Atkinson, John L. D.

BACKGROUND AND OBJECTIVES: Venous air embolism (VAE) can cause significant morbidity and mortality. Prevention and management of VAE include cessation of air entrainment, positioning changes, and hemodynamic support. The degree to which position change and cardiac output (CO) moderate resolution of intracardiac air has not been rigorously studied using contemporary transesophageal echocardiography (TEE). METHODS: This observational cohort-type study aimed to identify the effect of supine vs sitting positioning on the movement and resolution of intracardiac air. In 20 patients undergoing seated neurosurgery, central venous air aspiration catheters were placed through the median basilic vein. TEE was used to estimate the time required for clearance of agitated microbubbles from the right atrium and ventricle in both the supine and sitting position. Estimates of CO were also obtained echocardiographically in each position. RESULTS: Average clearance time was faster in the sitting vs the supine position with no significant difference in CO. A negative correlation between CO and right atrial clearance time across all patients was demonstrated with a Pearson coefficient of −0.4 (95% CI −0.07, −0.65) with P = .02. CONCLUSION: During VAE, both patient position and CO can significantly affect how bubbles move through intracardiac chambers. However, augmenting CO during VAE may be clinically more feasible, efficient, and productive than changing positioning—especially during crises unless the changing in position is intended to halt the entrainment of air. Further TEE studies of intravascular air movement affected by other position changes (lateral, reverse Trendelenburg) and vasopressors should be considered.

OBJECTIVE Nonfunctioning pituitary adenomas (NFPAs) present at a wide range of ages; it is possible that variable outcomes are based on patient age at presentation. This study aimed to explore long-term outcomes of patients with NFPAs following endonasal transsphenoidal surgery (ETS), considering age stratification. METHODS This retrospective study included 228 patients with NFPAs who underwent ETS, with a median follow-up period of 63 months. The outcomes included progression-free survival (PFS) rates and neurological and endocrinological outcomes. Age-stratified Kaplan-Meier and Cox proportional hazards analyses were performed. Patients were classified into four age groups: ≤ 49, 50–59, 60–69, and ≥ 70 years. RESULTS Age-stratified analysis showed a significant correlation between age and PFS in NFPAs (5-year PFS rates: 63.0% in those ≤ 49 years, 76.7% in those 50–59 years, 85.0% in those 60–69 years, and 88.1% in those ≥ 70 years; p = 0.001, log-rank test). Bivariate (HR 1.03, 95% CI 1.01–1.05; p = 0.001) and multivariable (HR 1.03, 95% CI 1.02–1.05; p = 0.001) analyses demonstrated that older age was significantly associated with longer PFS. Multivariable analysis also demonstrated that smaller maximum tumor diameter (HR 0.77, 95% CI 0.60–0.99; p = 0.036) and gross-total resection (HR 8.55, 95% CI 3.90–18.75; p = 0.001) were significantly associated with longer PFS. Multivariable logistic regression analysis demonstrated that only younger age was associated with postoperative improvement of male hypogonadism (HR 0.91, 95% CI 0.84–0.99; p = 0.019). Other postoperative neurological and endocrinological outcomes were not significantly associated with age. CONCLUSIONS Older patients with NFPAs treated with ETS demonstrated a longer PFS. Of endocrinological outcomes studied, only male hypogonadism improvement was associated with younger patient age.

OBJECTIVE Arginine vasopressin deficiency (AVD) following neurosurgical procedures for pituitary disorders is common and can delay discharge. Copeptin, a stable surrogate marker of arginine vasopressin, may predict postoperative AVD. The authors’ aim was to assess the optimal postoperative sampling time and cut-point concentration of copeptin to predict the development of postsurgical AVD. METHODS Adults without preexisting AVD who were undergoing surgery for a pituitary lesion between February 2020 and April 2022 were eligible for study inclusion. Two samples were drawn from each patient postoperatively to assess the copeptin concentration using an immunofluorescent assay. Samples were denoted as "early" (within 6 hours of extubation) or "postoperative day 1" (POD1; within 10–30 hours of extubation). Patients were evaluated for the development of AVD. RESULTS One hundred ninety-two patients (54.2% female) with a median age of 54.5 years (IQR 39.8–67.0 years) were included in the study. The median copeptin concentration at both time points was significantly lower in those with AVD (transient or permanent; n = 22, 11.5%) than in those without (early: 4.9 vs 18.7 pmol/L, p < 0.001; POD1: 3.4 vs 4.9 pmol/L, p < 0.001) but did not differ in those who developed transient versus permanent AVD. The optimal copeptin cut point for the prediction of AVD was < 8.5 pmol/L for early samples (sensitivity 0.70, specificity 0.80, positive predictive value [PPV] 0.29, negative predictive value [NPV] 0.96) and < 4.3 pmol/L for POD1 samples (sensitivity 0.82, specificity 0.63, PPV 0.22, NPV 0.96). In early samples, a copeptin cutoff of 22.9 pmol/L increased the sensitivity for the detection of AVD to 95% with an NPV of 99%. The proportion of patients who had AVD was higher (60.0% vs 8.8%, p < 0.001) and the copeptin concentration lower (early: 4.3 vs 17.0 pmol/L, p < 0.001; POD1: 2.7 vs 4.9 pmol/L, p < 0.001) among those who had undergone surgery for a craniopharyngeal duct pathology versus a pituitary adenoma. Although copeptin was lower in patients with persistent Cushing’s disease than in those in remission, the difference did not reach statistical significance (early p = 0.11, POD1 p = 0.52). Furthermore, the copeptin concentration could not predict the development of syndrome of inappropriate secretion of antidiuretic hormone. Patients without AVD who had received stress dose steroids intraoperatively had lower median early copeptin (11.7 vs 19.1 pmol/L, p = 0.027). CONCLUSIONS In early postoperative copeptin samples, the optimal copeptin cut point for AVD diagnosis was < 8.5 pmol/L, and a level > 22.9 pmol/L had predicative utility in excluding AVD. Caution should be used when interpreting copeptin results, as patients administered glucocorticoids intraoperatively without AVD had lower median copeptin concentrations.

Background Cerebrospinal fluid-venous fistulas (CSFVF) are a common cause of spontaneous intracranial hypotension (SIH). Transvenous embolization has emerged as a reliable treatment option. We review the clinical presentation, imaging, and clinical outcomes of 100 consecutive CSFVF patients who underwent embolization over 2 years. Methods Baseline clinical characteristics, imaging findings (including Bern SIH score), technical outcomes, and long-term imaging and clinical outcomes were collected. All patients had at least 3 months of clinical follow-up and had baseline MRI. 99/100 patients underwent follow-up imaging at ≥3 months post-treatment. Results 100 patients were included. Mean imaging and clinical follow-up duration was 8.3±7.7 months and 15.0±6.8 months, respectively. The mean duration of symptoms before embolization was 40.9±52 months. Mean baseline Bern SIH score was 5.9±3.3. The most common baseline symptoms were headache (96 patients), tinnitus (55 patients), and cognitive dysfunction (44 patients). Technical success rate was 100%. Mean post-treatment Bern SIH score was 0.9±1.6 (P<0.0001). Following treatment, 95% of patients reported significant improvement or resolution in symptoms (58 patients reporting resolution and 37 reporting improvement). 5 patients reported no improvement. There were no major procedural or periprocedural complications. 10 patients had minor procedural complications that did not result in any change in management (Onyx emboli, venous perforation). 19 patients had rebound intracranial hypertension requiring acetazolamide therapy. 7 patients had recurrent fistula at the initially treated level. Conclusions Transvenous embolization of CSFVF in SIH patients is safe and effective with a 95% treatment response, significant improvement in imaging outcomes, and a very low rate of complications.

OBJECTIVE Malignant melanotic nerve sheath tumors are rare tumors characterized by neoplastic melanin-producing Schwann cells. In this study, the authors report their institution’s experience in treating spinal and peripheral malignant melanotic nerve sheath tumors and compare their results with the literature. METHODS Data were collected from 8 patients who underwent surgical treatment for malignant melanotic nerve sheath tumors between 1996 and 2023 at Mayo Clinic and 63 patients from the literature. Time-to-event analyses were performed for the combined group of 71 cases to evaluate the risk of recurrence, metastasis, and death based on tumor location and type of treatment received. Unpaired 2-sample t-tests and Fisher’s exact tests were used to determine statistical significance between groups. RESULTS Between 1996 and 2023, 8 patients with malignant melanotic nerve sheath tumors underwent surgery at the authors’ institution, while 63 patients were identified in the literature. The authors’ patients and those in the literature had the same mean age at diagnosis (43 years). At the authors’ institution, 5 patients (63%) experienced metastasis, 6 patients (75%) experienced long-term recurrence, and 5 patients (62.5%) died. In the literature, most patients (60.3%) were males, with a peak incidence between the 4th and 5th decades of life. Nineteen patients (31.1%) were diagnosed with Carney complex. Nerve root tumors accounted for most presentations (n = 39, 61.9%). Moreover, 24 patients (38.1%) had intradural lesions, with 54.2% (n = 13) being intramedullary and 45.8% (n = 11) extramedullary. Most patients underwent gross-total resection (GTR) (n = 41, 66.1%), followed by subtotal resection (STR) (n = 12, 19.4%), STR with radiation therapy (9.7%), and GTR with radiation therapy (4.8%). Sixteen patients (27.6%) experienced metastasis, 23 (39.7%) experienced recurrence, and 13 (22%) died. Kaplan-Meier analyses showed no significant differences among treatment approaches in terms of recurrence-free, metastasis-free, and overall survival (p > 0.05). Similar results were obtained when looking at the differences with respect to intradural versus nerve root location of the tumor (p > 0.05). CONCLUSIONS Malignant melanotic nerve sheath tumors are rare tumors with a high potential for malignancy. They carry a dismal prognosis, with a pooled local recurrence rate of 42%, distant metastasis rate of 27%, and mortality rate of 26%. The findings from this study suggest a trend favoring the use of GTR alone or STR with radiation therapy over STR alone. Mortality was similar regardless, which highlights the need for the development of effective treatment options to improve survival in patients with melanotic schwannomas.

Abstract Disclosure: D.Z. Erickson: None. D. Donegan: None. J. Van Gompel: None. J. Atkinson: None. M. Link: None. F. Meyer: None. M. Peris-Celda: None. G. Spears: None. J. Bornhorst: None. M. Hoplin: None. Dysnatremias are common after neurosurgical procedures. Depending on the cohort assessed, transient arginine vasopressin deficiency (AVD) following neurological procedures is seen in up to 46% of patients which can delay discharge. Copeptin (COPEP), a stable surrogate marker of arginine vasopressin, has demonstrated utility in the prediction of postoperative AVD, however COPEP cutoff and sample timing has varied. Aim: To assess the optimal sampling time and cut point concentration of COPEP to predict the development of post-surgical AVD. Method: Adults who had transsphenoidal surgery (TSS) for a sellar or suprasellar mass between February 2020 and April 2022 without pre-existing AVD were prospectively enrolled if agreeable. Two COPEP samples (immunofluorescent assay on B.R.A.H.M.S Kryptor Compact PLUS) included “early” sample 1-6 hours following extubation, and another post-op day 1 (POD1, 10-30 hours of extubation). Patients were assessed for the development of AVD; defined as new onset hypotonic (&lt; 295 mmol/kg) polyuria (&gt;50 ml/kg/d) without other causes. Patient demographics and tumor characteristics were collected. Results: 192 patients (median age 54.5 (39.8-67.0) years with 54.2% female) were included. Surgical indications included non-functioning pituitary adenoma (N=101), functioning pituitary adenoma (N= 78), disorders or the craniopharyngeal duct (N=10) and other (N=3). Median COPEP levels were associated with age, but not sex. Median COPEP levels were significantly lower at both time points in patients who developed AVD (N=20, 10.4%) vs those who did not, (early: 4.9 vs 18.7 pmol/L, P= &lt;0.001; POD1: 3.35 vs 4.9 pmol/L, P=&lt;0.001). Change in median COPEP level between the 2 sample times was lower in those who developed AVD -1.8 pmol/L vs who did not -12.6 pmol/L (P&lt;0.001). ROC curve analysis of early COPEP indicated that a level &gt;20.3 pmol/L had a negative predictive value (NPV) of 97% whereas POD1 level &gt;6.7 pmolL had a NPV of 96%. In univariate logistic analysis, lower early COPEP was associated with higher risk of AVD (OR=0.34, CI 0.26 -0.62, p=0.008), with an optimal cut point of 8.5 pmol/L. A similar association was seen for POD1 COPEP (OR=0.19, CI 0.07- 0.53, p= 0.002), which had an optimal cut point of 4.3 pmol/L. In patients with disorders of the craniopharyngeal system vs those who had TSS for other reasons, AVD was more common (60% vs 9%, P&lt;0.001) and median COPEP levels were lower at both time points. Those without AVD who received stress dose steroids intraoperatively had lower median early COPEP (11.7 vs 19.1 pmol/L, P=0.27). Conclusion: In early samples taken following extubation, the optimal COPEP cut point for AVD diagnosis was 8.5 pmol/L and a level of &gt;20.3 pmol/L has predicative utility in excluding AVD. However, caution should be used in patients who are administered glucocorticoids intra-operatively as this was associated with a lower median COPEP level. Presentation: Thursday, June 15, 2023

OBJECTIVE Inferior petrosal sinus (IPS) sampling (IPSS) is a diagnostic procedure used to guide diagnostic localization of imaging-negative adrenocorticotropic hormone (ACTH)–secreting pituitary microadenomas. However, the efficacy of IPSS has been suboptimal at accurately lateralizing the adenoma, reducing surgical cure rates and leading to unintended pituitary dysfunction due to the added exploration. One rationale for the occasional imprecision is the existence of additional petrosal sinus collateral channels that connect the IPS bilaterally, which may lead to false localization results during sampling. The aim of this study was to explore a potential connection between normal anatomical variation in the angioarchitecture of the IPSs and the ACTH results obtained in subsequent IPSS tests. METHODS A retrospective review was performed on all cases between 1998 and 2013 involving patients at a single institution who underwent IPSS for radiographically equivocal pituitary microadenomas. Cases were reviewed for tumor laterality noted on either operative or pathology reports, as well as the presence of angiographic evidence of cross-filling between the sinuses. In addition, ACTH levels from the right and left IPSs were documented at baseline and at 2, 5, and 10 minutes after corticotropin-releasing hormone (CRH) administration. A ratio of the change in ACTH levels measured at the time of maximal response (10 minutes) versus the levels measured at the initial response (2 minutes) was computed for each patient and compared between patients by their angiographic cross-filling status. RESULTS There were 41 patients with a histopathologically confirmed right- or left-sided ACTH-secreting pituitary microadenoma who underwent preoperative IPSS. Among these patients, 28 (68%) showed angiographic evidence of cross-filling between the IPSs, and 13 showed no cross-filling. On average, ACTH levels increased by a factor of 3.91 ± 0.77 in the contralateral IPS in patients with angiographic cross-filling, compared with a factor increase of only 1.80 ± 0.27 in patients without cross-filling (p = 0.014). In comparison, ACTH levels increased by a factor of 2.01 ± 0.57 in the ipsilateral IPS in patients with cross-filling, and by 8.78 ± 7.30 in those without cross-filling (p = 0.373). CONCLUSIONS The presence of angiographic cross-filling, suggestive of a greater degree of vascular channel networking between the right and left IPS, is a significant factor influencing the measured rates of change of ACTH in IPSS and may impact the specificity of this test to accurately determine microadenoma laterality in the preoperative setting.