Impulsivity Markers in Parkinsonian Subthalamic Single-Unit Activity.

BACKGROUND: Impulsive-compulsive behaviors are common in Parkinson's disease (PD) patients. However, the basal ganglia dysfunctions associated with high impulsivity have not been fully characterized. The objective of this study was to identify the features associated with impulsive-compulsive behaviors in single neurons of the subthalamic nucleus (STN). METHODS: We compared temporal and spectral features of 412 subthalamic neurons from 12 PD patients with impulsive-compulsive behaviors and 330 neurons from 12 PD patients without. Single-unit activities were extracted from exploratory microrecordings performed during deep brain stimulation (DBS) implant surgery in an OFF medication state. RESULTS: Patients with impulsive-compulsive behaviors displayed decreased firing frequency during bursts and a larger fraction of tonic neurons combined with weaker beta coherence. Information carried by these features led to the identification of patients with impulsive-compulsive behaviors with an accuracy greater than 80%. CONCLUSIONS: Impulsive-compulsive behaviors in PD patients are associated with decreased bursts in STN neurons in the OFF medication state. © 2021 International Parkinson and Movement Disorder Society.

Atypical and malignant meningioma: outcome and prognostic factors in 68 irradiated patients.

Meningiomas account for up to 20 % of all primary intracranial neoplasms; although the majority of these have a benign course, as many as 5-10 % can display more aggressive behavior and a higher incidence of disease progression. The benefit of immediate adjuvant radiotherapy is still being debated for atypical and malignant meningiomas. This study aimed to retrospectively assess prognostic factors and outcome in 68 patients with atypical and malignant meningiomas. Sixty-eight meningioma patients were treated with radiotherapy after initial resection or for recurrence, between January 1993 and December 2011. Surgery was macroscopically complete in 80 % of the patients; histology was atypical and malignant in 51 patients and 17 patients, respectively. Mean dose of radiotherapy was 54.6 Gy. Fifty-six percent of all patients received radiotherapy after surgical resection, 26 % at the first relapse, and 18 % at the second relapse. Median follow-up was 6.7 years, (range 1.5-19.9 years). The 5- and 10-year actuarial overall survival (OS) rates were 74.1 and 45.6 %, respectively. At univariate analysis age >60 years, radiotherapy dose >52 Gy showed statistical significance, (p = 0.04 and p = 0.03, respectively). At the multivariate analysis radiotherapy dose >52 Gy maintained the statistical significance, (p = 0.037). OS of patients treated with radiotherapy at diagnosis was longer than the survival of patients treated with salvage radiotherapy; however this difference did not reach statistical significance when tested for the entire series or for the subgroups of grade 2 and grade 3 patients. The 5- and 10-year disease-free survival (DFS) rates were 76.5 and 69.5 %, respectively, and were significantly influenced by size >5 cm (p = 0.04) and grading (p = 0.003) on univariate analysis. At multivariate analysis, size and grading both remained significant prognostic factors, p = 0.044 and p = 0.0006, respectively. Grade ≤ 2 acute side effects were seen during radiotherapy treatment in 16 % of the patients, with no ≥ grade 3 acute toxicity, based on the Common Terminology Criteria for Adverse Events. In this mono-institutional retrospective study, age and radiotherapy dose were associated with a longer OS, while preoperative size and grading of the tumor influenced DFS. Although there were some advantages in terms of OS for patients treated with postoperative radiotherapy, the benefit did not reach the significance. Multicenter prospective studies are necessary to clarify the management and the correct timing of radiotherapy in such a rare disease.

Impulsivity is associated with firing regularity in parkinsonian ventral subthalamic nucleus.

Impulsive-compulsive behaviors (ICB) are over-represented in Parkinson's disease (PD) patients. Neurons in the ventral subthalamic nucleus (STN) might play a predominant role in the modulation of impulsivity. We characterized the firing regularity of 742 subthalamic neurons from 24 PD patients (12 ICB+ and 12 ICB-) in an OFF medication state. We computed the firing regularity in the dorsal and ventral STN regions, and we compared their performance in discriminating ICB patients. Regularity of ventral neurons in ICB+ patients is higher and supports a significant discrimination between the two cohorts. These results substantiate a ventral location of neurons involved in impulsivity.

Surgical Resolution of Trigeminal Neuralgia Complicating Vestibular Schwannoma Removal.

This work illustrates the case of surgical treatment of trigeminal neuralgia (TN), as a tardive complication after vestibular schwannoma (VS) removal (Koos III, Figure 1), in a female patient. After VS surgery, the postoperative computed tomography scan did not show any significant complication, although a thin blood clot was present in the surgical bed (Figure 2). However, 3 months later, our patient developed a TN involving the territories V2-V3. Medical therapies were ineffective. Several magnetic resonance imaging scans confirmed a left dislocation of the brainstem (Figures 3 and 4), probably due to the previous clot retraction. The anatomic-functional preservation of the left Tn was documented using the laser-evoked potentials. Fifteen months after surgery, our patient underwent a second operation aimed at exploring the Tn territory, with the use of the intraoperative monitoring and mapping the fifth and seventh cranial nerves. A neurovascular conflict, caused by scar tissue involving the superior cerebellar artery, a small vein, and the Tn, was detected and surgically solved (Figure 5). Postoperative analgesic treatment was progressively reduced and suspended. The case is illustrated and explained in the Video 1. The paucity of cases reported in the literature lead us to think that TN as complication of VS removal is underestimated because it may be responsive to medical treatment. Laser-evoked potentials may be useful to study the integrity of the Tn, ensuring that no anatomic damage has been done during surgery. On the basis of our experience, surgery can be an effective treatment option when TN is not responsive to medical therapy and the anatomic-functional integrity of the Tn has been preserved.

Clinical outcomes and secondary glaucoma after gamma-knife radiosurgery and Ruthenium-106 brachytherapy for uveal melanoma: a single institution experience.

We retrospectively analyzed data from records of 48 patients (48 eyes) treated with gamma-knife (n = 18) or Ruthenium-106 brachytherapy (n = 30) for uveal melanoma, in our Ocular Oncology Unit between December 2013 and September 2019, with the aim to evaluate treatment outcomes, and incidence and risk factors for secondary glaucoma. Patients demographics and tumor characteristics at diagnosis were recorded. Follow-up data were collected regarding local tumor control, treatment complications, enucleation need, metastases occurrence and survival status. The median follow-up period was 33.7 months in the gamma-knife group and 26.2 months in the brachytherapy group. The mean tumor thickness, the largest basal diameter and the tumor volume were significantly higher in the gamma-knife group than in the brachytherapy group. The local tumor control rate was 100% in the brachytherapy group and 77.8% in the gamma-knife group. In the gamma-knife group, six patients were enucleated, no patient treated with brachytherapy underwent enucleation. The overall survival rate was 96.7% in the brachytherapy group and 94.44% in the gamma-knife group. Secondary glaucoma occurred in 10 patients after gamma-knife and in one patient after brachytherapy: it should be emphasized that larger lesions were treated with gamma-knife, whereas smaller tumors were selected for brachytherapy. We found a significative correlation of tumor thickness (P value = 0.043) and volume (P value = 0.040) with secondary glaucoma occurrence after gamma-knife treatment. Moreover, secondary glaucoma significantly correlated with radiation retinopathy in the gamma-knife group (P value = 0.009). This study shows preliminary clinical results that could be useful for further studies with more patients and longer follow-up.

Immunotherapy in association with stereotactic radiotherapy for non-small cell lung cancer brain metastases: results from a multicentric retrospective study on behalf of AIRO.

BACKGROUND: To define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology). METHODS: NSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT. RESULTS: One hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate. CONCLUSIONS: Combined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT.

Outcome and prognostic factors for older patients undergoing radiosurgery for brain metastases.

PURPOSE: Older patients with brain metastases (BM) are often excluded from clinical trials. The aim of our study was to investigate the outcomes following Gamma Knife radiosurgery (GKRS) in young old (65-74 years) and very old (≥75 years) patients with BM. METHODS: Between October 2012 and October 2018, we treated 89 patients aged ≥65 years with GKRS. Patients were divided in two group: young old (YO) and very old (VO) patients. At baseline G8, Graded Prognostic Assessment (DS-GPA) and Basic Score for Brain Metastases (BSBM) were assessed for all patients. Survival analysis was estimated using the Kaplan-Meier (KM) method. Cox regression model was used to investigate the influence of significant factors on KM. RESULTS: Median age at the time of GKRS was 72.2 years (range 65-87). A mean of 2.52 lesions were treated per patient (range 1-14). Median overall survival (OS) for YO and VO patients was 14.2 and 15.7 months, respectively. At univariate analysis, there were no significant differences in OS between the two age groups. A high BSBM (p ≤ .0001) and a high DS-GPA score (p = .0069) were associated with longer survival. A low DS-GPA score was the most powerful independent factor for predicting short survival (HR 1.76, 95% CI 1.25-2.46, p = .001) at multivariate analysis. CONCLUSION: GKRS is a safe approach to treat BM in elderly patients. DS-GPA score represents an important prognostic factor for survival in elderly patients undergoing GKRS.

Multimodal Management of Metastatic Malignant Meningiomas: The Role of Radiosurgery in Long-Term Local Control.

BACKGROUND: Metastatic meningiomas (MMs) are rare (0.1 of 100 cases). Their treatment requires a multimodal approach, with surgery, radiotherapy, chemotherapy, and radiosurgery, which allows a long-term local control (LC) and an extension of free survival. In this study, the authors performed a review of the literature and reported 2 cases of patients affected by extracranial MMs, with long-term follow-up. CASE DESCRIPTION: Case 1: A 48-year-old woman was admitted for resection of an extra-axial falx lesion (meningioma G1). After 2 years, the lesion got a local recurrence, resected with a histologic diagnosis of meningioma G3. During the next 9 years, the patient underwent 5 Gamma Knife radiosurgery (GKRS) procedures for local recurrence. At 56 years, she was readmitted for a surgical local recurrence (histologic definition: anaplastic meningioma G3). At the age of 62, the patient underwent a right lobectomy for a lung mass (histologic diagnosis: anaplastic meningioma G3). After that, multiple lesions at soma L5 and adrenal gland were discovered and then monitored. Case 2: A 48-year-old woman was operated for a lesion involving torcular herophili (meningioma G2). After 3 years, a local recurrence requires GKRS combined with tamoxifen. In the next 7 years, she underwent 5 GKRS procedures for local recurrence. The patient also underwent chemotherapy with octreotide. At the age of 61, she discovered multiple lesions in both lungs, liver, and kidney. A hepatic biopsy showed anaplastic meningioma G3. Also this patient does not suffer from any neurologic or clinical deficits. CONCLUSIONS: LC in malignant meningioma is achievable through a multimodal approach; GKRS makes possible LC, but a novel aspect of these lesions is opened to discussion: the metastases. These reports show that multimodal treatment for MMs is an effective approach with good LC and improvement of overall survival. However, a long survival may allow systemic diffusion of the disease, in particular, when sagittal sinus is involved.

Management and Surgical Approaches of Brainstem Cavernous Malformations: Our Experience and Literature Review.

INTRODUCTION: Brainstem cavernous malformations (BSCMs) are clusters of dilated sinusoidal channels. Clinical presentation is characterized by focal neurological deficits and/or hemorrhage. The goal of this study is to analyze surgical indications and approaches in a series of patients with BSCM and review pertinent literature and suggest prognostic factors related to the anatomical, clinical, and surgical data collected. METHODS: We retrospectively reviewed the clinical data of 55 patients with BSCM, treated at three centers, from January 2006 to March 2016. We collected anagraphic data, pre and postoperative neurological status, pre and postradiological images, surgical procedures, and follow-up results. We summarized the anatomical, clinical, and surgical aspects of the lesions and identified two large groups based on the chosen approach: lateral and medial. Clinical and radiological results were then compared. RESULTS: The series comprised 55 patients. Hemorrhagic onset was observed in all patients. Suboccipital, retrosigmoid, anterior, subtentorial, subtemporal, transvermian, telovelar, far lateral and trans, and infratentorial approaches were performed. Neurological status improved postoperatively in 34 cases at last follow-up. Five patients showed clinical neurological worsening. Total resection was achieved in 46 cases and, during a mean follow-up of 63.4 months, no recurrence or re-bleeding occurred in those patients. The mean follow-up was 63.9 months. The mean modified Rankin Scale at final follow-up was used to analyze the results and draw our conclusions. CONCLUSIONS: A reasonable surgical approach, selection, and gentle handling of the surrounding structures are required to prevent impairment of neurologic function and avoid partial resection.

Preoperative Magnetic Resonance and Intraoperative Computed Tomography Fusion for Real-Time Neuronavigation in Intramedullary Lesion Surgery.

BACKGROUND: Image-guided surgery techniques in spinal surgery are usually based upon fluoroscopy or computed tomography (CT) scan, which allow for a real-time navigation of bony structures, though not of neural structures and soft tissue remains. OBJECTIVE: To verify the effectiveness and efficacy of a novel technique of imaging merging between preoperative magnetic resonance imaging (MRI) and intraoperative CT scan during removal of intramedullary lesions. METHODS: Ten consecutive patients were treated for intramedullary lesions using a navigation system aid. Preoperative contrast-enhanced MRI was merged in the navigation software, with an intraoperative CT acquisition, performed using the O-arm TM system (Medtronic Sofamor Danek, Minneapolis, Minnesota). Dosimetric and timing data were also acquired for each patient. RESULTS: The fusion process was achieved in all cases and was uneventful. The merged imaging information was useful in all cases for defining the exact area of laminectomy, dural opening, and the eventual extension of cordotomy, without requiring exposition corrections. The radiation dose for the patients was 0.78 mSv. Using the authors' protocol, it was possible to merge a preoperative MRI with navigation based on intraoperative CT scanning in all cases. Information gained with this technique was useful during the different surgical steps. However, there were some drawbacks, such as the merging process, which still remains partially manual. CONCLUSION: In this initial experience, MRI and CT merging and its feasibility were tested, and we appreciated its safety, precision, and ease.