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PURPOSE: The routine use of intraoperative digital subtraction angiography (iDSA) increases detection of intracranial aneurysm (IA) remnants after microsurgical clipping. Spontaneous thrombosis of IA remnants after clipping is considered a rare phenomenon. We analyse iDSA characteristics to find predictors for IA remnant thrombosis. METHODS: IA with intraoperative detection of a remnant after clipping were identified and divided into remnants experiencing spontaneous thrombosis, and remnants with long-term patency and/or remnant growth. Angiographic features of iDSA were analysed and compared between the two groups. RESULTS: Of 37 IAs with intraoperative remnant on 3D-iDSA, five sustained a spontaneous remnant thrombosis and remained occluded in long-term follow-up. In all five cases, iDSA revealed delayed inflow and consequent stasis of the contrast agent until the late venous phase. On the other hand, in all cases with persistent long-term IA remnants (n = 32) iDSA demonstrated timely arterial contrast inflow and wash-out without stasis of intra-aneurysmal contrast agent. CONCLUSIONS: Contrast stasis in IA remnants during iDSA appears to predict long-term IA occlusion, indicating that clip correction manoeuvres or even attempted endovascular treatment of the remnant IA may be avoided in these patients.
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Angiografia Digital , Meios de Contraste , Aneurisma Intracraniano , Humanos , Angiografia Digital/métodos , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Angiografia Cerebral/métodos , Procedimentos Neurocirúrgicos/métodos , Microcirurgia/métodos , Estudos Retrospectivos , Instrumentos CirúrgicosRESUMO
PURPOSE: Erectile dysfunction (ED) is frequently underreported in men suffering from prolactinomas and can be challenging to manage. Both dopamine agonists (DAs) and transsphenoidal surgery (TSS) correct hyperprolactinemia and restore gonadal function. However, there is scarce data regarding their effectiveness in correcting ED over the long term. METHODS: This study is a retrospective single-center comparative cohort study analyzing men diagnosed with prolactinomas, both with and without confirmed erectile dysfunction (ED) at diagnosis. Independent risk factors for persistent ED over the long term were examined using multivariate logistic regression. RESULTS: Among the 39 men with lactotroph adenomas, ED was one of the presenting symptoms in 22 (56%). The mean age at diagnosis was 45 ± 12 years. Surgery was the primary treatment in 6 (27%) ED patients and 8 (47%) non-ED patients. After a mean follow-up of 74 ± 48 months, remission from hyperprolactinemia was achieved in the majority (76%) of men: 71% in the non-ED cohort and 81% in the ED group (p = 0.70), regardless of the primary treatment strategy (surgical 84% versus medical 72%, p = 0.46). Long-term remission of ED was noted in 16 (73%) patients. Interestingly, high baseline BMI levels emerged as potential risk factors for persistent ED over the long term (OR 1.4, 95%CI 1.0-1.9; p = 0.04), while neither the initial adenoma size nor the primary treatment strategy (i.e., TSS vs. DAs) reached statistical significance. CONCLUSIONS: Correcting hyperprolactinemia and its associated hypogonadism significantly improves ED in the majority of men with prolactinomas over the long term, regardless of the primary treatment strategy employed. In addition to addressing endocrine deficiencies, the early initiation of weight control programs may be considered for men with lactotroph adenomas and ED. Although our study suggests an association between BMI and the risk of persistent ED, further research is needed to establish any causal relationships.
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Disfunção Erétil , Neoplasias Hipofisárias , Prolactinoma , Humanos , Masculino , Pessoa de Meia-Idade , Prolactinoma/complicações , Prolactinoma/cirurgia , Disfunção Erétil/etiologia , Estudos Retrospectivos , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Adulto , Resultado do Tratamento , Hiperprolactinemia/etiologia , Agonistas de Dopamina/uso terapêutico , Estudos de Coortes , Fatores de RiscoRESUMO
BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.
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Hemorragia Cerebral , Craniectomia Descompressiva , Humanos , Pessoa de Meia-Idade , Masculino , Craniectomia Descompressiva/métodos , Feminino , Hemorragia Cerebral/cirurgia , Idoso , Adulto , Resultado do Tratamento , Terapia CombinadaRESUMO
Background: In clinical practice, the size of adenomas is crucial for guiding prolactinoma patients towards the most suitable initial treatment. Consequently, establishing guidelines for serum prolactin level thresholds to assess prolactinoma size is essential. However, the potential impact of gender differences in prolactin levels on estimating adenoma size (micro- vs. macroadenoma) is not yet fully comprehended. Objective: To introduce a novel statistical method for deriving gender-specific prolactin thresholds to discriminate between micro- and macroadenomas and to assess their clinical utility. Methods: We present a novel, multilevel Bayesian logistic regression approach to compute observationally constrained gender-specific prolactin thresholds in a large cohort of prolactinoma patients (N = 133) with respect to dichotomized adenoma size. The robustness of the approach is examined with an ensemble machine learning approach (a so-called super learner), where the observed differences in prolactin and adenoma size between female and male patients are preserved and the initial sample size is artificially increased tenfold. Results: The framework results in a global prolactin threshold of 239.4â µg/L (95% credible interval: 44.0-451.2â µg/L) to discriminate between micro- and macroadenomas. We find evidence of gender-specific prolactin thresholds of 211.6â µg/L (95% credible interval: 29.0-426.2â µg/L) for women and 1,046.1â µg/L (95% credible interval: 582.2-2,325.9â µg/L) for men. Global (that is, gender-independent) thresholds result in a high sensitivity (0.97) and low specificity (0.57) when evaluated among men as most prolactin values are above the global threshold. Applying male-specific thresholds results in a slightly different scenario, with a high specificity (0.99) and moderate sensitivity (0.74). The male-dependent prolactin threshold shows large uncertainty and features some dependency on the choice of priors, in particular for small sample sizes. The augmented datasets demonstrate that future, larger cohorts are likely able to reduce the uncertainty range of the prolactin thresholds. Conclusions: The proposed framework represents a significant advancement in patient-centered care for treating prolactinoma patients by introducing gender-specific thresholds. These thresholds enable tailored treatment strategies by distinguishing between micro- and macroadenomas based on gender. Specifically, in men, a negative diagnosis using a universal prolactin threshold can effectively rule out a macroadenoma, while a positive diagnosis using a male-specific prolactin threshold can indicate its presence. However, the clinical utility of a female-specific prolactin threshold in our cohort is limited. This framework can be easily adapted to various biomedical settings with two subgroups having imbalanced average biomarkers and outcomes of interest. Using machine learning techniques to expand the dataset while preserving significant observed imbalances presents a valuable method for assessing the reliability of gender-specific threshold estimates. However, external cohorts are necessary to thoroughly validate our thresholds.
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Shunt-dependent hydrocephalus (HC) is a common sequela following aneurysmal subarachnoid hemorrhage (aSAH). However, there is still poor evidence regarding the optimal timing of ventriculoperitoneal shunt (VPS) placement, particularly in the context of early aSAH-associated complications such as delayed cerebral ischemia (DCI). The purpose of this study was to compare the impact of early (< 21 days after aSAH) versus late (≥ 21 days after aSAH) VPS placement on the functional clinical outcome. We retrospectively analyzed data from 82 patients with VPS placement after aSAH enrolled in our institutional database between 2011 and 2021. We compared two groups, early VPS placement (< 21 days after aSAH) versus late VPS placement (≥ 21 days after aSAH) in terms of demographics, SAH grading, radiological parameters, externalized cerebrospinal fluid diversions, DCI, VPS variables, and functional outcome. We identified 53 patients with early and 29 patients with late VPS implantation. Baseline variables, such as the modified Rankin Scale (mRS), the World Federation of Neurological Surgeons Scale, the Glasgow Coma Scale, and Fisher grade were not significantly different between the groups. Postoperatively, the mRS (p = 0.0037), the Glasgow Outcome Scale (p = 0.0037), and the extended Glasgow Outcome Scale (p = 0.0032) showed significantly better functional results in patients with early cerebrospinal fluid diversion. The rate of DCI did not differ significantly between the groups (p = 0.53). There was no difference in the rate of VPS placement associated complications (p = 0.44) or overall mortality (p = 0.39). Early shunt implantation, within 21 days after aSAH and therefore during the timeframe of possible DCI, might not be harmful in patients developing HC after aSAH.
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Isquemia Encefálica , Hidrocefalia , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/cirurgia , Derivação Ventriculoperitoneal/efeitos adversos , Estudos Retrospectivos , Hidrocefalia/cirurgia , Hidrocefalia/complicações , Isquemia Encefálica/cirurgia , Isquemia Encefálica/complicações , Infarto Cerebral/complicaçõesRESUMO
Many recent research projects have described typical chronic changes in the retinal vasculature for diverse neurovascular and neurodegenerative disorders such as stroke or Alzheimer's disease. Unlike cerebral vasculature, retinal blood vessels can be assessed non-invasively by retinal vessel analysis. To date, there is only a little information about potential simultaneous reactions of retinal and cerebral vessels in acute neurovascular diseases. The field of applications of retinal assessment could significantly be widened if more information about potential correlations between those two vascular beds and the feasibility of non-invasive retinal vessel analysis in acute neurovascular disease were available. Here, we present our protocol for the simultaneous assessment of retinal and cerebral vessels in an acute setting in anesthetized rats using a non-invasive retinal vessel analyzer and a superficial tissue imaging system for laser speckle contrast analysis via a closed bone window. We describe the experimental set-up in detail, outline the pitfalls of repeated retinal vessel analyses in an experimental set-up of several hours, and address issues that arise from the simultaneous use of two different assessment tools. Finally, we demonstrate the robustness and variability of the reactivity of retinal vessels to hypercapnia at baseline as well as their reproducibility over time using two anesthetic protocols common for neurovascular research. In summary, the procedures described in this protocol allow us to directly compare retinal and cerebral vascular beds and help to substantiate the role of the retina as a "window to the brain."
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Objectives: Prolactinomas represent the most common type of secreting pituitary adenomas, yet are rarely encountered in adolescent-onset (AO; i.e. <18 years) or elderly-onset (EO; i.e. ≥65 years) cohorts. As a result, it is not clear whether long-term strategies should be focused differently at both age extremes when comparing their therapeutic outcomes. We aimed at investigating long-term endocrinological outcomes, looking for differences between the two cohorts and evaluating the dependence on continued dopamine agonist (DA) therapy. Methods: Retrospective cross-sectional comparative study analyzing prolactinoma patients with a follow-up of ≥4 years. Clinical, radiological and biochemical characteristics were assessed at diagnosis and last follow-up. Longitudinal endocrinological outcomes between groups of extreme ages (i.e. AO and EO) and middle age (i.e. ≥18 years to 65 years) were compared. Independent risk factors for long-term dependence on DAs were calculated. Results: Follow-up at ≥4 years was recorded for 108 prolactinoma patients; 10 patients with AO and 10 patients with EO. Compared to AO patients, EO patients were predominantly men (p = 0.003), and presented with significantly higher prolactin (PRL) levels (p = 0.05) and higher body mass index (p = 0.03). We noted a significant positive correlation between patients' PRL values and their age (r = 0.5, p = 0.03) or BMI (r = 0.6, p = 0.03). After a median follow-up of 115 months, remission was noted in 87 (83%) patients; 9 (90%) in AO patients, and 7 (70%) in EO patients (p = 0.58). Continuation of DAs was required in 4 patients (40%) with AO and 7 patients (70%) with EO (p = 0.37). Patients with elderly-onset were an independent predictor of long-term dependence on DAs (HR 2.8, 95% CI 1.1-7.2, p = 0.03). Conclusions: Long-term control of hyperprolactinemia and hypogonadism does not differ between members of the AO and EO cohorts, and can be attained by the majority of patients. However, adjuvant DAs are often required, independent of the age of onset. Considering the clinical significance of persistent DA therapy for the control of hyperprolactinemia in many patients at both extremes of age, long-term monitoring may become recommended, in particular in patients with elderly-onset.
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BACKGROUND: Targeting a cerebral perfusion pressure optimal for cerebral autoregulation (CPPopt) has been gaining more attention to prevent secondary damage after acute neurological injury. Brain tissue oxygenation (PbtO2) can identify insufficient cerebral blood flow and secondary brain injury. Defining the relationship between CPPopt and PbtO2 after aneurysmal subarachnoid hemorrhage may result in (1) mechanistic insights into whether and how CPPopt-based strategies might be beneficial and (2) establishing support for the use of PbtO2 as an adjunctive monitor for adequate or optimal local perfusion. METHODS: We performed a retrospective analysis of a prospectively collected 2-center dataset of patients with aneurysmal subarachnoid hemorrhage with or without later diagnosis of delayed cerebral ischemia (DCI). CPPopt was calculated as the cerebral perfusion pressure (CPP) value corresponding to the lowest pressure reactivity index (moving correlation coefficient of mean arterial and intracranial pressure). The relationship of (hourly) deltaCPP (CPP-CPPopt) and PbtO2 was investigated using natural spline regression analysis. Data after DCI diagnosis were excluded. Brain tissue hypoxia was defined as PbtO2 <20 mmHg. RESULTS: One hundred thirty-one patients were included with a median of 44.0 (interquartile range, 20.8-78.3) hourly CPPopt/PbtO2 datapoints. The regression plot revealed a nonlinear relationship between PbtO2 and deltaCPP (P<0.001) with PbtO2 decrease with deltaCPP <0 mmHg and stable PbtO2 with deltaCPP ≥0mmHg, although there was substantial individual variation. Brain tissue hypoxia (34.6% of all measurements) was more frequent with deltaCPP <0 mmHg. These dynamics were similar in patients with or without DCI. CONCLUSIONS: We found a nonlinear relationship between PbtO2 and deviation of patients' CPP from CPPopt in aneurysmal subarachnoid hemorrhage patients in the pre-DCI period. CPP values below calculated CPPopt were associated with lower PbtO2. Nevertheless, the nature of PbtO2 measurements is complex, and the variability is high. Combined multimodality monitoring with CPP/CPPopt and PbtO2 should be recommended to redefine individual pressure targets (CPP/CPPopt) and retain the option to detect local perfusion deficits during DCI (PbtO2), which cannot be fulfilled by both measurements interchangeably.
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Lesões Encefálicas Traumáticas , Isquemia Encefálica , Hemorragia Subaracnóidea , Humanos , Estudos Retrospectivos , Oxigênio , Encéfalo/diagnóstico por imagem , Infarto Cerebral , Pressão Intracraniana , Circulação Cerebrovascular/fisiologia , Hipóxia , Lesões Encefálicas Traumáticas/diagnósticoRESUMO
Delayed cerebral ischemia (DCI) is a complication seen in patients with subarachnoid hemorrhage stroke. It is a major predictor of poor outcomes and is detected late. Machine learning models are shown to be useful for early detection, however training such models suffers from small sample sizes due to rarity of the condition. Here we propose a Federated Learning approach to train a DCI classifier across three institutions to overcome challenges of sharing data across hospitals. We developed a framework for federated feature selection and built a federated ensemble classifier. We compared the performance of FL model to that obtained by training separate models at each site. FL significantly improved performance at only two sites. We found that this was due to feature distribution differences across sites. FL improves performance in sites with similar feature distributions, however, FL can worsen performance in sites with heterogeneous distributions. The results highlight both the benefit of FL and the need to assess dataset distribution similarity before conducting FL.
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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.
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OBJECTIVE: To demonstrate the clinical outcome of patients with nonperimesencephalic subarachnoid hemorrhage (npSAH) compared with patients with aneurysmal SAH (aSAH) and perimesencephalic SAH (pSAH) and to evaluate predictive value of various clinical and radiological findings in patients with npSAH. METHODS: We retrospectively identified patients with SAH who presented at our institution between 2009 and 2018. We analyzed demographic and clinical data and outcomes. Multivariable analysis was performed for outcome parameters. RESULTS: Of 608 patients with confirmed SAH, 78% had aSAH, and 22% had nonaneurysmal SAH. Nonaneurysmal SAH was perimesencephalic in 30% of cases and nonperimesencephalic in 70%. Initial clinical status (Hunt and Hess score) was significantly worse in patients with aSAH compared with patients with nonaneurysmal SAH. Complications such as delayed cerebral ischemia occurred significantly more often in patients with aSAH. Patients with pSAH had a more favorable clinical course than patients with aSAH or npSAH. There was no significant difference in 30-day mortality between aSAH (29%) and npSAH (28%) patients (P = 0.835). Hunt and Hess score emerged as a strong predictor of unfavorable outcome in both aSAH and npSAH in multivariable regression. CONCLUSIONS: Patients with npSAH had a similar clinical outcome as patients with aSAH, although there were significantly fewer clinical complications in patients with npSAH. Patients with pSAH demonstrated an overall good clinical course. Our multivariable analysis showed that initial Hunt and Hess score was an important predictor for clinical outcome in aSAH as well as npSAH.
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Isquemia Encefálica , Hemorragia Subaracnóidea , Isquemia Encefálica/complicações , Infarto Cerebral/complicações , Humanos , Prognóstico , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/cirurgiaRESUMO
Objective: Outcome after aneurysmal subarachnoid hemorrhage (aSAH) is highly variable and largely determined by early brain injury and delayed cerebral ischemia (DCI). Soluble urokinase plasminogen activator receptor (suPAR) represents a promising inflammatory marker which has previously been associated with outcome in traumatic brain injury and stroke patients. However, its relevance in the context of inflammatory changes after aSAH is unclear. Here, we aimed to characterize the role of circulating suPAR in both serum and cerebrospinal fluid (CSF) as a novel biomarker for aSAH patients. Methods: A total of 36 aSAH patients, 10 control patients with unruptured abdominal aneurysm and 32 healthy volunteers were included for analysis. suPAR was analyzed on the day of admission in all patients. In aSAH patients, suPAR was also determined on the day of DCI and the respective time frame in asymptomatic patients. One- and two-sample t-tests were used for simple difference comparisons within and between groups. Regression analysis was used to assess the influence of suPAR levels on outcome in terms of modified Rankin score. Results: Significantly elevated suPAR serum levels (suPAR-SL) on admission were found for aSAH patients compared to healthy controls, but not compared to vascular control patients. Disease severity as documented according to Hunt and Hess grade and modified Fisher grade was associated with higher suPAR CSF levels (suPAR-CSFL). In aSAH patients, suPAR-SL increased daily by 4%, while suPAR-CSFL showed a significantly faster daily increase by an average of 22.5% per day. Each increase of the suPAR-SL by 1 ng/ml more than tripled the odds of developing DCI (OR = 3.06). While admission suPAR-CSFL was not predictive of DCI, we observed a significant correlation with modified Rankin's degree of disability at discharge. Conclusion: Elevated suPAR serum level on admission as a biomarker for early inflammation after aSAH is associated with an increased risk of DCI. Elevated suPAR-CSFL levels correlate with a higher degree of disability at discharge. These distinct relations and the observation of a continuous increase over time affirm the role of inflammation in aSAH and require further study.
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BACKGROUND: Dysfunctional cerebral autoregulation often precedes delayed cerebral ischemia (DCI). Currently, there are no data-driven techniques that leverage this information to predict DCI in real time. Our hypothesis is that information using continuous updated analyses of multimodal neuromonitoring and cerebral autoregulation can be deployed to predict DCI. METHODS: Time series values of intracranial pressure, brain tissue oxygenation, cerebral perfusion pressure (CPP), optimal CPP (CPPOpt), ΔCPP (CPP - CPPOpt), mean arterial pressure, and pressure reactivity index were combined and summarized as vectors. A validated temporal signal angle measurement was modified into a classification algorithm that incorporates hourly data. The time-varying temporal signal angle measurement (TTSAM) algorithm classifies DCI at varying time points by vectorizing and computing the angle between the test and reference time signals. The patient is classified as DCI+ if the error between the time-varying test vector and DCI+ reference vector is smaller than that between the time-varying test vector and DCI- reference vector. Finally, prediction at time point t is calculated as the majority voting over all the available signals. The leave-one-patient-out cross-validation technique was used to train and report the performance of the algorithms. The TTSAM and classifier performance was determined by balanced accuracy, F1 score, true positive, true negative, false positive, and false negative over time. RESULTS: One hundred thirty-one patients with aneurysmal subarachnoid hemorrhage who underwent multimodal neuromonitoring were identified from two centers (Columbia University: 52 [39.7%], Aachen University: 79 [60.3%]) and included in the analysis. Sixty-four (48.5%) patients had DCI, and DCI was diagnosed 7.2 ± 3.3 days after hemorrhage. The TTSAM algorithm achieved a balanced accuracy of 67.3% and an F1 score of 0.68 at 165 h (6.9 days) from bleed day with a true positive of 0.83, false positive of 0.16, true negative of 0.51, and false negative of 0.49. CONCLUSIONS: A TTSAM algorithm using multimodal neuromonitoring and cerebral autoregulation calculations shows promise to classify DCI in real time.
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Isquemia Encefálica , Hemorragia Subaracnóidea , Isquemia Encefálica/diagnóstico , Infarto Cerebral , Circulação Cerebrovascular/fisiologia , Humanos , Pressão IntracranianaRESUMO
BACKGROUND: First-line surgery for prolactinomas has gained increasing acceptance, but the indication still remains controversial. Thus, accurate prediction of unfavorable outcomes after upfront surgery in prolactinoma patients is critical for the triage of therapy and for interdisciplinary decision-making. OBJECTIVE: To evaluate whether contemporary machine learning (ML) methods can facilitate this crucial prediction task in a large cohort of prolactinoma patients with first-line surgery, we investigated the performance of various classes of supervised classification algorithms. The primary endpoint was ML-applied risk prediction of long-term dopamine agonist (DA) dependency. The secondary outcome was the prediction of the early and long-term control of hyperprolactinemia. METHODS: By jointly examining two independent performance metrics - the area under the receiver operating characteristic (AUROC) and the Matthews correlation coefficient (MCC) - in combination with a stacked super learner, we present a novel perspective on how to assess and compare the discrimination capacity of a set of binary classifiers. RESULTS: We demonstrate that for upfront surgery in prolactinoma patients there are not a one-algorithm-fits-all solution in outcome prediction: different algorithms perform best for different time points and different outcomes parameters. In addition, ML classifiers outperform logistic regression in both performance metrics in our cohort when predicting the primary outcome at long-term follow-up and secondary outcome at early follow-up, thus provide an added benefit in risk prediction modeling. In such a setting, the stacking framework of combining the predictions of individual base learners in a so-called super learner offers great potential: the super learner exhibits very good prediction skill for the primary outcome (AUROC: mean 0.9, 95% CI: 0.92 - 1.00; MCC: 0.85, 95% CI: 0.60 - 1.00). In contrast, predicting control of hyperprolactinemia is challenging, in particular in terms of early follow-up (AUROC: 0.69, 95% CI: 0.50 - 0.83) vs. long-term follow-up (AUROC: 0.80, 95% CI: 0.58 - 0.97). It is of clinical importance that baseline prolactin levels are by far the most important outcome predictor at early follow-up, whereas remissions at 30 days dominate the ML prediction skill for DA-dependency over the long-term. CONCLUSIONS: This study highlights the performance benefits of combining a diverse set of classification algorithms to predict the outcome of first-line surgery in prolactinoma patients. We demonstrate the added benefit of considering two performance metrics jointly to assess the discrimination capacity of a diverse set of classifiers.
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Hiperprolactinemia , Neoplasias Hipofisárias , Prolactinoma , Agonistas de Dopamina/uso terapêutico , Humanos , Aprendizado de Máquina , Neoplasias Hipofisárias/cirurgia , Prolactinoma/cirurgiaRESUMO
Introduction: There is no consensus in the treatment strategy of intracranial aneurysms (IAs) associated with brain arteriovenous malformation (BAVM). In particular, it is unknown if a more aggressive approach should be considered in patients harboring a BAVM, in whom multiple aneurysms or a history of aneurysmal subarachnoid hemorrhage (aSAH) is present. Case presentation: We report on an elderly woman harboring multiple aneurysms with a history of SAH due to rupture of an unrelated IA. On evaluation, she was also found to harbor a contralateral, left parietal convexity BAVM. Following resection of the latter, spontaneous regression of two large flow-related aneurysms was encountered. Discussion: We discuss the therapeutic decision-making, risk stratification, and functional outcome in this patient with regard to the pertinent literature on the risk of hemorrhage in IAs associated with BAVM.
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This study aims to investigate the characteristics of patients with mild aneurysmal and non-aneurysmal perimesencephalic and non-perimesencephalic subarachnoid hemorrhage (aSAH, pmSAH, npmSAH) with emphasis on admission biomarkers, clinical course, and outcome. A prospective cohort of 115 patients with aSAH (Hunt and Hess 1-3) and of 35 patients without aneurysms (16 pmSAH and 19 npmSAH) admitted between January 2014 and January 2020 was included. Demographic data, blood samples on admission, complications (hydrocephalus, shunt dependency, delayed cerebral ischemia DCI, DCI-related infarction, and mortality), and outcome after 6 months were analyzed. Demographic data was comparable between all groups except for age (aSAH 55 [48-65] vs. npmSAH 60 [56-68] vs. pmSAH 52 [42-60], p = 0.032) and loss of consciousness (33% vs. 0% vs. 0%, p = 0.0004). Admission biomarkers showed poorer renal function and highest glucose levels for npmSAH patients. Complication rate in npmSAH was high and comparable to that of aSAH patients (hydrocephalus, shunt dependency, DCI, DCI-related infarction, mortality), but nearly absent in patients with pmSAH. Favorable outcome after 6 months was seen in 92.9% of pmSAH, 83.3% of npmSAH, and 62.7% of aSAH (p = 0.0264). In this prospective cohort of SAH patients, npmSAH was associated with a complicated clinical course, comparable to that of patients with aSAH. In contrast, such complications were nearly absent in pmSAH patients, suggesting fundamental differences in the pathophysiology of patients with different types of non-aneurysmal hemorrhage. Our findings underline the importance for a precise terminology according the hemorrhage etiology as a basis for more vigilant management of npmSAH patients. NCT02142166, 05/20/2014, retrospectively registered.
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Aneurisma Intracraniano , Hemorragia Subaracnóidea , Idoso , Isquemia Encefálica/etiologia , Infarto Cerebral/etiologia , Estudos de Coortes , Humanos , Aneurisma Intracraniano/complicações , Pessoa de Meia-Idade , Estudos Prospectivos , Hemorragia Subaracnóidea/etiologiaRESUMO
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.
RESUMO
BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage negatively impacts long-term recovery but is often detected too late to prevent damage. We aim to develop hourly risk scores using routinely collected clinical data to detect DCI. METHODS: A DCI classification model was trained using vital sign measurements (heart rate, blood pressure, respiratory rate, and oxygen saturation) and demographics routinely collected for clinical care. Twenty-two time-varying physiological measures were computed including mean, SD, and cross-correlation of heart rate time series with each of the other vitals. Classification was achieved using an ensemble approach with L2-regularized logistic regression, random forest, and support vector machines models. Classifier performance was determined by area under the receiver operating characteristic curves and confusion matrices. Hourly DCI risk scores were generated as the posterior probability at time t using the Ensemble classifier on cohorts recruited at 2 external institutions (n=38 and 40). RESULTS: Three hundred ten patients were included in the training model (median, 54 years old [interquartile range, 45-65]; 80.2% women, 28.4% Hunt and Hess scale 4-5, 38.7% Modified Fisher Scale 3-4); 101 (33%) developed DCI with a median onset day 6 (interquartile range, 5-8). Classification accuracy before DCI onset was 0.83 (interquartile range, 0.76-0.83) area under the receiver operating characteristic curve. Risk scores applied to external institution datasets correctly predicted 64% and 91% of DCI events as early as 12 hours before clinical detection, with 2.7 and 1.6 true alerts for every false alert. CONCLUSIONS: An hourly risk score for DCI derived from routine vital signs may have the potential to alert clinicians to DCI, which could reduce neurological injury.
Assuntos
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Aprendizado de Máquina , Hemorragia Subaracnóidea/complicações , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Neurofisiológica , Fatores de RiscoRESUMO
BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is associated with arterial hypertension. Our aim was to investigate whether induced hypertension (IH) as therapy for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is associated with PRES and to identify risk factors for PRES. MATERIAL AND METHODS: We retrospectively searched our database for patients with SAH and IH in our institution between 2009 and 2018 and identified additional cases of PRES after SAH with IH from the literature. We then analyzed demographic findings and clinical features of these patients. RESULTS: 172 patients with acute SAH received IH. PRES was diagnosed in 3/172 (1.7%) patients. Our literature search revealed 17 additional cases. The pooled PRES group (n = 20) was non-significantly older than the non-PRES group (n = 169) (median, 62.5 years vs. 52 years, p = 0.06). No significant differences were found between both groups with regard to sex (p = 0.73), Hunt & Hess-Score (p = 0.9), aneurysm treatment (p = 0.13), and time from diagnosis of SAH to the start of IH (p = 0.14). CONCLUSIONS: PRES after IH in SAH patients occurred in 1.7% of our patients. Our results imply that it is important to be aware of a possible development of a PRES in older SAH patients with IH, irrespective of sex, initial clinical status, and treatment modality.