The diagnostic yield of inferior petrosal sinus sampling in Cushing syndrome in the era of ovine CRH shortage.

PURPOSE: The ovine corticotropin-releasing hormone (oCRH) stimulation test has been routinely used in the diagnostic work-up of ACTH-dependent Cushing syndrome (CS). With oCRH currently being out-of-stock in Europe, we aimed at evaluating the diagnostic performance of inferior petrosal sinus sampling (IPSS) without oCRH stimulation. METHODS: We compared the values of 40 patients with ACTH-dependent CS and negative MRI findings in whom ACTH was measured before and after oCRH stimulation. RESULTS: The ratio of central-to-peripheral ACTH measurement (IPS:P) before the combined 3, 5, and 10 min of oCRH stimulation yielded diminished sensitivity (85% vs. 97%), alongside markedly decreased specificity (57% vs. 71%), as well as reduced positive and negative predictive values (90% vs. 94% and 44% vs. 83%), respectively. CONCLUSIONS: With the current drug shortages in Europe, ACTH measurements without oCRH stimulation in IPSS cannot be recommended. Thus, we call for desmopressin or the commercially available human CRH as a potential alternative in the confirmation of ACTH excess by IPSS in equivocal MRI findings.

Cannabinoids for Acute Pain Management: Approaches and Rationale.

PURPOSE OF THE REVIEW: Acute pain management remains a challenge and postoperative pain is often undermanaged despite many available treatment options, also including cannabinoids. RECENT FINDINGS: In the light of the opioid epidemic, there has been growing interest in alternative care bundles for pain management, including cannabinoids as potential treatment to decrease opioid prescribing. Despite the lack of solid evidence on the efficacy of cannabinoids, their use among patients with pain, including those using opioids, is currently increasing. This use is supported by data suggesting that cannabinoids could potentially contribute to a better pain management and to a reduction in opioid doses while maintaining effective analgesia with minimum side effects. The scientific basis for supporting the use of cannabis is extensive, although it does not necessarily translate into relevant clinical outcomes. The use of cannabinoids in acute pain did not always consistently show statistically significant results in improving acute pain. Large randomized, controlled trials evaluating diverse cannabis extracts are needed in different clinical pain populations to determine safety and efficacy.

Nerve Blocks for Craniotomy.

PURPOSE OF REVIEW: Postcraniotomy headache (PCH) is a common adverse event and can lead to various complications and decreased quality of life. RECENT FINDINGS: To reduce postcraniotomy pain and associated complications, a multimodal pain therapy including analgesics, analgesic adjuncts, and regional anesthesia is essential. The use of opioids should be minimized to facilitate prompt postoperative neurosurgical assessment. Here, we provide an update on the latest evidence regarding the role of scalp nerve blocks in the pain management of patients undergoing craniotomy procedure. Nerve blocks are effective in alleviating postoperative pain after craniotomy. Scalp blocks contribute to lower pain levels and less opioid consumption in the first 48 h following surgery. Moreover, there is a significant decrease in patients suffering from PONV among patients who receive scalp block.

Gender-specific prolactin thresholds to determine prolactinoma size: a novel Bayesian approach and its clinical utility.

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 239.4 µg/L (95% credible interval: 44.0-451.2 µg/L) to discriminate between micro- and macroadenomas. We find evidence of gender-specific prolactin thresholds of 211.6 µg/L (95% credible interval: 29.0-426.2 µg/L) for women and 1,046.1 µg/L (95% credible interval: 582.2-2,325.9 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.

Safety and functional outcome analysis of ventriculoperitoneal shunt placement for hydrocephalus within the critical phase of possible delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

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.

Topographic distribution of inflammation factors in a healing aneurysm.

BACKGROUND: Healing of intracranial aneurysms following endovascular treatment relies on the organization of early thrombus into mature scar tissue and neointima formation. Activation and deactivation of the inflammation cascade plays an important role in this process. In addition to timely evolution, its topographic distribution is hypothesized to be crucial for successful aneurysm healing. METHODS: Decellularized saccular sidewall aneurysms were created in Lewis rats and coiled. At follow-up (after 3 days (n = 16); 7 days (n = 19); 21 days (n = 8)), aneurysms were harvested and assessed for healing status. In situ hybridization was performed for soluble inflammatory markers (IL6, MMP2, MMP9, TNF-α, FGF23, VEGF), and immunohistochemical analysis to visualize inflammatory cells (CD45, CD3, CD20, CD31, CD163, HLA-DR). These markers were specifically documented for five regions of interest: aneurysm neck, dome, neointima, thrombus, and adjacent vessel wall. RESULTS: Coiled aneurysms showed enhanced patterns of thrombus organization and neointima formation, whereas those without treatment demonstrated heterogeneous patterns of thrombosis, thrombus recanalization, and aneurysm growth (p = 0.02). In coiled aneurysms, inflammation markers tended to accumulate inside the thrombus and in the neointima (p < 0.001). Endothelial cells accumulated directly in the neointima (p < 0.0001), and their presence was associated with complete aneurysm healing. CONCLUSION: The presence of proinflammatory cells plays a crucial role in aneurysm remodeling after coiling. Whereas thrombus organization is hallmarked by a pronounced intra-thrombotic inflammatory reaction, neointima maturation is characterized by direct invasion of endothelial cells. Knowledge concerning topographic distribution of regenerative inflammatory processes may pave the way for future treatment modalities which enhance aneurysm healing after endovascular therapy.

Acute Pain and Development of Opioid Use Disorder: Patient Risk Factors.

PURPOSE OF REVIEW: Pharmacological therapy for acute pain carries the risk of opioid misuse, with opioid use disorder (OUD) reaching epidemic proportions worldwide in recent years. This narrative review covers the latest research on patient risk factors for opioid misuse in the treatment of acute pain. In particular, we emphasize newer findings and evidence-based strategies to reduce the prevalence of OUD. RECENT FINDINGS: This narrative review captures a subset of recent advances in the field targeting the literature on patients' risk factors for OUD in the treatment for acute pain. Besides well-recognized risk factors such as younger age, male sex, lower socioeconomic status, White race, psychiatric comorbidities, and prior substance use, additional challenges such as COVID-19 further aggravated the opioid crisis due to associated stress, unemployment, loneliness, or depression. To reduce OUD, providers should evaluate both the individual patient's risk factors and preferences for adequate timing and dosing of opioid prescriptions. Short-term prescription should be considered and patients at-risk closely monitored. The integration of non-opioid analgesics and regional anesthesia to create multimodal, personalized analgesic plans is important. In the management of acute pain, routine prescription of long-acting opioids should be avoided, with implementation of a close monitoring and cessation plan.

Anatomical distribution and clinical significance of middle cerebral artery M2 segment vessel occlusions and its cortical branches in acute ischaemic stroke patients.

Background: Characterisation of anatomical distribution and the clinical impact of middle cerebral artery M2 (MCA-M2) segment occlusion and its subsequent cortical branches (CBs) in acute ischaemic stroke patients (AIS). Methods: Retrospective, monocentric study analysing radiological and clinical data of AIS patients with MCA-M2 segment occlusion with regard to the anatomic distribution of MCA-M2 occlusion and its subsequent CB. Results: A total of 203 patients (median age 77 (IQR 66-83) years, 112 women) were included. There was an equal distribution of right-sided versus left-sided MCA-M2 vessel occlusions (right: n=97; left: n=106), as well as with a median number of affected MCA-M2 CBs of 4 (IQR, 3-6) and a median National Institute of Health Stroke Scale score (NIHSS) on admission of 9 (3-15). For both hemispheres, CBs of the inferior trunks were significantly more affected than the superior trunks. Endovascular treatment (EVT, n=94) was associated with a significant better outcome compared with patients with medical management alone (p=0.027). Conclusion: In acute MCA-M2 segment occlusions, inferior trunks are significantly more affected compared with the superior trunks. The subsequent CBs of the paracentral region of both hemispheres are more commonly involved. In eloquent vascular territories, EVT was more often performed.

Meditation as an Adjunct to the Management of Acute Pain.

PURPOSE OF REVIEW: We aim to present current understanding and evidence for meditation, mostly referring to mindfulness meditation, for the management of acute pain and potential opportunities of incorporating it into the acute pain service practice. RECENT FINDINGS: There is conflicting evidence concerning meditation as a remedy in acute pain. While some studies have found a bigger impact of meditation on the emotional response to a painful stimulus than on the reduction in actual pain intensities, functional Magnet Resonance Imaging has enabled the identification of various brain areas involved in meditation-induced pain relief. Potential benefits of meditation in acute pain treatment include changes in neurocognitive processes. Practice and Experience are necessary to induce pain modulation. In the treatment of acute pain, evidence is emerging only recently. Meditative techniques represent a promising approach for acute pain in various settings.

A Diagnostic Biomarker for Cervical Myelopathy Based on Dynamic Magnetic Resonance Imaging.

STUDY DESIGN: Multicenter prospective observational study. OBJECTIVE: Diffusion tensor imaging in flexion extension improves the diagnosis of degenerative cervical myelopathy (DCM). We aimed to provide an imaging biomarker for the detection of DCM. SUMMARY OF BACKGROUND DATA: DCM is the most common form of spinal cord dysfunction in adults; however, imaging surveillance for myelopathy remains poorly characterized. PATIENTS AND METHODS: Symptomatic DCM patients were examined in maximum neck flexion-extension and neutral positions in a 3T-magnetic resonance imaging scanner and allocated to 2 groups: (1) Patients with visible intramedullary hyperintensity (IHIS) on T2-weighted imaging (IHIS+, n = 10); and (2) Patients without IHIS (IHIS-, n = 11). Range of motion, space available for the spinal cord, apparent diffusion coefficient (ADC), axial diffusivity (AD), radial diffusivity, and fractional anisotropy were measured and compared between the neck positions and between the groups as well as between control (C2/3) and pathologic segments. RESULTS: Significant differences between the control level (C2/3) and pathologic segments were appreciated for the IHIS+ group at neutral neck position in AD; at flexion in ADC and AD; and at neck extension in ADC, AD, and fractional anisotropy values. For the IHIS- group, significant differences between the control level (C2/3) and pathologic segments were found only for ADC values in neck extension. When comparing diffusion parameters between groups, radial diffusivity was significantly different in all 3 neck positions. CONCLUSION: Significant increases in ADC values between the control and pathologic segments were found for both groups in neck extension only. This may serve as a diagnostic tool to identify early changes in the spinal cord related to myelopathy to indicate potentially reversible spinal cord injury and support the indication for surgery in select circumstances.

Prolactinomas in adolescent and elderly patients-A comparative long-term analysis.

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.

Anatomical Variations of the Common Carotid Arteries and Neck Structures of the New Zealand White Rabbit and Their Implications for the Development of Preclinical Extracranial Aneurysm Models.

BACKGROUND: Rabbit models involving neck arteries are of growing importance for the development of preclinical aneurysm models. An optimal understanding of the anatomy is primordial to allow the conception of models while minimizing mortality and morbidity. The aim of this study is to give reliable anatomical landmarks to allow a standardized approach to the neck vessels. METHODS: We performed a necropsy on nine specimens from ongoing experimental studies. We measured the distance between the origins of the right and left common carotid artery (rCCA/lCCA) and between the rCCA and the manubrium sterni (MS). The structures at risk were described. RESULTS: Female New Zealand White rabbits (NZWR) weighing 3.7 ± 0.3 kg and aged 25 ± 5 weeks were included. The rCCA origin was located 9.6 ± 1.2 mm laterally and 10.1 ± 3.3 mm caudally to the MS. In all specimens, the lCCA originated from the aortic arch, together with the brachiocephalic trunk (BCT), and 6.2 ± 3.1 mm proximally to the rCCA origin. The external and internal jugular veins, trachea and laryngeal nerve were the main structures at risk. CONCLUSIONS: The data help to localize both CCAs and their origin to guide surgical approaches with the manubrium sterni as a main landmark. Special attention has to be paid to the trachea, jugular veins and laryngeal nerves.

Risk of intracranial aneurysm recurrence after microsurgical clipping based on 3D digital subtraction angiography.

OBJECTIVE: Current knowledge of recurrence rates after intracranial aneurysm (IA) surgery relies on 2D digital subtraction angiography (DSA), which fails to detect more than 75% of small aneurysm remnants. Accordingly, the discrimination between recurrence and growth of a remnant remains challenging, and actual assessment of recurrence risk of clipped IAs could be inaccurate. The authors report, for the first time, 3D-DSA-based long-term durability and risk factor data of IA recurrence and remnant growth after microsurgical clipping. METHODS: Prospectively collected data for 305 patients, with a total of 329 clipped IAs that underwent baseline 3D-DSA, were evaluated. The incidence of recurrent IA was described by Kaplan-Meier curves. Risk factors for IA recurrence were analyzed by multivariable Cox proportional hazards and logistic regression models. RESULTS: The overall observed proportion of IA recurrence after clipping was 2.7% (9 of 329 IAs) at a mean follow-up of 46 months (0.7% per year). While completely obliterated IAs did not recur during follow-up, incompletely clipped aneurysms (76 of 329) demonstrated remnant growth in 11.8% (3.4% per year). Young age and large initial IA size significantly increased the risk of IA recurrence. CONCLUSIONS: The findings support those in previous studies that hypothesized that completely clipped IAs have an extremely low risk of recurrence. Conversely, the results highlight the significant risk posed by incompletely clipped IAs. Young patients with initial large IAs and incomplete obliteration have an especially high risk for IA recurrence and therefore should be monitored more closely.

Growing Fat Tissue After Grafting for Dural Sealing.

We report on a young patient with a growing retroauricular benign fat tissue tumor after juvenile fat grafting for dural sealing of a placed ventriculoperitoneal shunt. The clinical images indicate fat tissue rather than a cerebrospinal fluid leak due to potential shunt malfunction suspected on plain radiography. Human adipose tissue is a source of stem cells that can replicate rather than undergoing necrosis, in particular when transplanted during development.

Incidence and Outcome of Peri-interventional Vasospasm During Endovascular or Microsurgical Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND: Peri-interventional vasospasm (PIVS) is associated with high risk of delayed cerebral vasospasm (DCVS), delayed cerebral ischemia, and poor outcome after aneurysmal subarachnoid hemorrhage. However, the incidence rate associated with treatment of unruptured intracranial aneurysm (UIA) remains unclear. OBJECTIVE: To define the incidence and clinical significance of PIVS in UIA repair based on intraoperative/peri-interventional digital subtraction angiography. METHODS: A consecutive series of 205 patients who underwent UIA treatment by means of microsurgical clipping (n = 109) or endovascular coil embolization (n = 96) was assessed for the occurrence of PIVS. In all cases, PIVS was detected, measured, and classified using intraoperative/peri-interventional digital subtraction angiography. Severity of PIVS, association of PIVS with the development of DCVS, and neurological outcome were analyzed. RESULTS: Intraoperative PIVS was present in n = 14/109 (13%) patients with microsurgical clipping. Of these, caliber irregularities were mild (n = 10), moderate (n = 3), and severe (n = 1). In endovascularly treated patients, 6/96 (6%) developed PIVS, which were either mild (n = 3) or moderate (n = 3). Management in all cases included immediate intensive blood pressure management and application of topical papaverine or intra-arterial nimodipine immediately on detection of PIVS. No patient developed DCVS or lasting neurological deficits attributable to PIVS. CONCLUSION: This series revealed a relatively high overall incidence of PIVS (10%). However, no association of PIVS with the development of DCVS or poor outcome was found. In contrast to ruptured intracranial aneurysms, PIVS in unruptured intracranial aneurysms-if immediately and adequately addressed-seems to be benign and without sequelae for patient's functional outcome.

The Effect of Losartan on Neuroinflammation as Well as on Endothelin-1- and Serotonin-Induced Vasoconstriction in a Double-Haemorrhage Rat Model.

Poor patient outcome after aneurysmal subarachnoid haemorrhage (SAH) is due to a multifactorial process. Delayed cerebral vasospasm, ischemic neurological deficits, and infarction are the most feared acute sequelae triggered by enhanced synthesis of serotonin and endothelin-1 (ET-1). During the past decades, multiple drugs have been analysed for protective effects without resounding success. Therefore, the authors wanted to analyse the potential beneficial role of Losartan (LOS). Male Sprague Dawley rats were randomised into either a group receiving two injections of blood into the cisterna magna (SAH group) or a group receiving two injections of isotonic sodium chloride (sham group). The animals were culled on day five and basilar artery ring segments were used for in vitro tension studies. Sarafotoxin S6c caused a dose-dependent vasorelaxation in sham and SAH segments, which was more pronounced in sham segments. LOS, applied in a concentration of 10−3 M, was able to significantly reduce serotonin- (p < 0.01) and ET-1- (p < 0.05, p < 0.01) mediated vasoconstriction in sham segments. These findings, along with the well-known beneficial effects of LOS on restoring the impaired endothelin-B1-receptor function after SAH, as well as on the neuroprotectional and antiepileptogenic aspects, might be implemented in advancing tailored concepts to sufficiently ameliorate patients' functional outcome after SAH.