Impact of combined use of intraoperative MRI and awake microsurgical resection on patients with gliomas: a systematic review and meta-analysis.

Microsurgical resection of primary brain tumors located within or near eloquent areas is challenging. Primary aim is to preserve neurological function, while maximizing the extent of resection (EOR), to optimize long-term neurooncological outcomes and quality of life. Here, we review the combined integration of awake craniotomy and intraoperative MRI (IoMRI) for primary brain tumors, due to their multiple challenges. A systematic review of the literature was performed, in accordance with the Prisma guidelines. Were included 13 series and a total number of 527 patients, who underwent 541 surgeries. We paid particular attention to operative time, rate of intraoperative seizures, rate of initial complete resection at the time of first IoMRI, the final complete gross total resection (GTR, complete radiological resection rates), and the immediate and definitive postoperative neurological complications. The mean duration of surgery was 6.3 h (median 7.05, range 3.8-7.9). The intraoperative seizure rate was 3.7% (range 1.4-6; I^2 = 0%, P heterogeneity = 0.569, standard error = 0.012, p = 0.002). The intraoperative complete resection rate at the time of first IoMRI was 35.2% (range 25.7-44.7; I^2 = 66.73%, P heterogeneity = 0.004, standard error = 0.048, p < 0.001). The rate of patients who underwent supplementary resection after one or several IoMRI was 46% (range 39.8-52.2; I^2 = 8.49%, P heterogeneity = 0.364, standard error = 0.032, p < 0.001). The GTR rate at discharge was 56.3% (range 47.5-65.1; I^2 = 60.19%, P heterogeneity = 0.01, standard error = 0.045, p < 0.001). The rate of immediate postoperative complications was 27.4% (range 15.2-39.6; I^2 = 92.62%, P heterogeneity < 0.001, standard error = 0.062, p < 0.001). The rate of permanent postoperative complications was 4.1% (range 1.3-6.9; I^2 = 38.52%, P heterogeneity = 0.123, standard error = 0.014, p = 0.004). Combined use of awake craniotomy and IoMRI can help in maximizing brain tumor resection in selected patients. The technical obstacles to doing so are not severe and can be managed by experienced neurosurgery and anesthesiology teams. The benefits of bringing these technologies to bear on patients with brain tumors in or near language areas are obvious. The lack of equipoise on this topic by experienced practitioners will make it difficult to do a prospective, randomized, clinical trial. In the opinion of the authors, such a trial would be unnecessary and would deprive some patients of the benefits of the best available methods for their tumor resections

Differential contributions of subthalamic beta rhythms and 1/f broadband activity to motor symptoms in Parkinson's disease.

Excessive beta oscillatory activity in the subthalamic nucleus (STN) is linked to Parkinson's Disease (PD) motor symptoms. However, previous works have been inconsistent regarding the functional role of beta activity in untreated Parkinsonian states, questioning such role. We hypothesized that this inconsistency is due to the influence of electrophysiological broadband activity -a neurophysiological indicator of synaptic excitation/inhibition ratio- that could confound measurements of beta activity in STN recordings. Here we propose a data-driven, automatic and individualized mathematical model that disentangles beta activity and 1/f broadband activity in the STN power spectrum, and investigate the link between these individual components and motor symptoms in thirteen Parkinsonian patients. We show, using both modeled and actual data, how beta oscillatory activity significantly correlates with motor symptoms (bradykinesia and rigidity) only when broadband activity is not considered in the biomarker estimations, providing solid evidence that oscillatory beta activity does correlate with motor symptoms in untreated PD states as well as the significant impact of broadband activity. These findings emphasize the importance of data-driven models and the identification of better biomarkers for characterizing symptom severity and closed-loop applications

Benefits of combined use of 68−Ga Dotatoc and 5-ALA fluorescence for recurrent atypical skull-base meningioma after previous microsurgery and Gamma Knife radiosurgery: a case report.

Studies of novel microsurgical adjuncts, such as 5-aminolevulinic acid (5-ALA) fluorescence have shown various fluorescence patterns within meningiomas, opening new avenues for complete microsurgical resection. Here, we present a recurrent, radiation-induced meningioma, previously operated on two occasions (initial gross total resection and subtotal 12 years later) and also irradiated by Gamma Knife radiosurgery (GKR, 6 years after the first surgery). We thought to assess the usefulness of <sup>68-</sup> Ga Dotatoc in surgical target planning and of 5-ALA as an adjunct for maximal microsurgical excision. We report on a 43 years-old Caucasian male diagnosed with atypical, radiation induced WHO II meningioma, with left basal temporal bone implantation. Hodgkin lymphoma treated with cranial and mediastinal radiation during infancy marked his personal history. He underwent a first gross total microsurgical resection, followed 6 and 12 years later by Gamma Knife radiosurgery (GKR) and second subtotal microsurgical resection, respectively. Magnetic resonance imaging (MRI) displayed new recurrence 13 years after initial diagnosis. He was clinically asymptomatic but routine Magnetic resonance imaging showed constant progression. There was strong <sup>68-</sup> Ga Dotatoc uptake. We used 5-ALA guided microsurgical resection. Intraoperative views confirmed strong fluorescence, in concordance with both preoperative Magnetic resonance imaging enhancement and <sup>68-</sup> Ga Dotatoc. The tumor was completely removed, with meningeal and bone resection. The authors conclude that fluorescence-guided resection using 5-ALA is useful for recurrent atypical, radiation-induced meningioma even despite previous irradiation and multiple recurrences

Gamma Knife radiosurgery as salvage therapy for gangliogliomas after initial microsurgical resection.

Gangliogliomas (GG) are considered WHO grade I rare tumors. While they commonly manifest as temporal lobe epilepsy, they can be located anywhere in the brain. Primary treatment is complete microsurgical resection. Remnant or recurrent GG can benefit from radiation therapy. Here, we present a series of GG who received Gamma Knife radiosurgery (GKR) after initial microsurgery. Between October 2009 and February 2020, four patients benefitted from such approach. The median age at surgery was 16 years (mean 17, 11-25) and at the time of GKR was 22.5 years (mean 23, 19-28). Initial clinical symptom was epilepsy in 3 cases and incidental in one. Biopsy was firstly performed in one case. One patient had stereotactic electroencephalography. The respective anatomical locations were right parieto-occipital, sylvian, left paraventricular and left inferior parietal. Gamma Knife radiosurgery was performed after a median time of 3.5 years after initial gross total microsurgical resection (GTR). The median follow-up after GKR was 54 months (mean 58.5, 6-120). The median marginal dose was 18 Gy (mean 17.5, 16-18). The median target volume was 0.5 mL (mean 0.904, 0.228-2.3). The median prescription isodose volume was 0.6 mL (mean 0.9, 0.3-2.4). At last follow-up, GG majorly decreased in 3 patients, remained stable in one. Gamma Knife radiosurgery is safe and effective for remnant GG after GTR. Primary treatment remains microsurgical resection, especially in cases with symptomatic mass effect or with epilepsy. Single fraction GKR can be a valuable option for remnant or recurrent tumors after initial resection

How to combine the use of intraoperative magnetic resonance imaging (MRI) and awake craniotomy for microsurgical resection of hemorrhagic cavernous malformation in eloquent area: a case report.

Cavernous malformations are clusters of abnormal and hyalinized capillaries without interfering brain tissue. Here, we present a cavernous malformation operated under awake conditions, due to location, in an eloquent area and using intraoperative magnetic resonance imaging due to patient's movement upon the awake phase. We present the pre-, per-, and postoperative course of an inferior parietal cavernous malformation, located in eloquent area, in a 27-year-old right-handed Caucasian male, presenting with intralesional hemorrhage and epilepsy. Preoperative diffusion tensor imaging has shown the cavernous malformation at the interface between the arcuate fasciculus and the inferior fronto-occipital fasciculus. We describe the microsurgical approach, combining preoperative diffusion tensor imaging, neuronavigation, awake microsurgical resection, and intraoperative magnetic resonance imaging. Complete microsurgical en bloc resection has been performed and is feasible even in eloquent locations. Intraoperative magnetic resonance imaging was considered an important adjunct, particularly used in this case as the patient moved during the "awake" phase of the surgery and thus neuronavigation was not accurate anymore. Postoperative course was marked by a unique, generalized seizure without any adverse event. Immediate and 3 months postoperative magnetic resonance imaging confirmed the absence of any residue. Pre- and postoperative neuropsychological exams were unremarkable

Tumor control and trigeminal dysfunction improvement after stereotactic radiosurgery for trigeminal schwannomas: a systematic review and meta-analysis.

Trigeminal nerve schwannomas (TS) are uncommon intracranial tumors, frequently presenting with debilitating trigeminal and/or oculomotor nerve dysfunction. While surgical resection has been described, its morbidity and mortality rates are non-negligible. Stereotactic radiosurgery (SRS) has emerged with variable results as a valuable alternative. Here, we aimed at reviewing the medical literature on TS treated with SRS so as to investigate rates of tumor control and symptomatic improvement. We reviewed manuscripts published between January 1990 and December 2019 on PubMed. Tumor control and symptomatic improvement rates were evaluated with separate meta-analyses. This meta-analysis included 18 studies comprising a total of 564 patients. Among them, only one reported the outcomes of linear accelerators (Linac), while the others of GK. Tumor control rates after SRS were 92.3% (range 90.1-94.5; p < 0.001), and tumor decrease rates were 62.7% (range 54.3-71, p < 0.001). Tumor progression rates were 9.4% (range 6.8-11.9, p < 0.001). Clinical improvement rates of trigeminal neuralgia were 63.5% (52.9-74.1, p < 0.001) and of oculomotor nerves were 48.2% (range 36-60.5, p < 0.001). Clinical worsening rate was 10.7% (range 7.6-13.8, p < 0.001). Stereotactic radiosurgery for TS is associated with high tumor control rates and favorable clinical outcomes, especially for trigeminal neuralgia and oculomotor nerves. However, patients should be correctly advised about the risk of tumor progression and potential clinical worsening. Future clinical studies should focus on standard reporting of clinical outcomes

Biologically effective dose and prediction of obliteration of unruptured arteriovenous malformations treated by upfront Gamma Knife radiosurgery: a series of 149 consecutive cases.

Arteriovenous malformations (AVMs) present no pathologic tissue, and radiation dose is confined in a clear targeted volume. The authors retrospectively evaluated the role of the biologically effective dose (BED) after Gamma Knife radiosurgery (GKRS) for brain AVMs. A total of 149 consecutive cases of unruptured AVMs treated by upfront GKRS in Lille University Hospital, France, were included. The mean length of follow-up was 52.9 months (median 48, range 12-154 months). The primary outcome was obliteration, and the secondary outcome was complication appearance. The marginal dose was 24 Gy in a vast majority of cases (n = 115, 77.2%; range 18-25 Gy). The mean BED was 220.1 Gy2.47 (median 229.9, range 106.7-246.8 Gy2.47). The mean beam-on time was 32.3 minutes (median 30.8, range 9-138.7 minutes). In the present series, the mean radiation dose rate was 2.259 Gy/min (median 2.176, range 1.313-3.665 Gy/min). The Virginia score was 0 in 29 (19.5%), 1 in 61 (40.9%), 2 in 41 (27.5%), 3 in 18 (12.1%), and 4 in 0 (0%) patients, respectively. The mean Pollock-Flickinger score was 1.11 (median 1.52, range 0.4-2.9). Univariate (for obliteration and complication appearance) and multivariate (for obliteration only) analyses were performed. A total of 104 AVMs (69.8%) were obliterated at the last follow-up. The strongest predictor for obliteration was BED (p = 0.03). A radiosurgical obliteration score is proposed, derived from a fitted multivariable model: (0.018 × BED) + (1.58 × V12) + (-0.013689 × beam-on time) + (0.021 × age) - 4.38. The area under the receiver operating characteristic curve was 0.7438; after internal validation using bootstrap methods, it was 0.7088. No statistically significant relationship between radiation dose rate and obliteration was found (p = 0.29). Twenty-eight (18.8%) patients developed complications after GKRS; 20 (13.4%) of these patients had transient adverse radiological effects (perilesional edema developed). Predictors for complication appearance were higher prescription isodose volume (p = 0.005) and 12-Gy isodose line volume (V12; p = 0.001), higher Pollock-Flickinger (p = 0.02) and Virginia scores (p = 0.003), and lower beam-on time (p = 0.03). The BED was the strongest predictor of obliteration of unruptured AVMs after upfront GKRS. A radiosurgical score comprising the BED is proposed. The V12 appears as a predictor for both efficacy and toxicity. Beam-on time was illustrated as statistically significant for both obliteration and complication appearance. The radiation dose rate did not influence obliteration in the current analysis. The exact BED threshold remains to be established by further studies