Predictors of Progression in a Series of 81 Adult Patients Surgically Managed for an Intracranial Hemangioblastoma: Implications for the Postoperative Follow-Up.

The aim was to identify predictors of progression in a series of patients managed for an intracranial hemangioblastoma, in order to guide the postoperative follow-up modalities. The characteristics of 81 patients managed for an intracranial hemangioblastoma between January 2000 and October 2022 were retrospectively analyzed. The mean age at diagnosis was of 48 ± 16 years. Eleven (14%) patients had von Hippel-Lindau disease. The most frequent tumor location was the cerebellar hemispheres (n = 51, 65%) and 11 (14%) patients had multicentric hemangioblastomas. A gross total resection was achieved in 75 (93%) patients. Eighteen (22%) patients had a local progression, with a median progression-free survival of 56 months 95% CI [1;240]. Eleven (14%) patients had a distant progression (new hemangioblastoma and/or growth of an already known hemangioblastoma). Local progression was more frequent in younger patients (39 ± 14 years vs. 51 ± 16 years; p = 0.005), and those with von Hippel-Lindau disease (n = 8, 44% vs. n = 3, 5%, p < 0.0001), multiple cerebral locations (n = 3, 17% vs. n = 2, 3%, p = 0.02), and partial tumoral resection (n = 4, 18% vs. n = 1, 2%, p = 0.0006). Therefore, it is advisable to propose a postoperative follow-up for at least 10 years, and longer if at least one predictor of progression is present.

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

OBJECTIVE: Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS: This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS: There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS: SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.

Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients. METHODS: This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded. RESULTS: The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%-14.3%) at 5 years and 23.6% (95% CI 0%-42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic. CONCLUSIONS: Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.

Repeat stereotactic radiosurgery for persistent cerebral arteriovenous malformations in pediatric patients.

OBJECTIVE: The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients. METHODS: Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation. RESULTS: The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%-7.8%) at 1 year to 44% (95% CI 32%-55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%-62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%-16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed. CONCLUSIONS: The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.

Facial Nerve Schwannoma Treatment with Stereotactic Radiosurgery (SRS) versus Resection followed by SRS: Outcomes and a Management Protocol.

Background Stereotactic radiosurgery (SRS) and resection are treatment options for patients with facial nerve schwannomas without mass effect. Objective This article evaluates outcomes of patients treated with SRS versus resection + SRS. Method We retrospectively compared 43 patients treated with SRS to 12 patients treated with resection + SRS. The primary study outcome was unfavorable combined endpoint, defined as worsening or new clinical symptoms, and/or tumor radiological progression. SRS (38.81 ± 5.3) and resection + SRS (67.14 ± 11.8) groups had similar clinical follow-ups. Results At the time of SRS, the tumor volumes of SRS (mean ± standard error; 1.83 ± 0.35 mL) and resection + SRS (2.51 ± 0.75 mL) groups were similar. SRS (12.15 ± 0.08 Gy) and resection + SRS (12.16 ± 0.14 Gy) groups received similar radiation doses. SRS group (42/43, 98%) had better local tumor control than the resection + SRS group (10/12, 83%, p = 0.04). Most of SRS (32/43, 74%) and resection + SRS (10/12, 83%) group patients reached a favorable combined endpoint following SRS ( p = 0.52). Considering surgical associated side effects, only 2/10 patients of the resection + SRS group reached a favorable endpoint ( p < 0.001). Patients of SRS group, who are > 34 years old ( p = 0.02), have larger tumors (> 4 mL, 0.04), internal auditory canal (IAC) segment tumor involvement ( p = 0.01) were more likely to reach an unfavorable endpoint. Resection + SRS group patients did not show such a difference. Conclusion While resection is still needed for larger tumors, SRS offers better clinical and radiological outcomes compared to resection followed by SRS for facial schwannomas. Younger age, smaller tumors, and non-IAC situated tumors are factors that portend a favorable outcome.

A Novel Approach for Free, Affordable, and Sustainable Microsurgery Laboratory Training for Low- and Middle-Income Countries: University of Wisconsin-Madison Microneurosurgery Laboratory Experience.

BACKGROUND AND OBJECTIVES: In low- and middle-income countries (LMICs), approximately 5 million essential neurosurgical operations per year remain unaddressed. When compared with high-income countries, one of the reasons for this disparity is the lack of microsurgery training laboratories and neurosurgeons trained in microsurgical techniques. In 2020, we founded the Madison Microneurosurgery Initiative to provide no-cost, accessible, and sustainable microsurgery training opportunities to health care professionals from LMICs in their respective countries. METHODS: We initially focused on enhancing our expertise in microsurgery laboratory training requirements. Subsequently, we procured a wide range of stereo microscopes, light sources, and surgical instrument sets, aiming to develop affordable, high-quality, and long-lasting microsurgery training kits. We then donated those kits to neurosurgeons across LMICs. After successfully delivering the kits to designated locations in LMICs, we have planned to initiate microsurgery laboratory training in these centers by providing a combination of live-streamed, offline, and in-person training assistance in their institutions. RESULTS: We established basic microsurgery laboratory training centers in 28 institutions across 18 LMICs. This was made possible through donations of 57 microsurgery training kits, including 57 stereo microscopes, 2 surgical microscopes, and several advanced surgical instrument sets. Thereafter, we organized 10 live-streamed microanastomosis training sessions in 4 countries: Lebanon, Paraguay, Türkiye, and Bangladesh. Along with distributing the recordings from our live-streamed training sessions with these centers, we also granted them access to our microsurgery training resource library. We thus equipped these institutions with the necessary resources to enable continued learning and hands-on training. Moreover, we organized 7 in-person no-cost hands-on microanastomosis courses in different institutions across Türkiye, Georgia, Azerbaijan, and Paraguay. A total of 113 surgical specialists successfully completed these courses. CONCLUSION: Our novel approach of providing microsurgery training kits in combination with live-streamed, offline, and in-person training assistance enables sustainable microsurgery laboratory training in LMICs.

Stereotactic radiosurgery for nonfunctioning pituitary tumor: A multicenter study of new pituitary hormone deficiency.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS: Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS: A total of 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR): 18.9]) were treated using a median margin dose of 14Gy (IQR: 4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio [HR]:0.33, 95% CI: 0.18-0.60, P < 0.001). The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI: 11-19.4) at 5 and 10 years, respectively. A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR: 3.47, 95% CI: 1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph, and growth hormone deficiency was 8% (95% CI: 3.9-11.9), 8.3% (95% CI: 3.9-12.5), 3.5% (95% CI: 1.7-5.2), and 4.7% (95% CI: 1.9-7.4), respectively at 10 years. CONCLUSIONS: SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.

Use of 5-ALA fluorescence-guided surgery versus white-light conventional microsurgery for the resection of newly diagnosed glioblastomas (RESECT study): a French multicenter randomized phase III study.

OBJECTIVE: Only one phase III prospective randomized study, published in 2006, has assessed the performance of 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) for glioblastoma resection. The aim of the RESECT study was to compare the onco-functional results associated with 5-ALA fluorescence and with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care. METHODS: This was a phase III prospective randomized single-blinded study, involving 21 French neurosurgical centers, comparing 5-ALA FGS with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care, including neuronavigation use and postoperative radiochemotherapy. Randomization was performed in a 1:1 ratio stratified by institution. 5-ALA (20 mg/kg) or placebo (ascorbic acid) was administered orally 3-5 hours before the incision. The primary endpoint was the rate of gross-total resection (GTR) blindly assessed by an independent committee. Patients without a confirmed pathological diagnosis of glioblastoma or with unavailable postoperative MRI studies were excluded from the per-protocol analysis. RESULTS: Between March 2013 and August 2016, a total of 171 patients were assigned to the 5-ALA fluorescence group (n = 88) or to the placebo group (n = 83). Twenty-four cases were excluded because the WHO histological criteria of grade 4 glioma were not met. The proportion of GTR was significantly higher in the 5-ALA fluorescence group (53/67, 79.1%) than in the placebo group (33/69, 47.8%; p = 0.0002). After adjustment for age, preoperative Karnofsky Performance Scale score, and tumor location, GTR was still associated with 5-ALA fluorescence (OR 4.13 [95% CI 1.94-8.79]). The mean 7-day postoperative Karnofsky Performance Scale score (≥ 80% in 49/71, 69.0% [5-ALA group]; 50/71, 70.4% [placebo group], p = 0.86) and the proportion of patients with a worsened neurological status 3 months postoperatively (9/68, 13.2% [5-ALA group]; 9/70, 12.9% [placebo group], p = 0.95) were similar between groups. Adverse events related to 5-ALA intake were rare and consisted of photosensitization in 4/87 (4.6%) patients and hepatic cytolysis in 1/87 (1.1%) patients. The 6-month PFS (70.2% [95% CI 57.7%-79.6%] and 68.4% [95% CI 55.7%-78.1%]; p = 0.39) and 24-month OS (30.1% [95% CI 18.9%-42.0%] and 37.7% [95% CI 25.8%-49.5%]; p = 0.89) did not significantly differ. In multivariate analysis, GTR was an independent predictor of PFS (hazard ratio 0.56 [95% CI 0.36-0.86], p = 0.008) and OS (hazard ratio 0.65 [95% CI 0.42-1.01], p = 0.05). The use of 5-ALA FGS generates a significant extra cost of 2732.36€ (95% CI 1658.40€-3794.11€). CONCLUSIONS: The authors found that 5-ALA FGS is an easy-to-use, cost-effective, and minimally time-consuming technique that safely optimizes the extent of resection in patients harboring glioblastoma amenable to a large resection.

Interrater reliability in neurology objective structured clinical examination across specialties.

PURPOSE: To assess interrater reliability and examiners' characteristics, especially specialty, associated with scoring of neurology objective structured clinical examination (OSCE). MATERIAL AND METHODS: During a neurology mock OSCE, five randomly chosen students volunteers were filmed while performing 1 of the 5 stations. Video recordings were scored by physicians from the Lyon and Clermont-Ferrand university teaching hospitals to assess students performance using both a checklist scoring and a global rating scale. Interrater reliability between examiners were assessed using intraclass coefficient correlation. Multivariable linear regression models including video recording as random effect dependent variable were performed to detect factors associated with scoring. RESULTS: Thirty examiners including 15 (50%) neurologists participated. The intraclass correlation coefficient of checklist scores and global ratings between examiners were 0.71 (CI95% [0.45-0.95]) and 0.54 (CI95% [0.28-0.91]), respectively. In multivariable analyses, no factor was associated with checklist scores, while male gender of examiner was associated with lower global rating (ß coefficient = -0.37; CI 95% [-0.62-0.11]). CONCLUSIONS: Our study demonstrated through a video-based scoring method that agreement among examiners was good using checklist scoring while moderate using global rating scale in neurology OSCE. Examiner's specialty did not affect scoring whereas gender was associated with global rating scale.

Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biological effective dose (BED) has shown promising results in 2 previous studies as a predictive variable for outcomes in adults, but its role has never been studied in pediatric outcomes. METHODS: Retrospective data for patients 18 years or younger treated with a single-session SRS for AVMs were collected from 1989 to 2019. BED calculations were performed using an α/ß ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using 2 models (margin dose vs BED). RESULTS: One hundred ninety-seven patients (median age = 13.1 years, IQR = 5.2) were included; 72.6% (143/197) of them presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQR = 4.0) with a median BED of 183.2 Gy (IQR = 70.54) was used to treat AVM with a median volume of 2.8 cm 3 (IQR = 2.9). After SRS, obliteration was confirmed in 115/197 patients (58.4%) using magnetic resonance imaging and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+ = 2.2-67.4), and 66.0% (95% CI = 56.0-73.7) at 3, 5, and 10 years, respectively. In Cox multivariate analysis, a BED >180 Gy (hazard ratio [HR] = 2.11, 95% CI = 1.30-3.40, P = .002) in model 1 and a margin dose >20 Gy (HR = 1.90, 95% CI = 1.15-3.13, P = .019) in model 2 were associated with obliteration. An AVM nidus volume >4 cm 3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose was associated with RIC occurrence, with the only predictive factor being deep AVM location (HR = 3, 95% CI = 1-9.1, P = .048). CONCLUSION: This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

Clinical outcomes following stereotactic radiosurgery for cerebral cavernous malformations of the basal ganglia and thalamus.

OBJECTIVE: There are few reports of outcomes following stereotactic radiosurgery (SRS) for the management of cerebral cavernous malformations (CCMs) of the basal ganglia or thalamus. Therefore, the authors aimed to clarify these outcomes. METHODS: Centers participating in the International Radiosurgery Research Foundation were queried for CCM cases managed with SRS from October 2001 to February 2021. The primary outcome of interest was hemorrhage-free survival (HFS) with a secondary outcome of symptomatic adverse radiation events (AREs). Assessment of the association of prognostic factors with HFS was conducted via Kaplan-Meier analysis and log-rank test. Chi-square tests were conducted to assess potential factors associated with the incidence of AREs. RESULTS: Seventy-three patients were identified. The median patient age was 43.5 years (range 4.4-79.5 years). Fifty-nine (80.8%) patients had hemorrhage prior to SRS. The median treatment volume was 0.9 cm3 (range 0.07-10.1 cm3) with a median margin prescription dose (MPD) of 12 Gy (range 10-20 Gy). One-, 3-, 5-, and 10-year HFS were 93.0%, 89.9%, 89.9%, and 83.0%, respectively, with one hemorrhage-related death approximately 1 year after SRS and nearly 60% and 30% of patients having improvement or stability of symptoms, respectively. There was no correlation between lesion size or MPD and HFS. Seven (9.6%) patients experienced AREs (MPDs > 12 Gy in all cases). Lesion size > 1.0 cm3 was correlated with the incidence of an ARE (p = 0.019). Forty-two (93.3%) of 45 patients treated with an MPD ≤ 12 Gy experienced neither hemorrhage nor AREs following SRS versus 17 (60.7%) of 28 patients treated with an MPD > 12 Gy (p = 0.0006). CONCLUSIONS: SRS is a reasonable treatment strategy and confers clinical stability or improvement and hemorrhage avoidance in patients harboring CCMs of the basal ganglia or thalamus. An MPD of approximately 12 Gy is recommended for the management of CCM.

Third Stereotactic Radiosurgery for Residual Arteriovenous Malformations: A Retrospective Multicenter Study.

BACKGROUND AND OBJECTIVES: There are no studies evaluating the efficacy and safety of more than 2 stereotactic radiosurgery (SRS) procedures for cerebral arteriovenous malformations (AVM). The aim of this study was to provide evidence on the role of third single-session SRS for AVM residual. METHODS: This multicenter, retrospective study included patients managed with a third single-session SRS procedure for an AVM residual. The primary study outcome was defined as AVM nidus obliteration without AVM bleeding or symptomatic radiation-induced changes (RIC). Secondary outcomes evaluated were AVM obliteration, AVM hemorrhage, asymptomatic, and symptomatic RIC. RESULTS: Thirty-eight patients (20/38 [52.6%] females, median age at third SRS 34.5 [IQR 20] years) were included. The median clinical follow-up was 46 (IQR 14.8) months, and 17/38 (44.7%) patients achieved favorable outcome. The 3-year and 5-year cumulative probability rates of favorable outcome were 23% (95% CI = 10%-38%) and 53% (95% CI = 29%-73%), respectively. The cumulative probability of AVM obliteration at 3 and 5 years after the third SRS was 23% (95% CI = 10%-37%) and 54% (95% CI = 29%-74%), respectively. AVM bleeding occurred in 2 patients, and 1 of them underwent subsequent resection. The cumulative probability rate of post-SRS AVM hemorrhage remained constant at 5.3% (95% CI = 1%-16%) during the first 5 years of follow-up. Transient symptomatic RIC managed conservatively occurred in 5/38 patients (13.2%) at a median time of 12.5 (IQR 22.5) months from third SRS. Radiation-induced cyst formation was noted in 1 patient (4.2%) 19 months post-SRS. No mortality, radiation-associated malignancy, or permanent symptomatic RIC was noted during follow-up. CONCLUSION: A third single-session SRS to treat a residual intracranial AVM offers obliteration in most patients. The risk of RIC was low, and these effects were transient. While not often required, a third SRS can be performed in patients with persistent residual AVMs.

Effect of cerebral arteriovenous malformation location on outcomes of repeat, single-fraction stereotactic radiosurgery: a matched-cohort analysis.

OBJECTIVE: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. METHODS: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. RESULTS: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). CONCLUSIONS: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

Stereotactic radiosurgery for haemorrhagic cerebral cavernous malformation: a multi-institutional, retrospective study.

BACKGROUND: Cerebral cavernous malformations (CCMs) frequently manifest with haemorrhages. Stereotactic radiosurgery (SRS) has been employed for CCM not suitable for resection. Its effect on reducing haemorrhage risk is still controversial. The aim of this study was to expand on the safety and efficacy of SRS for haemorrhagic CCM. METHODS: This retrospective multicentric study included CCM with at least one haemorrhage treated with single-session SRS. The annual haemorrhagic rate (AHR) was calculated before and after SRS. Recurrent event analysis and Cox regression were used to evaluate factors associated with haemorrhage. Adverse radiation effects (AREs) and occurrence of new neurological deficits were recorded. RESULTS: The study included 381 patients (median age: 37.5 years (Q1-Q3: 25.8-51.9) with 414 CCMs. The AHR from diagnosis to SRS excluding the first haemorrhage was 11.08 per 100 CCM-years and was reduced to 2.7 per 100 CCM-years after treatment. In recurrent event analysis, SRS, HR 0.27 (95% CI 0.17 to 0.44), p<0.0001 was associated with a decreased risk of haemorrhage, and the presence of developmental venous anomaly (DVA) with an increased risk, HR 1.60 (95% CI 1.07 to 2.40), p=0.022. The cumulative risk of first haemorrhage after SRS was 9.4% (95% CI 6% to 12.6%) at 5 years and 15.6% (95% CI% 9 to 21.8%) at 10 years. Margin doses> 13 Gy, HR 2.27 (95% CI 1.20 to 4.32), p=0.012 and the presence of DVA, HR 2.08 (95% CI 1.00 to 4.31), p=0.049 were factors associated with higher probability of post-SRS haemorrhage. Post-SRS haemorrhage was symptomatic in 22 out of 381 (5.8%) patients, presenting with transient (15/381) or permanent (7/381) neurological deficit. ARE occurred in 11.1% (46/414) CCM and was responsible for transient neurological deficit in 3.9% (15/381) of the patients and permanent deficit in 1.1% (4/381) of the patients. Margin doses >13 Gy and CCM volume >0.7 cc were associated with increased risk of ARE. CONCLUSION: Single-session SRS for haemorrhagic CCM is associated with a decrease in haemorrhage rate. Margin doses ≤13 Gy seem advisable.

Incorporation of Brain Connectomics for Stereotactic Radiosurgery Treatment Planning.

BACKGROUND AND IMPORTANCE: Neurosurgeons have integrated neuroanatomy-based tractography to avoid critical structures during dose planning. However, they have yet to integrate more comprehensive connectome networks for radiosurgical planning. CLINICAL PRESENTATION: A young man presented with a Spetzler-Martin Grade 3 right temporal arteriovenous malformation. DISCUSSION: As proof of concept, we incorporated connectomic networks including default mode network, optic radiation and central executive network into the Gamma Knife radiosurgical treatment planning workflow. Connectome networks were created from T1 anatomic and diffusion-weighted images magnetic resonance images using Quicktome software. The resulting networks were voxel-encoded in the magnetic resonance images, imported into GammaPlan, and segmented by image thresholding. The GammaPlan Lightning optimizer was used to create radiosurgical plans with a dose of 20 Gy to the 50% isodose line delivered to the arteriovenous malformation nidus both with and without treating these networks as risk structures. When taking into account the connectome networks, a maximum dose restriction of 14 Gy was placed on each network during lightning dose planning. With default mode network, optic radiation, and central executive network as risk structures, the maximum dose and V 12Gy were reduced by 23.4% and 88.3%, 20% and 34.3%, and 29.8% and 63.2%, respectively. CONCLUSION: We were able to incorporate connectomes into radiosurgical dose planning approaches. This allowed for dose reductions to the networks while still achieving delivery of a therapeutic dose to the target volume.

Epilepsy associated with cerebral cavernous malformations managed with stereotactic radiosurgery: an international, multicenter study.

OBJECTIVE: Stereotactic radiosurgery (SRS) has been proposed as an alternative to resection for epilepsy control in patients with cerebral cavernous malformations (CCM) located in critical areas. METHODS: This multicentric, retrospective study evaluated seizure control in patients with a solitary CCM and a history of at least one seizure prior to SRS. RESULTS: 109 patients (median age at diagnosis 28.9 years, interquartile range (IQR) 16.4 years] were included. Prior to SRS, 2 (1.8%) were seizure-free without medication, 35 (32.1%) were seizure-free with antiseizure medications (ASM), 17 (15.6%) experienced an improvement of at least 50% in seizure frequency/intensity with ASM, and 55 (50.5%) experienced an improvement of less than 50% in seizure frequency/intensity with ASM. At a median follow-up of 3.5 years post-SRS (IQR: 4.9), 52 (47.7%) patients were Engel class I, 13 (11.9%) class II, 17 (15.6%) class III, 22 (20.2%) class IVA or IVB and 5 (4.6%) class IVC. For the 72 patients who had seizures despite medication prior to SRS, a delay > 1.5 years between epilepsy presentation and SRS decreased the probability to become seizure-free, HR 0.25 (95% CI 0.09-0.66), p = 0.006. The probability of achieving Engel I at the last follow-up was 23.6 (95% CI 12.7-33.1) and 31.3% (95% CI 19.3-50.8) at 2 and 5 years respectively. 27 patients were considered as having drug-resistant epilepsy. At a median follow-up of 3.1 years (IQR: 4.7), 6 (22.2%) of them were Engel I, 3 (11.1%) Engel II, 7 (25.9%) Engel III, 8 (29.6%) Engel IVA or IVB and 3 (11.1%) Engel IVC. INTERPRETATION: 47.7% of patients managed with SRS for solitary CCM presenting with seizures achieved Engel class I at the last follow-up.

Volumetric Assessment of Nonfunctional Pituitary Adenoma Treated With Stereotactic Radiosurgery: An Assessment of Long-Term Response.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is widely used to manage recurrent or residual nonfunctioning pituitary adenomas (NFPAs). Studies on the long-term volumetric response of NFPAs to SRS are lacking. Such a post-SRS volumetric study will allow us to set up appropriate radiographic follow-up protocols and predict tumor volumetric response. METHODS: Two providers independently performed volumetric analyses on 54 patients who underwent single-session SRS for a recurrent/residual NFPA. In the case of discrepancy between their results, the final volume was confirmed by an independent third provider. Volumetry was performed on the 1-, 3-, 5-, 7-, and 10-year follow-up neuroimaging studies. RESULTS: Most patients showed a favorable volumetric response, with 87% (47/54) showing tumor regression and 13% (7/54) showing tumor stability at 10 years. Year 3 post-SRS volumetric results correlated (R 2 = 0.82, 0.63, 0.56) with 5-, 7-, and 10-year outcomes. The mean interval volumetric reduction was 17% on year 1; further interval volumetric reduction was 17%, 9%, 4%, and 9% on years 3, 5, 7, and 10, respectively. CONCLUSION: Year 3 post-SRS volumetric response of patients with residual or recurrent NFPAs is predictive of their 7-10-year follow-up response. For patients demonstrating NFPA regression in the first 1-3 years, interval follow-up MRI's can likely be performed at 2-year periods unless otherwise clinically indicated. Further studies are needed to better define the volumetric response to adenomas more than a decade after SRS.

Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations.

BACKGROUND: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation. METHODS: This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. Follow-up began at repeat SRS. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. RESULTS: The cohort comprised 505 patients (254 [50.3%] males; median [interquartile range] age, 34 [15] years) from 14 centers. The median clinical and magnetic resonance imaging follow-up was 52 (interquartile range, 61) and 47 (interquartile range, 52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability, 50% [95% CI, 45%-55%]) and obliteration by 300 (59.4%) patients (5-year probability, 56% [95% CI, 51%-61%]). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4 cm3, subdistribution hazard, 0.61 [95% CI, 0.44-0.86]; P=0.005; >4 cm3, subdistribution hazard, 0.47 [95% CI, 0.32-0.7]; P<0.001) and brainstem/basal ganglia involvement (subdistribution hazard, 0.6 [95% CI, 0.45-0.81]; P<0.001) were associated with reduced probability of favorable outcome. CONCLUSIONS: Repeat SRS confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first 3 years, extending the latency period to 5 years generally increases the rate of favorable patient outcomes and reduces the necessity of a third intervention.

A novel injectable radiopaque hydrogel with potent properties for multicolor CT imaging in the context of brain and cartilage regenerative therapy.

Cell therapy is promising to treat many conditions, including neurological and osteoarticular diseases. Encapsulation of cells within hydrogels facilitates cell delivery and can improve therapeutic effects. However, much work remains to be done to align treatment strategies with specific diseases. The development of imaging tools that enable monitoring cells and hydrogel independently is key to achieving this goal. Our objective herein is to longitudinally study an iodine-labeled hydrogel, incorporating gold-labeled stem cells, by bicolor CT imaging after in vivo injection in rodent brains or knees. To this aim, an injectable self-healing hyaluronic acid (HA) hydrogel with long-persistent radiopacity was formed by the covalent grafting of a clinical contrast agent on HA. The labeling conditions were tuned to achieve sufficient X-ray signal and to maintain the mechanical and self-healing properties as well as injectability of the original HA scaffold. The efficient delivery of both cells and hydrogel at the targeted sites was demonstrated by synchrotron K-edge subtraction-CT. The iodine labeling enabled to monitor the hydrogel biodistribution in vivo up to 3 days post-administration, which represents a technological first in the field of molecular CT imaging agents. This tool may foster the translation of combined cell-hydrogel therapies into the clinics.

Stereotactic Radiosurgery for Intracranial Meningiomas.

Meningiomas are thought to originate from the meningothelial cells of the arachnoid mater and are the most common primary brain tumor in adults. Histologically confirmed meningiomas occur with an incidence of 9.12/100,000 population and account for 39% of all primary brain tumors and 54.5% of all non-malignant brain tumors. Risk factors for meningioma include age 65 years and older, female gender, African-American race, history of exposure to head and neck ionizing radiation, and certain genetic disorders such as neurofibromatosis II. Intracranial meningiomas are the most commonly benign, WHO Grade I neoplasms. Atypical and anaplastic are considered malignant lesions.