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.

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.

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.

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.

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.

Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain.

Stem cell transplantation promises new hope for the treatment of stroke although significant questions remain about how the grafted cells elicit their effects. One hypothesis is that transplanted stem cells enhance endogenous repair mechanisms activated after cerebral ischaemia. Recognizing that bilateral reorganization of surviving circuits is associated with recovery after stroke, we investigated the ability of transplanted human neural progenitor cells to enhance this structural plasticity. Our results show the first evidence that human neural progenitor cell treatment can significantly increase dendritic plasticity in both the ipsi- and contralesional cortex and this coincides with stem cell-induced functional recovery. Moreover, stem cell-grafted rats demonstrated increased corticocortical, corticostriatal, corticothalamic and corticospinal axonal rewiring from the contralesional side; with the transcallosal and corticospinal axonal sprouting correlating with functional recovery. Furthermore, we demonstrate that axonal transport, which is critical for both proper axonal function and axonal sprouting, is inhibited by stroke and that this is rescued by the stem cell treatment, thus identifying another novel potential mechanism of action of transplanted cells. Finally, we established in vitro co-culture assays in which these stem cells mimicked the effects observed in vivo. Through immunodepletion studies, we identified vascular endothelial growth factor, thrombospondins 1 and 2, and slit as mediators partially responsible for stem cell-induced effects on dendritic sprouting, axonal plasticity and axonal transport in vitro. Thus, we postulate that human neural progenitor cells aid recovery after stroke through secretion of factors that enhance brain repair and plasticity.

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.

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.

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.

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.

Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists.

Despite the fact that consensus guidelines recommend long-term dopamine agonist (DA) therapy as a first-line approach to the treatment of small prolactinoma, some patients continue to prefer a primary surgical approach. Concerns over potential adverse effects of long-term medical therapy and/or the desire to become pregnant and avoid long-term medication are often mentioned as reasons to pursue surgical removal. In this retrospective study, 34 consecutive patients (30 female, 4 male) preferably underwent primary pituitary surgery without prior DA treatment for small prolactinomas (microprolactinoma 1-10 mm, macroprolactinoma 11-20 mm) at the Department of Neurosurgery, University of Bern, Switzerland. At the time of diagnosis, 31 of 34 patients (91%) presented with symptoms. Patients with microprolactinomas had significantly lower preoperative prolactin (PRL) levels compared to patients with macroprolactinomas (median 143 µg/l vs. 340 µg/l). Ninety percent of symptomatic patients experienced significant improvement of their signs and symptoms upon surgery. The postoperative PRL levels (median 3.45 µg/l) returned to normal in 94% of patients with small prolactinomas. There was no mortality and no major morbidities. One patient suffered from hypogonadotropic hypogonadism after surgery despite postoperative normal PRL levels. Long-term remission was achieved in 22 of 24 patients (91%) with microprolactinomas, and in 8 of 10 patients (80%) with macroprolactinomas after a median follow-up period of 33.5 months. Patients with small prolactinomas can safely consider pituitary surgery in a specialized centre with good chance of long-term remission as an alternative to long-term DA therapy.

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.

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.

Biodistribution of neural stem cells after intravascular therapy for hypoxic-ischemia.

BACKGROUND AND PURPOSE: Intravascular transplantation of neural stem cells represents a minimally invasive therapeutic approach for the treatment of central nervous system diseases. The cellular biodistribution after intravascular injection needs to be analyzed to determine the ideal delivery modality. We studied the biodistribution and efficiency of targeted central nervous system delivery comparing intravenous and intra-arterial (IA) administration of neural stem cells after brain ischemia. METHODS: Mouse neural stem cells were transduced with a firefly luciferase reporter gene for bioluminescence imaging (BLI). Hypoxic-ischemia was induced in adult mice and reporter neural stem cells were transplanted IA or intravenous at 24 hours after brain ischemia. In vivo BLI was used to track transplanted cells up to 2 weeks after transplantation and ex vivo BLI was used to determine single organ biodistribution. RESULTS: Immediately after transplantation, BLI signal from the brain was 12 times higher in IA versus intravenous injected animals (P<0.0001). After IA injection, 69% of the total luciferase activity arose from the brain early after transplantation and 93% at 1 week. After intravenous injection, 94% of the BLI signal was detected in the lungs (P=0.004) followed by an overall 94% signal loss at 1 week, indicating lack of cell survival outside the brain. Ex vivo single organ analysis showed a significantly higher BLI signal in the brain than in the lungs, liver, and kidneys at 1 week (P<0.0001) and 2 weeks in IA (P=0.007). CONCLUSIONS: IA transplantation results in superior delivery and sustained presence of neural stem cells in the ischemic brain in comparison to intravenous infusion.

Optimizing the success of cell transplantation therapy for stroke.

Stem cell transplantation has evolved as a promising experimental treatment approach for stroke. In this review, we address the major hurdles for successful translation from basic research into clinical applications and discuss possible strategies to overcome these issues. We summarize the results from present pre-clinical and clinical studies and focus on specific areas of current controversy and research: (i) the therapeutic time window for cell transplantation; (ii) the selection of patients likely to benefit from such a therapy; (iii) the optimal route of cell delivery to the ischemic brain; (iv) the most suitable cell types and sources; (v) the potential mechanisms of functional recovery after cell transplantation; and (vi) the development of imaging techniques to monitor cell therapy.

Intraoperative hypothermia during vascular neurosurgical procedures.

Increasing evidence in animal models and clinical trials for stroke, hypoxic encephalopathy for children, and traumatic brain injury have shown that mild hypothermia may attenuate ischemic damage and improve neurological outcome. However, it is less clear if mild intraoperative hypothermia during vascular neurosurgical procedures results in improved outcomes for patients. This review examines the scientific evidence behind hypothermia as a treatment and discusses factors that may be important for the use of this adjuvant technique, including cooling temperature, duration of hypothermia, and rate of rewarming.

Restorative neuroscience: concepts and perspectives.

There is increasing interest in the search for therapeutic options for diseases and injuries of the central nervous system (CNS), for which currently no effective treatment strategies are available. Replacement of damaged cells and restoration of function can be accomplished by transplantation of cells derived from different sources, such as human foetal tissue, genetically modified cell lines, embryonic or somatic stem cells. Preclinical and clinical trials have shown promising results in neurodegenerative disorders, like Parkinson's and Huntington's disease, but also ischaemic stroke, intracerebral haemorrhage, demyelinating disorders, epilepsy and traumatic lesions of the brain and spinal cord. Other studies have focused on finding new ways to activate and direct endogenous repair mechanisms in the CNS, eg, by exposure to specific neuronal growth factors or by inactivating inhibitory molecules. Neuroprotective drugs may offer an additional tool for improving neuronal survival in acute or chronic CNS diseases. Importantly however, a number of scientific issues need to be addressed in order to permit the introduction of these experimental techniques in the wider clinical setting.

Intravascular cell replacement therapy for stroke.

The use of stem cell transplantation to restore neurological function after stroke is being recognized as a potential novel therapy. Before stem cell transplantation can become widely applicable, however, questions remain about the optimal site of delivery and timing of transplantation. In particular, there seems to be increasing evidence that intravascular cell delivery after stroke is a viable alternative to intracerebral transplantation. In this review, the authors focus on the intravascular delivery of stem cells for stroke treatment with an emphasis on timing, transendothelial migration and possible mechanisms leading to neuroprotection, angiogenesis, immunomodulation, and neural plasticity. They also review current concepts of in vivo imaging and tracking of stem cells after stroke.

Cell replacement therapy for intracerebral hemorrhage.

Intracerebral hemorrhage (ICH), for which no effective treatment strategy is currently available, constitutes one of the most devastating forms of stroke. As a result, developing therapeutic options for ICH is of great interest to the medical community. The 3 potential therapies that have the most promise are cell replacement therapy, enhancing endogenous repair mechanisms, and utilizing various neuroprotective drugs. Replacement of damaged cells and restoration of function can be accomplished by transplantation of cells derived from different sources, such as embryonic or somatic stem cells, umbilical cord blood, and genetically modified cell lines. Early experimental data showing the benefits of cell transplantation on functional recovery after ICH have been promising. Nevertheless, several studies have focused on another therapeutic avenue, investigating novel ways to activate and direct endogenous repair mechanisms in the central nervous system, through exposure to specific neuronal growth factors or by inactivating inhibitory molecules. Lastly, neuroprotective drugs may offer an additional tool for improving neuronal survival in the perihematomal area. However, a number of scientific issues must be addressed before these experimental techniques can be translated into clinical therapy. In this review, the authors outline the recent advances in the basic science of treatment strategies for ICH.

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.