Garni Barkhoudarian

BACKGROUND AND OBJECTIVES: Craniopharyngiomas (CPs) recur in 20% to 50% of cases after initial management. To date, there are no large multi-institutional series investigating outcomes in patients receiving surgery for recurrent CP. Here, we leverage the Registry of Adenomas of the Pituitary and Related Disorders to analyze outcomes after surgical treatment of recurrent CP. METHODS: Demographic, clinical, radiographic, surgical, and outcome variables were analyzed for 483 patients receiving surgery for primary or recurrent CP across 16 US-based academic skull-base centers comprising the Registry of Adenomas of the Pituitary and Related Disorders consortium from 2000 to 2024. RESULTS: Among the 483 patients, 360 (74.5%) had primary CP and 123 (25.5%) had recurrent CP. The recurrent cohort was younger at initial diagnosis ( P _adj < .01) and recurrence ( P _adj = .02). Adamantinomatous CPs were more common in the recurrent cohort but not significantly so, and 33.3% of cases had prior radiation therapy. Recurrent cases had more frequent preoperative endocrine dysfunction and hormone replacement ( P _adj < .01). Patients with recurrent CP had less frequent suprasellar tumor extension ( P _adj = .04) and more frequent preinfundibular/transinfundibular over retroinfundibular localization ( P _adj = .02). There were no differences in operative approach; endoscopic endonasal surgery was the most common, and procedures achieved similar distributions of gross and subtotal resection in both cohorts ( P _adj = .30) with similar low frequencies of unplanned reoperation and surgical complications. New postoperative arginine vasopressin deficiency (in patients without preoperative arginine vasopressin deficiency) was more common in the primary cohort ( P _adj = .04), but long-term follow-up demonstrated similar frequencies of endocrine dysfunction in both cohorts and comparably low rates (P _adj = .17). CONCLUSION: This study provides the largest comparative evaluation of patients undergoing surgery for recurrent vs primary CP. Despite prior treatment, patients with recurrent CP achieved comparable resection outcomes with similar rates of neuroendocrine dysfunction. These findings indicate surgical resection remains a safe and efficacious option for recurrent CP, especially as emerging targeted therapies become available.

Purpose Clinical screening systems (CSSs) for Cushing syndrome (CS) validated in Europe have not been evaluated for CS or Cushing disease (CD) in the United States (US). We aimed to evaluate existing CSSs in US patients and develop two new symptom-based CSSs to identify patients with high pre-test probability of disease warranting referral for definitive biochemical workup—one for broad CS screening and one specifically for CD. Methods Data were obtained from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID)—comprising 615 patients who underwent transnasal transsphenoidal resection for CD at one of 11 US pituitary centers, the Centers for Disease Control and Prevention’s 2019 National Health Interview Survey (NHIS)—comprising 31,997 US respondents, and a single institution CD-NFA cohort—comprising 468 US patients diagnosed with either CD (n = 385) or nonfunctioning adenoma (n = 83). The RAPID Community Cushing CSS was derived from differences between the RAPID and NHIS cohorts, and the RAPID CD CSS from differences between patients with CD versus NFA. Results In external validation using US-based cohorts, the RAPID Community CSS achieved an AUC of 0.707, compared to the Spanish (AUC = 0.691) and Italian (AUC = 0.685) models, and the RAPID CD CSS demonstrated greater external sensitivity (0.836, threshold = 0.5) at the Youden-optimized threshold than the Spanish (0.605, threshold = 4) and Italian (0.735, threshold = 6) CSSs. Conclusions In US patient populations, the RAPID Community Cushing CSS demonstrated superior discriminative ability for CD compared to the Italian and Spanish CSSs, and the RAPID CD CSS achieved the highest sensitivity for CD among all CSSs evaluated.

BACKGROUND AND OBJECTIVES: In endoscopic endonasal surgery, the Doppler probe has proven useful for localizing the paraclival and cavernous internal carotid arteries (ICA) and avoiding ICA injury. Similarly, during transcranial brain tumor removal, the Doppler probe may help avoid major vascular injury, particularly for tumors encasing or adherent to Circle of Willis branches. In this study, we describe the technique, outcomes, and potential neurovascular benefits of real-time navigation using the Doppler probe during craniotomy for brain tumor removal. METHODS: Patients from 2015 to 2022 who underwent craniotomy for brain tumor resection and the Doppler probe was used were retrospectively analyzed. Data collection included demographics, tumor pathology, incidence of major/minor vascular injury, MRI-confirmed stroke/infarction, and extent of tumor resection. RESULTS: In total, 695 patients underwent 840 craniotomies for brain tumor resection; in 501 craniotomies (59.6%), the Doppler was used. One major vascular injury (0.2%) of a supraclinoid ICA was directly attributed to non-Doppler probe use immediately before vessel injury, leading to stroke and severe neurological decline. There were 7 strokes (1.4%) leading to permanent neurological deficit attributable to vasospasm or small vessel injury and 26 asymptomatic infarctions/strokes (5.2%) attributable to unrecognized vascular injury or spasm at the time of surgery. CONCLUSION: In this series of 501 craniotomies for brain tumor removal where the Doppler probe was used, the rate of direct large vessel injury was under 1%. Although our data show that smaller vessel injuries can still occur and may lead to permanent neurological deficits, routine Doppler probe use may help guide tumor dissection and aggressiveness of removal, avoiding inadvertent major arterial injury. Our experience suggests that it is most useful as tumor dissection progresses as the resulting brain shift makes stereotactic neuronavigation less reliable. We recommend routine Doppler probe use during transcranial brain tumor removal, particularly for tumors encasing or adherent to major arteries.

Two main approaches for microvascular decompression (MVD) for hemifacial spasm (HFS) include the retrosigmoid approach (RA) and the modified trans-jugular-tubercular approach (MTA). This anatomical study compares both and evaluates the value of neuroendoscopy. Dissections were performed on 4 cadaveric human heads, performing RA on one side and MTA on the other. Anatomical landmarks were determined beforehand, and the accessibility to each was evaluated by determining visibility with a microscope, 0°, 30°, and 45° endoscopes. The degree of freedom at each landmark, representing the working area afforded by each approach, was measured using vectors from the boundaries of the craniotomy to the points of interest. MTA yielded 90.1% greater degree of freedom(p<0.00001) at the IAC and 118.3% greater access(p<0.001) to the facial nerve root exit zone than RA. For landmarks with sub-100% microscopic visualization, the 0° endoscope improved visualization for 15/16(94%) landmarks with RA and 9/9(100%) with MTA. Introducing 30° and 45° angled endoscopes improved visualization in every instance. Although MTA provided a higher visualization for some landmarks with the microscope and 0° endoscope, all discrepancies were eliminated with the 30° endoscope, while the 45° endoscope showed identical visualization. Despite the greater degree of freedom with MTA, visualizing and manipulating the facial nerve at the root exit zone was comparable between both approaches, with use of angled endoscopy further improving visualization and accessibility. As such, the endoscope-assisted RA, with its smaller exposure and soft tissue disruption, is a viable approach for MVD for HFS.

BACKGROUND AND OBJECTIVES: The nasoseptal flap (NSF) has been a versatile reconstructive option for extended endonasal skull base surgery, significantly decreasing postoperative cerebrospinal fluid (CSF) leakage rates. One failure mechanism of concern is NSF necrosis. It has been postulated that immediate postoperative MRI flap enhancement can predict flap necrosis. This retrospective study analyzes NSF enhancement to assess for flap viability and CSF leakage. METHODS: Patients from 2012 to 2020 who underwent extended endoscopic endonasal surgery with NSF reconstruction were assessed. Immediate postoperative MRI and delayed 3-month MRI were compared for NSF enhancement. Enhancement was graded as no enhancement, partial, or complete enhancement. Patient demographics, tumor type, intraoperative CSF leak grade, and postoperative CSF leakage were assessed based on flap enhancement patterns. RESULTS: Of 713 patients who underwent endoscopic endonasal surgery, 64 required NSF reconstruction. On the immediate postoperative MRI, 45 patients (70%) had complete flap enhancement, 9 (14%) had partial, and 10 (16%) no enhancement. On the 3-month MRI, 59 patients (92%) had complete flap enhancement and 5 (8%) had partial enhancement. There was significant improvement of flap enhancement between immediate postoperative and 3-month MRI (P = .002). All patients with no initial enhancement had complete enhancement at 3 months. Of those with partial enhancement, 2 remained partial and 7 had complete enhancement at 3 months. Overall, 44 patients (69%) had no change between MRI scans, 17 (27%) improved, and 3 (5%) had decreased enhancement. There was no correlation between intraoperative CSF leak rates and flap enhancement. Four patients had postoperative CSF leaks, 2 having complete immediate enhancement, 1 partial, and 1 without enhancement (P = .85). CONCLUSION: Overall, immediate postoperative MRI NSF enhancement (or lack thereof) did not predict enhancement at the 3-month MRI and did not correlate with postoperative CSF leakage. Hence, one should not rely solely on postoperative flap enhancement to assess the viability of the dural reconstruction.

BACKGROUND AND OBJECTIVES: In endoscopic endonasal approaches (EEAs) for skull base pathologies, endoscope view obscuration remains a persistent, time-consuming, and distracting issue for surgeons and may result in increased operative time. The endonasal access guide (EAG) has been demonstrated as a possible adjunct to minimize these events. However, to date, there have been no comparative studies performed and the potential time savings by using EAGs have yet to be quantified. This cohort study aimed to determine the operative efficiency benefits of the EAG in EEA operations. METHODS: Analysis of EEA operative videos from an EAG cohort (n = 20) and a control cohort (n = 20) was performed, assessing 12-minute segments in the first, middle, and last third of each operation. The first segment in each cohort was selected before EAG placement, serving as an internal control. Every endoscope lens soiling instance was counted (measured as cleaning actions per minute), timed (obscuration time %), and identified as a withdrawal, irrigation, or other cleaning action. Perioperative variables including skull base repair and postoperative cerebrospinal fluid leakage were assessed. RESULTS: Within the EAG cohort, obscuration time was reduced in the middle and last third compared with the first third (3.73% [CI: 2.39-5.07] vs 12.97% [CI: 10.24-15.70], P < .001; 4.19% [CI: 2.83-5.55] vs 12.97% [CI: 10.24-15.70], P < .001) and cleaning actions were also significantly reduced by EAG (0.69/min [CI: 0.39-0.99] vs 1.67/min [CI: 1.34-2.00], P = .001; 0.66/min [CI: 0.35-0.97] vs 1.67/min [CI: 1.34-2.00], P < .001). Between the control and EAG cohorts, there was no significant difference between obscuration time and cleaning actions in the first third (9.33% vs 12.97%, P = .086; 1.34/min vs 1.67/min, P = .151) or in the middle third (6.24% vs 3.73%, P = .140; 0.80/min vs 0.69/min, P = .335), but there was a significant difference in the last third (9.25% [CI: 6.95-11.55] vs 4.19% [CI: 2.83-5.55], P < .001; 0.95/min [CI: 0.73-1.17] vs 0.66/min [CI: 0.35-0.97], P = .018). CONCLUSION: EAG significantly reduces lens obscurations and cleaning events, particularly during the intradural portion of operations. This technology may offer a greater time-saving impact with patients undergoing long EEA operations.

BACKGROUND AND OBJECTIVES: Postoperative cerebrospinal fluid (CSF) leaks and meningitis are well-known risks of retromastoid craniotomy. Use of abdominal fat grafts, collagen allografts, and rigid or semirigid buttresses have demonstrated efficacy in preventing CSF leaks and meningitis in endoscopic endonasal surgery. This study aims to determine the utility of a similar multilayered reconstruction technique for retromastoid craniotomy. METHODS: We retrospectively reviewed 212 consecutive patients who underwent retromastoid craniotomy for tumor removal or microvascular decompression from 2007 to 2022. Scalp incisions were linear or slightly curved, muscle and facia opening was performed sharply avoiding monopolar cautery; craniotomies had a maximum dimension of 3 cm. A primary water-tight dural closure was rarely achieved favoring collagen sponge overlay often augmented with autologous fat. Clinical factors including pathology, mastoid air cell entry, and reconstruction material were analyzed. Outcomes including postoperative CSF leakage and meningitis were assessed. RESULTS: Of 212 patients (mean age 56 ± 16 years; 60% female; 10% with prior surgery), 148 (70%) had tumor resection and 64 (30%) had microvascular decompression. Mastoid air cells were breached in 67%. Collagen sponge dural overlay was used in 201/212 (95%). A fat graft was placed in 116 (55%) cases: 69% with air cell entry, 27% without air cell entry; 158 (75%) patients had their bone flap replaced, 46 (21%) had titanium mesh cranioplasty, 8 (4%) had no bone flap or titanium mesh. There were no CSF leaks or meningitis. One patient had a lumbar drain placement preoperatively, none postoperatively. Median length of stay was 2 days. CONCLUSION: Retromastoid craniotomy multilayered reconstruction with liberal use of collagen sponge and abdominal fat grafts seems to reliably avoid postoperative CSF leaks and meningitis including in the setting of nonwatertight dural closure and mastoid cell entry. Use of shorter incisions, avoidance of monopolar cautery, and a relatively small craniotomy may contribute to the absence of CSF leaks in this series.

Table S2. Individual listing of additional chordoma tissue samples collected for miR WTA.