/- reporter NSC were intra-arterially delivered. Histology and bioluminescence imaging were used to investigate NSC homing to the ischemic brain. Functional outcome was assessed with the horizontal ladder test. RESULTS: Using NSC isolated from CCR2+/+ and CCR2-/- mice, we show that receptor deficiency significantly impaired transendothelial diapedesis specifically in response to CCL2. Accordingly, wild-type NSC injected into CCL2-/- mice exhibited significantly decreased homing. Bioluminescence imaging showed robust recruitment of CCR2+/+ cells within 6 hours after transplantation in contrast to CCR2-/- cells. Mice receiving CCR2+/+ grafts after ischemic injury showed a significantly improved recovery of neurological deficits as compared to animals with transplantation of CCR2-/- NSC. CONCLUSIONS: The CCL2/CCR2 interaction is critical for transendothelial recruitment of intravascularly delivered NSC in response to ischemic injury. This finding could have significant implications in advancing minimally invasive intravascular therapeutics for regenerative medicine or cell-based drug delivery systems for central nervous system diseases.