Rhinologic outcome of endoscopic transnasal-transsphenoidal pituitary surgery: an institutional series, systematic review, and meta-analysis

Purpose We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery. Methods Retrospective study on a consecutive cohort of treatment-naïve patients undergoing ETT pituitary gland surgery. Additionally, a systematic review and meta-analysis with focus on the rhinologic outcome, including postoperative smell function was performed. Results The institutional series incorporated 168 patients. A concomitant endoscopic septoplasty was performed in 29/168 patients (17.3%). A nasoseptal flap was used for reconstruction of large skull-base defects or high-flow CSF leaks in 4/168 (2.4%) patients. Early postoperative rhinologic complications (< 4 weeks) included epistaxis (3%), acute rhinosinusitis (1.2%) and late postoperative complications (≥ 8 weeks) comprised prolonged crusting (15.6%), symptomatic synechiae (11.9%) and septal perforation (0.6%). Postoperative smell function was not impaired (Fisher’s exact test, p = 1.0). The systematic review included 19 studies on 1533 patients with a median postoperative epistaxis rate of 1.4% (IQR 1.0–2.2), a postoperative acute rhinosinusitis rate of 2.3% (IQR 2.1–3.0), a postoperative synechiae rate of 7.5% (IQR 1.8–19.1) and a postoperative septal perforation rate of 2.2% (IQR 0.5–5.4). Seven studies including a total of 206 patients reported adequate outcome measures for smell function before and after ETT surgery. Only 2/7 studies reported an impairment of smell function postoperatively, especially in patients with nasoseptal flap harvesting. Conclusion Early and late postoperative rhinologic complication rates after ETT surgery for pituitary lesions seem to be low. A thorough evaluation of smell function, in particular in patients at risk for nasoseptal flap harvesting, may be an important factor in optimal postoperative care

Therapeutic Hypothermia Reduces Middle Cerebral Artery Flow Velocity in Patients with Severe Aneurysmal Subarachnoid Hemorrhage

Background: Transcranial Doppler (TCD) is widely used to detect and follow up cerebral vasospasm after subarachnoid hemorrhage (SAH). Therapeutic hypothermia might influence blood flow velocities assessed by TCD. The aim of the study was to evaluate the effect of hypothermia on Doppler blood flow velocity after SAH. Methods: In 20 patients treated with hypothermia (33°) due to refractory intracranial hypertension or delayed cerebral ischemia (DCI), mean flow velocity of the middle cerebral artery (MFVMCA) was assessed by TCD. Thirteen patients were treated with combined hypothermia and barbiturate coma and seven with hypothermia alone. MFVMCA was obtained within 24h before and after induction of hypothermia as well as before and after rewarming. Results: Hypothermia was induced on average 5days after SAH (range 1-12) and maintained for 144h (range 29-270). After hypothermia induction, MFVMCA decreased from 113.7±49.0 to 93.8±44.7cm/s (p=0.001). The decrease was independent of SAH-related complications and barbiturate coma. MFVMCA further decreased by 28.2cm/s between early and late hypothermia (p<0.001). This second decrease was observed in patients with DCI (p<0.001), but not in patients with intracranial hypertension (p=0.715). Compared to late hypothermia, MFVMCA remained unchanged after rewarming (65.6±32.1 vs 70.3±36.8cm/s; p=0.219). However, patients treated with hypothermia alone showed an increase in MFVMCA after rewarming (p=0.016). Conclusion: Therapeutic hypothermia after SAH decreases Doppler blood flow velocity in both intracranial hypertension and DCI cases. The results can be the effect of hypothermia-related mechanisms or resolving cerebral vasospasm during prolonged hypothermia

Endoscopic fenestration of intraventricular cerebrospinal fluid cysts: the contralateral approach

OBJECTIVE: The endoscopic fenestration of intraventricular CSF cysts has evolved into a well-accepted treatment modality. However, definition of the optimal trajectory for endoscopic fenestration may be difficult. Distorted ventricular anatomy and poor visibility within the cyst due to its contents can make endoscopic fenestration challenging if approached from the ipsilateral side. In addition, transcortical approaches can theoretically cause injury to eloquent cortex, particularly in patients with dominant-sided lesions. The aim of this study was to examine the value of the contralateral transcortical transventricular approach in patients with dominant-sided ventricular cysts. METHODS: During a 5-year period between 2007 and 2011, 31 patients with intraventricular CSF cysts underwent surgery by the senior author (R.R.). Fourteen of these patients had cysts located on the dominant side. An image-guided endoscopic cyst fenestration via the contralateral transcortical transventricular approach was performed in 11 patients. A retrospective chart review was performed in all these patients to extract data on clinical presentation, operative technique, and surgical outcome. RESULTS: The most common presenting symptom was headache, followed by memory deficits and cognitive deterioration. In all cases CSF cysts were space occupying, with associated obstructive hydrocephalus in 8 patients. Image-guided endoscopic fenestration was successfully performed in all cases, with septum pellucidotomy necessary in 6 cases, and endoscopic third ventriculostomy in 1 case for additional aqueductal occlusion. Postoperative clinical outcome was excellent, with no associated permanent neurological or neuropsychological morbidity. No recurrent cysts were observed over a mean follow-up period of 2 years and 3 months. CONCLUSIONS: The contralateral approach to ventricular cysts can achieve excellent surgical outcomes while minimizing approach-related trauma to the dominant hemisphere. Careful case selection is essential to ensure that the contralateral endoscopic trajectory is the best possible exposure for sufficient cyst fenestration and restoration of CSF circulation

Myocardial extracellular volume by T1 mapping: a new marker of arrhythmia in mitral valve prolapse.

We aimed to evaluate the relationship between mitral annular disjunction (MAD) severity and myocardial interstitial fibrosis at the left ventricular (LV) base in patients with mitral valve prolapse (MVP), and to assess the association between severity of interstitial fibrosis and the occurrence of ventricular arrhythmic events. In MVP, MAD has been associated with myocardial replacement fibrosis and arrhythmia, but the importance of interstitial fibrosis remains unknown. In this retrospective study, 30 patients with MVP and MAD (MVP-MAD) underwent cardiovascular magnetic resonance (CMR) with assessment of MAD length, late gadolinium enhancement (LGE), and basal segments myocardial extracellular volume (ECVsyn). The control group included 14 patients with mitral regurgitation (MR) but no MAD (MR-NoMAD) and 10 patients with normal CMR (NoMR-NoMAD). Fifteen MVP-MAD patients underwent 24 h-Holter monitoring. LGE was observed in 47% of MVP-MAD patients and was absent in all controls. ECVsyn was higher in MVP-MAD (30 ± 3% vs 24 ± 3% MR-NoMAD, p &lt; 0.001 and vs 24 ± 2% NoMR-NoMAD, p &lt; 0.001), even in MVP-MAD patients without LGE (29 ± 3% vs 24 ± 3%, p &lt; 0.001 and vs 24 ± 2%, p &lt; 0.001, respectively). MAD length correlated with ECVsyn (rho = 0.61, p &lt; 0.001), but not with LGE extent. Four patients had history of out-of-hospital cardiac arrest; LGE and ECVsyn were equally performant to identify those high-risk patients, area under the receiver operating characteristic (ROC) curve 0.81 vs 0.83, p = 0.84). Among patients with Holter, 87% had complex ventricular arrhythmia. ECVsyn was above the cut-off value in all while only 53% had LGE. Increase in ECVsyn, a marker of interstitial fibrosis, occurs in MVP-MAD even in the absence of LGE, and was correlated with MAD length and increased risk of out-of-hospital cardiac arrest. ECV should be includedin the CMR examination of MVP patients in an effort to better assess fibrous remodelling as it may provide additional value beyond the assessment of LGE in the arrhythmic risk stratification

Clinical potential of automated convolutional neural network-based hematoma volumetry after aneurysmal subarachnoid hemorrhage

Objectives Cerebrospinal fluid hemoglobin has been positioned as a potential biomarker and drug target for aneurysmal subarachnoid hemorrhage-related secondary brain injury (SAH-SBI). The maximum amount of hemoglobin, which may be released into the cerebrospinal fluid, is defined by the initial subarachnoid hematoma volume (ISHV). In patients without external ventricular or lumbar drain, there remains an unmet clinical need to predict the risk for SAH-SBI. The aim of this study was to explore automated segmentation of ISHV as a potential surrogate for cerebrospinal fluid hemoglobin to predict SAH-SBI. Methods This study is based on a retrospective analysis of imaging and clinical data from 220 consecutive patients with aneurysmal subarachnoid hemorrhage collected over a five-year period. 127 annotated initial non-contrast CT scans were used to train and test a convolutional neural network to automatically segment the ISHV in the remaining cohort. Performance was reported in terms of Dice score and intraclass correlation. We characterized the associations between ISHV and baseline cohort characteristics, SAH-SBI, ventriculoperitoneal shunt dependence, functional outcome, and survival. Established clinical (World Federation of Neurosurgical Societies, Hunt & Hess) and radiological (modified Fisher, Barrow Neurological Institute) scores served as references. Results A strong volume agreement (0.73 Dice, range 0.43 - 0.93) and intraclass correlation (0.89, 95% CI, 0.81-0.94) were shown. While ISHV was not associated with the use of antithrombotics or cardiovascular risk factors, there was strong evidence for an association with a lower Glasgow Coma Scale at hospital admission. Aneurysm size and location were not associated with ISHV, but the presence of intracerebral or intraventricular hemorrhage were independently associated with higher ISHV. Despite strong evidence for a positive association between ISHV and SAH-SBI, the discriminatory ability of ISHV for SAH-SBI was insufficient. The discriminatory ability of ISHV was, however, higher regarding ventriculoperitoneal shunt dependence and functional outcome at three-months follow-up. Multivariate survival analysis provided strong evidence for an independent negative association between survival probability and both ISHV and intraventricular hemorrhage. Conclusions The proposed algorithm demonstrates strong performance in volumetric segmentation of the ISHV on the admission CT. While the discriminatory ability of ISHV for SAH-SBI was similar to established clinical and radiological scores, it showed a high discriminatory ability for ventriculoperitoneal shunt dependence and functional outcome at three-months follow-up

MyD88-TLR4-dependent choroid plexus activation precedes perilesional inflammation and secondary brain edema in a mouse model of intracerebral hemorrhage

Background: The functional neurological outcome of patients with intracerebral hemorrhage (ICH) strongly relates to the degree of secondary brain injury (ICH-SBI) evolving within days after the initial bleeding. Different mechanisms including the incitement of inflammatory pathways, dysfunction of the blood–brain barrier (BBB), activation of resident microglia, and an influx of blood-borne immune cells, have been hypothesized to contribute to ICH-SBI. Yet, the spatiotemporal interplay of specific inflammatory processes within different brain compartments has not been sufficiently characterized, limiting potential therapeutic interventions to prevent and treat ICH-SBI. Methods: We used a whole-blood injection model in mice, to systematically characterized the spatial and temporal dynamics of inflammatory processes after ICH using 7-Tesla magnetic resonance imaging (MRI), spatial RNA sequencing (spRNAseq), functional BBB assessment, and immunofluorescence average-intensity-mapping. Results: We identified a pronounced early response of the choroid plexus (CP) peaking at 12–24 h that was characterized by inflammatory cytokine expression, epithelial and endothelial expression of leukocyte adhesion molecules, and the accumulation of leukocytes. In contrast, we observed a delayed secondary reaction pattern at the injection site (striatum) peaking at 96 h, defined by gene expression corresponding to perilesional leukocyte infiltration and correlating to the delayed signal alteration seen on MRI. Pathway analysis revealed a dependence of the early inflammatory reaction in the CP on toll-like receptor 4 (TLR4) signaling via myeloid differentiation factor 88 (MyD88). TLR4 and MyD88 knockout mice corroborated this observation, lacking the early upregulation of adhesion molecules and leukocyte infiltration within the CP 24 h after whole-blood injection. Conclusions: We report a biphasic brain reaction pattern after ICH with a MyD88-TLR4-dependent early inflammatory response of the CP, preceding inflammation, edema and leukocyte infiltration at the lesion site. Pharmacological targeting of the early CP activation might harbor the potential to modulate the development of ICH-SBI

Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity

Objectives: Cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin. Methods: DSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity. Results: DSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs -0.01 ± 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.0 ± 0.01), 45 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.01 ± 0.02) and 60 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.02 vs 0.01 ± 0.01). Conclusion: It is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH

Decongestion improving right heart function ameliorates prognosis after an acute heart failure episode.

The prognostic role of decongestion-related change of cardiac morphology and in particular right heart function has not been investigated comprehensively in AHF patients. This prospective observational single-centre study included consecutive patients hospitalized for treatment of AHF with reduced, mildly-reduced or preserved left ventricular ejection fraction (LVEF). Comprehensive transthoracic echocardiography at admission and discharge assessed decongestion-related change of cardiac function and morphology. The combined endpoint of 1 year all-cause mortality and cardiovascular rehospitalization explored the prognostic importance of decongestion-related change. The 176 study participants were 83 years old [74-87] and 54% were men. Fifty one (29%) had rLVEF, 65 (37%) mrLVEF, and 60 (34%) pLVEF. The proportion of de novo or worsening chronic HF was not different between LVEF groups. HF aetiology and cardiovascular risk factors were equally distributed across all groups except for a higher BMI in the pLVEF group. Decongestion equally reduced body weight, heart rate, systolic and diastolic blood pressure, tricuspid regurgitation gradient, and inferior vena cava diameter across all groups (P &lt; 0.004 for all). Decongestion-related increase in TAPSE independent of the LVEF was associated with improvement of right-ventricular-pulmonary artery coupling and a lower incidence of the combined outcome in the Cox proportional hazard risk analysis (unadjusted HR 0.50 95% CI 0.33-0.78, P = 0.002; adjusted HR 0.46 95% CI: 0.33-0.78, P = 0.001). Decongestion-related increase in TAPSE and recovery of RV/pulmonary artery coupling was observed across all LVEF groups and associated with a risk reduction for the combined endpoint highlighting the important prognostic role of right heart recovery after an AHF episode

The HeMoVal study protocol: a prospective international multicenter cohort study to validate cerebrospinal fluid hemoglobin as a monitoring biomarker for aneurysmal subarachnoid hemorrhage related secondary brain injury

Introduction: Preclinical studies provided a strong rationale for a pathophysiological link between cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) and secondary brain injury after subarachnoid hemorrhage (SAH-SBI). In a single-center prospective observational clinical study, external ventricular drain (EVD) based CSF-Hb proved to be a promising biomarker to monitor for SAH-SBI. The primary objective of the HeMoVal study is to prospectively validate the association between EVD based CSF-Hb and SAH-SBI during the first 14 days post-SAH. Secondary objectives include the assessment of the discrimination ability of EVD based CSF-Hb for SAH-SBI and the definition of a clinically relevant range of EVD based CSF-Hb toxicity. In addition, lumbar drain (LD) based CSF-Hb will be assessed for its association with and discrimination ability for SAH-SBI. Methods: HeMoVal is a prospective international multicenter observational cohort study. Adult patients admitted with aneurysmal subarachnoid hemorrhage (aSAH) are eligible. While all patients with aSAH are included, we target a sample size of 250 patients with EVD within the first 14 day after aSAH. Epidemiologic and disease-specific baseline measures are assessed at the time of study inclusion. In patients with EVD or LD, each day during the first 14 days post-SAH, 2 ml of CSF will be sampled in the morning, followed by assessment of the patients for SAH-SBI, co-interventions, and complications in the afternoon. After 3 months, a clinical follow-up will be performed. For statistical analysis, the cohort will be stratified into an EVD, LD and full cohort. The primary analysis will quantify the strength of association between EVD based CSF-Hb and SAH-SBI in the EVD cohort based on a generalized additive model. Secondary analyses include the strength of association between LD based CSF-Hb and SAH-SBI in the LD cohort based on a generalized additive model, as well as the discrimination ability of CSF-Hb for SAH-SBI based on receiver operating characteristic (ROC) analyses. Discussion: We hypothesize that this study will validate the value of CSF-Hb as a biomarker to monitor for SAH-SBI. In addition, the results of this study will provide the potential base to define an intervention threshold for future studies targeting CSF-Hb toxicity after aSAH

The HeMoVal study protocol: a prospective international multicenter cohort study to validate cerebrospinal fluid hemoglobin as a monitoring biomarker for aneurysmal subarachnoid hemorrhage related secondary brain injury.

INTRODUCTION Preclinical studies provided a strong rationale for a pathophysiological link between cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) and secondary brain injury after subarachnoid hemorrhage (SAH-SBI). In a single-center prospective observational clinical study, external ventricular drain (EVD) based CSF-Hb proved to be a promising biomarker to monitor for SAH-SBI. The primary objective of the HeMoVal study is to prospectively validate the association between EVD based CSF-Hb and SAH-SBI during the first 14 days post-SAH. Secondary objectives include the assessment of the discrimination ability of EVD based CSF-Hb for SAH-SBI and the definition of a clinically relevant range of EVD based CSF-Hb toxicity. In addition, lumbar drain (LD) based CSF-Hb will be assessed for its association with and discrimination ability for SAH-SBI. METHODS HeMoVal is a prospective international multicenter observational cohort study. Adult patients admitted with aneurysmal subarachnoid hemorrhage (aSAH) are eligible. While all patients with aSAH are included, we target a sample size of 250 patients with EVD within the first 14 day after aSAH. Epidemiologic and disease-specific baseline measures are assessed at the time of study inclusion. In patients with EVD or LD, each day during the first 14 days post-SAH, 2 ml of CSF will be sampled in the morning, followed by assessment of the patients for SAH-SBI, co-interventions, and complications in the afternoon. After 3 months, a clinical follow-up will be performed. For statistical analysis, the cohort will be stratified into an EVD, LD and full cohort. The primary analysis will quantify the strength of association between EVD based CSF-Hb and SAH-SBI in the EVD cohort based on a generalized additive model. Secondary analyses include the strength of association between LD based CSF-Hb and SAH-SBI in the LD cohort based on a generalized additive model, as well as the discrimination ability of CSF-Hb for SAH-SBI based on receiver operating characteristic (ROC) analyses. DISCUSSION We hypothesize that this study will validate the value of CSF-Hb as a biomarker to monitor for SAH-SBI. In addition, the results of this study will provide the potential base to define an intervention threshold for future studies targeting CSF-Hb toxicity after aSAH. STUDY REGISTRATION ClinicalTrials.gov Identifier NCT04998370 . Date of registration: August 10, 2021