Object: Optimal case management after surgical removal of brain metastasis remains controversial. Although postoperative whole-brain radiation therapy (WBRT) has been shown to prevent local recurrence and decrease deaths, this modality can substantially decrease neurocognitive function and quality of life. Stereotactic radiosurgery (SRS) can theoretically achieve the same level of local control with fewer side effects, although studies conclusively demonstrating such outcomes are lacking. To assess the effectiveness and safety profile of tumor bed SRS after resection of brain metastasis, the authors performed a retrospective analysis of 110 patients who had received such treatment at the Centre Hospitalier Universitaire de Sherbrooke. They designed the study to identify risk factors for local recurrence and placed special emphasis on factors that could potentially be addressed.Methods: Patients who had received treatment from 2004 through 2013 were included if they had undergone surgical removal of 1 or more brain metastases and if the tumor bed was treated by SRS regardless of the extent of resection or prior WBRT. All cases were retrospectively analyzed for patient and tumor-specific factors, treatment protocol, adverse outcomes, cavity outcomes, and survival for as long as follow-up was available. Univariate and multivariate Cox regression analyses were performed to identify risk factors for local recurrence and predictors of increased survival times.Results: Median patient age at first SRS treatment was 58 years (range 37–84 years). The most frequently diagnosed primary tumor was non–small cell lung cancer. The rate of gross-total resection was 81%. The median Karnofsky Performance Scale score was 90%. Tumor bed SRS was performed at a median of 3 weeks after surgery. Median follow-up and survival times were 10 and 11 months, respectively. Actuarial local control of the cavity at 12 months was 73%; median time to recurrence was 6 months. According to multivariate analysis, risk factors for recurrence were a longer surgery-to-SRS delay (HR 1.625, p = 0.003) and a lower maximum radiation dose delivered to the cavity (HR 0.817, p = 0.006). Factors not associated with increased recurrence were subtotal or piecemeal resections, prior WBRT, histology of the primary tumor, and larger cavity volume. No factors predictive of survival were identified. Symptomatic radiation-induced enhancement occurred in 6% of patients and leptomeningeal dissemination in 11%. Pathologically confirmed radiation-induced necrosis occurred in 1 (0.9%) patient.Conclusions: Adjuvant tumor bed SRS after the resection of brain metastasis is a valuable alternative to adjuvant WBRT. Risk factors for local recurrence are lower maximum radiation dose and a surgery-to-SRS delay longer than 3 weeks. Outcomes were not worse for patients who had undergone prior WBRT and subtotal or piecemeal resections. Pending the results of prospective randomized controlled trials, the authors' study supports the safety and efficacy of adjuvant SRS after resection of brain metastasis. SRS should be performed as early as possible, ideally within 3 weeks of the surgery.
Tremor is a prevalent symptom associated with multiple conditions, including essential tremor (ET), Parkinson’s disease (PD), multiple sclerosis (MS), stroke and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (ventral intermediate nucleus of the thalamus (Vim), prelemniscal radiations (Raprl), caudal zona incerta (Zi), thalamus (Vo) and subthalamic nucleus (STN)) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.
Chronic subdural hematoma (CSDH) is one of the most frequent reason for cranial neurosurgical consultation. There is no widely accepted medical treatment for this condition. Herein, we present the protocol for the Tranexamic Acid (TXA) in Chronic Subdural Hematomas (TRACS) trial aiming at determining whether TXA can increase the rate of CSDH resolution following conservative management, lower the number of required surgical procedures and decrease the rate of CSDH recurrence following surgical evacuation. TRACS is a multicenter, double-blind, randomized, parallel-design, placebo-controlled, phase IIB study designed to provide preliminary efficacy data as well as feasibility, safety and incidence data required to plan a larger definitive phase III trial. Consecutive patients presenting with a diagnosis of chronic subdural hematoma will be screened for eligibility. Exclusion criteria include: specific risk factors for thromboembolic disease, anticoagulant use or contraindication to TXA. A total of 130 patients will be randomized to receive either 750 mg of TXA daily or placebo until complete radiological resolution of the CSDH or for a maximum of 20 weeks. CSDH volume will be measured on serial computed tomography (CT) scanning. Cognitive function tests, quality of life questionnaires as well as functional autonomy assessments will be performed at enrollment, at 10 weeks following randomization and at 3 months following treatment cessation. During the treatment period, patients will undergo standard CSDH management with surgery being performed at the discretion of the treating physician. If surgery is performed, the CSDH and its outer membrane will be sampled for in vitro analysis. The primary outcome is the rate of CSDH resolution by 20 weeks without intervening unplanned surgical procedure. Secondary outcomes include: CSDH volume, incidence of surgical evacuation procedures, CSDH recurrence, cognitive functions, functional autonomy, quality of life, incidence of complications and length of hospital stay. Planned subgroup analyses will be performed for conservatively versus surgically managed subjects and highly versus poorly vascularized CSDH. CSDH is a frequent morbidity for which an effective medical treatment has yet to be discovered. The TRACS trial will be the first prospective study of TXA for CSDH. NCT ID: NCT02568124 .
9 February 2021 in Journal of Neurology, Neurosurgery & Psychiatry
Background Focused ultrasound (FUS) was approved as a new treatment modality for essential tremor (ET) in 2016. The goal of this study was to quantify FUS adoption for ET and understand its drivers. Methods The adoption of the various surgical options for ET was estimated using three measures: the number of presentations on the various surgical treatments for ET at specialised international meetings, the number of original papers published as identified by literature searches and the number of thalamotomy procedures performed worldwide for ET as provided by device manufacturers’ registries. Results First, we found that the number of presentations related to lesioning procedures is increasing relative to deep brain stimulation (DBS) at international meetings. Second, there are already more publications on FUS (93) than stereotactic radiosurgery (SRS) (68) or radiofrequency (43) for ET, although they still lag behind DBS papers (750). Third, the number of annual FUS thalamotomies performed for ET (n>1200 in 2019) in 44 centres has surpassed the annual procedures across 342 Gamma Knife units (n<400, 2018) but is yet to reach the number of DBS cases for ET estimated at over 2400/year. Conclusion FUS is being rapidly adopted for the treatment of ET. We hypothesise that its perceived minimally invasive nature coupled with the ability to perform intraoperative clinical assessments, its immediate effects and active marketing efforts are contributing factors. As lesioning modalities for the treatment of ET are reappraised, the superior popularity of FUS over SRS appears to arise for reasons other than differences in clinical outcomes.
Chronic subdural hematoma (cSDH) is a frequent yet poorly studied entity. Patients with cSDH are increasingly using antithrombotic medication, are now older, and present with a variety of clinical symptoms, including incidental discoveries. Despite this increasing complexity, management has remained roughly unchanged since the late 1990s. We review here the state of cSDH research under way at Université de Sherbrooke and around the world with a focus on studies addressing specific gaps in the current evidence base. We show that evidence is lacking at many decision points in the typical cSDH patient treatment algorithm. No definition of cSDH is universally accepted, and a formal definition project, along with suggested common data elements to be reported in future trials (CODE-CSDH: formal cSDH definition project) is ongoing. An amendment to International Statistical Classification of Diseases and Related Health Problems(ICD-11) has also been proposed to improve classification and registry research. Within the cSDH clinical assessment, evidence for the occurrence of nonepileptic, stereotypical, and intermittent symptoms (NESIS) is emerging. The GENESIS study (Generation Evidence on the etiology and management of NESIS) will test etiological and therapeutic hypotheses for this patient subpopulation. For patients at high risk of recurrence, the TRACS (TXA for cSDH) and EMMACS studies (Embolization of the Middle Meningeal Artery in Chronic Subdural Hematoma study) are, respectively, assessing the use of tranexamic acid and meningeal artery embolization. The overarching vision is that patients with cSDH might be stratified for operative versus conservative treatment based on the need for mass effect removal, then be offered adjuvant therapies based on their risk of recurrence and thrombotic complications. We believe that such tailoring of therapy to each individual should help improve outcomes.