Two fractions staged Gammaknife radiosurgery for "large" cerebral metastases.

BACKGROUND: Gammaknife radiosurgery (GKRS) is a valuable option to control cerebral metastases. However, the risk (adverse radiation effect (ARE))-benefit (local control (LC)) ratio switches when the target is too large. OBJECTIVE: In order to balance this ratio, two fractions staged GKRS protocol was conducted for "large" cerebral metastases. The aim of this study is to evaluate the outcome (LC, ARE). METHODS: A total of 39 large cerebral metastases in 35 patients were treated. The initial mean tumor volume was 14.6 cc [6.1; 35.8]. The prescription margin dose was 12 Gy on the 50% isodose line, with 2 weeks between them. A majority of primary cancer were from lung (43%), melanoma (20%) or breast (17%) origin. The mean age was 63 years old (31-89). Mean Graded Prognostic Assessment (GPA) was 2. RESULTS: At the second fraction, mean tumor volume was 10.3 cc [1.9-27.4]. The mean percentage of volume variation for decreasing lesions was 29%. At last follow-up, mean tumor volume was 7.4 cc [0-25.2]; 34 lesions decreased volume (mean 35%). A decreased volume of more than 45% after first stage GKRS was able to predict a long-term local response to staged GKRS treatment. Local control rate at 6 months and 1 year was 87.3% and 75% respectively. The rate of ARE was 7.7%. No predictive factor of local control or ARE was found in a univariate analysis. CONCLUSION: The new 2-fractions-dose-staged GKRS concept seems to be a well-tolerated and effective treatment option for large cerebral metastases.

Long-term follow-up of an overexposure radiation incident in a cohort treated with linear accelerator-based stereotactic radiosurgery for intracranial arteriovenous malformations.

OBJECTIVE: Dosimetric radiosurgery incidents are rare and probably insufficiently reported in scientific publications. After a long follow-up (FU), the authors studied the outcomes of patients treated with overexposure radiation for arteriovenous malformation (AVM) administered via stereotactic radiosurgery (SRS) at their department. METHODS: Between May 2006 and June 2007, 22 patients were treated for AVM with SRS. The mean (range) patient age was 43.5 (11.8-78) years. Previous treatments were embolization (n = 10), SRS (1), and surgery (1). The average (range) volume was 2.1 (0.2-6.4) cm3. The median prescribed minimal dose was 18.0 Gy. An initial error in the estimation of scatter factors led to overexposure to radiation. Due to this incident, the median delivered minimum dose was 25.0 Gy. All patients were prospectively followed with clinical examination and imaging. RESULTS: The mean (range) clinical FU was 14.5 (12.0-15.2) years. AVM obliteration after SRS was completed in 90.9% of patients at a mean (range) of 39.4 (24.4-70.4) months. No patient had post-SRS AVM bleeding. Three patients (13.6%) had new permanent deficits due to radiation-induced changes (RICs). Obliteration without new deficits was achieved in 18 patients (81.8%). Two patients had new epilepsy that was probably due to RIC but well controlled. The median (range) MRI FU was 13.8 (2.5-14.9) years. During MRI FU, two RIC periods were observed: one classic period during the first 3 years showed T1-weighted annular irregular enhancement (13%), and the other period between 5 and 15 years after SRS showed the occurrence of cystic and hemorrhagic lesions (22.7%). There were no cases of radiation-induced tumor. CONCLUSIONS: The present long-term report showed that this overexposure incident probably increased the AVM obliteration rate. This overexposure seems to have induced RIC and in particular a higher rate of cystic and hemorrhagic late lesions with nevertheless moderate clinical consequences. Long-term FU for AVM is mandatory due to the risk of late RIC.

Safety and Effectiveness of First-line Endovascular Management of Low-Grade Brain Arteriovenous Malformations : Single Center Experience in 145 Patients.

PURPOSE: Spetzler-Martin grade (SMG) I-II (low-grade) brain arteriovenous malformations (BAVMs) are often considered safe for microsurgical resection; however, the role of endovascular treatment (EVT) remains to be clarified in this indication, especially for unruptured BAVMs. The purpose of our study was to assess the safety and effectiveness of endovascular treatment as the first-line treatment for low-grade BAVMs. METHODS: From our local database, we retrospectively retrieved patients with low-grade BAVMs, either ruptured or unruptured, treated by embolization as first-line treatment in our department between January 2005 and January 2020. The primary endpoint was the total obliteration rate of BAVMs, and secondary endpoints were hemorrhagic complications and final clinical outcome, assessed through shift of the modified Rankin scale, and mortality rate secondary to BAVM embolization. RESULTS: A total of 145 patients meeting inclusion criteria and treated by EVT as first-line therapy were included in the study (82 ruptured and 63 unruptured BAVMs). Overall, complete exclusion of BAVMs was achieved in 110 patients (75.9%); 58 patients (70.7%) with ruptured and 52 (82.5%) unruptured BAVMs, including 37.9% BAVMs excluded by EVT alone (35.5% among ruptured and 44.4% among unruptured BAVMs) and 38% by combined treatment (EVT and surgery or EVT and SRS). There was no BAVM volume cut-off predictive for total obliteration by embolization alone. Early minor hemorrhagic complications were reported in 14 patients (9.6%) and early major hemorrhagic complications were reported in 5 patients (3.4%). No late hemorrhagic complications (0%) occurred; mortality rate was 0.7% (1/145 patients). Improved/unchanged mRS was reported in 137 patients (94.5%). CONCLUSION: Endovascular treatment alone or associated with others exclusion techniques, might be safe and effective for complete exclusion of low-grade brain arteriovenous malformations regardless of the volume.

Chronic low back pain during COVID-19 lockdown: is there a paradox effect?

PURPOSE: The coronavirus 2019 (COVID-19) pandemic led to a compulsory lockdown of 3 months with strict restrictions. The impact of the COVID-19 pandemic has shown broad repercussions on patients with chronic pain; especially for conditions that present a significant emotional participation such as chronic low back pain (cLBP). METHODS: We performed a prospective study on 50 patients. Pre- and 1-month post-lockdown questionnaires such as: the Impact of Event Scale (IES), the Oswestry Disability Index (ODI), the Roland-Morris questionnaire (RMQ) and the visual analogue scale (VAS) for back and leg pain intensity were collected. RESULTS: The mean time of the evolution of cLBP was 33.04 months (range 5-120 months). Eighteen (36%) patients improved their cLBP (i-cLBP), whereas for 14 (28%) it was worse (w-cLBP). Cox multivariate proportional hazard model identified that MODIC 1 disc disease [OR 19.93, IC95% (2.81-102.13), p = 0.015] and at-home workouts [OR 18.854, IC95% (1.151-204.9), p = 0.040] were good prognosis factors of the improvement of cLBP while subclinical/mild Covid-19 anxiety (IES score < 26) was a poor prognosis factor in improving cLBP [OR 0.21, IC95% (0.001-0.384), p = 0.009]. Furthermore, pre-lockdown benzodiazepine medication [OR 2.554, IC95% (1.20-9.9), p = 0.002] was a prognosis factor of worse cLBP. In contrast, patients with severe Covid-19 anxiety (IES score > 26) significantly improved their cLBP [OR 0.58, IC95% (0.025-0.834), p = 0.01]. CONCLUSION: Lockdown affected the somatic component of cLBP by decreasing activities and physical measures, whereas the SARS-CoV-2 pandemic spectrum paradoxically improved the psychic and emotional component of cLBP.

Upfront and Repeated Gamma-Knife Radiosurgery for Small (≤5 mL) Unruptured Brain Arteriovenous Malformation: A Cohort of 249 Consecutive Patients.

OBJECTIVE: According to A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), conservative treatment seems to be superior to any intervention for unruptured brain arteriovenous malformations (AVMs). This study aims to evaluate safety and efficacy of upfront and repeated Gamma-Knife Radiosurgery (GKRS) in patients harboring small AVMs fulfilling the inclusion criteria of ARUBA. METHODS: A retrospective study was conducted to evaluate outcomes of unruptured naive brain AVM with a volume ⩽ 5 mL eligible to ARUBA treated by GKRS with at least 3 years of follow-up. RESULTS: From 1992 to 2014, 249 patients fulfilled the inclusion criteria of this study. The median age was 36 years (range: 18-78 years). The median treated volume of the nidus was 1.3 mL (range: 0.4-5 mL) and 63% of the AVM were in eloquent areas. Radiosurgery-based AVM score was 1-1.8 (76%), the Spetzler-Martin grade was II-III (73%), and the Virginia Radiosurgery AVM scale was ≤1 point (75%). The overall AVM obliteration rate was 77.1% after up to 3 GKRS sessions. The median dose at the margin was 24 Gy (15-25 Gy) and the median follow-up was 45 months (range: 36-205 months). Eight patients (3.2%) experienced hemorrhage after GKRS, corresponding to a post-GKRS hemorrhage annual rate of 1.03%. Permanent symptomatic radio-induced changes rate was 2% (4 increased seizures, 1 neurologic deficit). CONCLUSIONS: The very low toxicity rate and the high occlusion rate suggest in favor of upfront and repeated GKRS for unruptured small AVMs (⩽5 mL).

Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review.

Stereotactic radiosurgery (SRS) is a standard option for brain metastases (BM). There is lack of consensus when patients have a systemic treatment, if a washout is necessary. The aim of this review is to analyze the toxicity of SRS when it is concurrent with chemotherapies, immunotherapy, and/or targeted therapies. From Medline and Embase databases, we searched for English literature published up to April 2020 according to the PRISMA guidelines, using for key words the list of the main systemic therapies currently in use And "radiosurgery," "SRS," "GKRS," "Gamma Knife," "toxicity," "ARE," "radiation necrosis," "safety," "brain metastases." Studies reporting safety or toxicity with SRS concurrent with systemic treatment for BM were included. Of 852 abstracts recorded, 77 were included. The main cancers were melanoma, lung, breast, and renal carcinoma. These studies cumulate 6384 patients. The median SRS dose prescription was 20 Gy [12-30] .For some, they compared a concurrent arm with a non-concurrent or a SRS-alone arm. There were no skin toxicities, no clearly increased rate of bleeding, or radiation necrosis with significant clinical impact. SRS combined with systemic therapy appears to be safe, allowing the continuation of treatment when brain SRS is considered.

Stereotactic radiosurgery for thalamus arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations or angiomas are congenital vascular anomalies defined by abnormal arteriovenous shunt. MATERIALS AND METHODS: We conducted a retrospective study between January 1992 and December 2010 at the Timone Hospital radiosurgery unit, 1557 patients were treated by radiosurgery for arteriovenous malformation of which 53 for thalamic localization (3,4%). RESULTS: The mean age was 35.8-/+16.6 years (4-75). 14 patients underwent pre-radiosurgical embolization (26.4%), discovery mode for 47 patients (88.7%) was haemorrhage. The average treatment volume was 1.43 cm3. The average RBAS score was 1.36. The average prescription to the 50% isodose envelope delivered was 22.9 +/-2.9 Gy (12-30), the median margin dose was 24 Gy. Our global obliteration rate after one or two procedures 66.7% for an average follow-up period of 56.7 months. We noted 3.9% of mortality, 5.9% of bleeding after procedure and 3.9% of radio-induced neurological deficit. CONCLUSION: Radiosurgery became indispensable in the treatment of thalamic AVM even when there is a persistent risk of haemorrhage until total recovery.

Stereotactic Radiation Therapy for Renal Cell Carcinoma Brain Metastases in the Tyrosine Kinase Inhibitors Era: Outcomes of 120 Patients.

BACKGROUND: The objective of the study was to evaluate the outcomes in terms of efficacy and safety of a large consecutive series of 362 patients with renal cell carcinoma (RCC) brain metastases treated using stereotactic radiosurgery (SRS) in the tyrosine kinase inhibitor (TKI) era. PATIENTS AND METHODS: From 2005 to 2015, 362 consecutive patients with brain metastases from RCC were treated using SRS in 1 fraction: 226 metastases (61 patients) using Gamma-Knife at a median of 18 Gy (50% isodose line); 136 metastases (63 patients) using linear accelerator at a median of 16 Gy (70% isodose line). The median patient age was 58 years. At the first SRS, 37 patients (31%) received a systemic treatment. Among systemic therapies, TKIs were the most common (65%). RESULTS: The local control rates were 94% and 92% at 12 and 36 months, respectively. In multivariate analysis, a minimal dose >17 Gy and concomitant TKI treatment were associated with higher rates of local control. The overall survival rates at 12 and 36 months were 52% and 29%, respectively. In multivariate analysis, factors associated with poor survival included age ≥65 years, lower score index for SRS, concomitant lung metastases, time between RCC diagnosis and first systemic metastasis ≤4 months, occurrence during treatment with a systemic therapy, no history of neurosurgery, and persistence or occurrence of neurological symptoms at 3 months after SRS. Seventeen patients had Grade III/IV adverse effects of whom 3 patients presented a symptomatic radionecrosis. CONCLUSION: SRS is highly effective in patients with brain metastases from RCC. Its association with TKIs does not suggest higher risk of neurologic toxicity.

Gamma Knife radiosurgery for glossopharyngeal neuralgia: A study of 21 patients with long-term follow-up.

Objective Glossopharyngeal neuralgia (GPN) is a very rare condition, affecting the patient's quality of life. We report our experience in drug-resistant, idiopathic GPN, treated with Gamma Knife radiosurgery (GKRS), in terms of safety and efficiency, on a very long-term basis. Methods The study was opened, self-controlled, non-comparative and bicentric (Marseille and Lausanne University Hospitals). Patients treated with GKRS between 2003 and 2015 (models C, 4C and Perfexion) were included. A single 4-mm isocentre was positioned in the cisternal portion of the glossopharyngeal nerve, with a targeting based both on magnetic resonance imaging (MRI) and computed tomography (CT). The mean maximal dose delivered was 81.4 ± 6.7 Gy (median = 85 Gy, range = 60-90 Gy at the 100% isodose line). Results Twenty-one patients (11 women, 10 men) benefited from 25 procedures. The mean follow-up period was 5.2 ± 3 years (range = 0.9-12.1 years). Seventeen (81%) were initially pain-free after GKRS. At three months, six months and one year after radiosurgery, the percentage of patients with good outcome (BNI classes I to IIIA) was 87.6%, 100% and 81.8%, respectively. Ten cases (58.8%) from the initial pain-free ones had a recurrence, after a mean period of 13.6 ± 10.4 months (range = 3.1-36.6 months). Only three patients (14.2%) had recurrences (two for each one of them) requiring further surgeries. Three patients underwent a second GKRS procedure; one case needed a third GKRS. The former procedures were performed at 7, 17, 19 and 30 months after the first one, respectively. Furthermore, two patients needed additional interventions. At last follow-up, 17 cases (80.9%) were still pain-free without medication. The actuarial pain relief without new surgery was 83%. A transient complication (paraesthesia of the edge of the tongue) was seen in one case (4.8%). Conclusion GKRS is a valuable, minimally invasive, surgical alternative for idiopathic GPN, with a very high short- and long-term efficacy and without permanent complications. A quality imaging, including T2 CISS/Fiesta MRI and bone CT acquisitions for good visualisation of the nerve and the other bony anatomic landmarks, is essential for targeting accuracy and successful therapy.

An Open-Label, Analgesic Efficacy and Safety of Pituitary Radiosurgery for Patients With Opioid-Refractory Pain: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Hypophysectomy performed by craniotomy or percutaneous techniques leads to complete pain relief in more than 70% to 80% of cases for opioid refractory cancer pain. Radiosurgery could be an interesting alternative approach to reduce complications. OBJECTIVE: To assess the analgesic efficacy compared with standard of care is the primary goal. The secondary objectives are to assess ophthalmic and endocrine tolerance, drug consumption, quality of life, and mechanisms of analgesic action. METHODS: The trial is multicenter, randomized, prospective, and open-label with 2 parallel groups. This concerns patients in palliative care suffering from nociceptive or mixed cancer pain, refractory to standard opioid therapy. Participants will be randomly assigned to the control group receiving standards of care for pain according to recommendations, or to the experimental group receiving a pituitary GammaKnife (Elekta, Stockholm, Sweden) radiosurgery (160 Gy delivered in pituitary gland) associated with standards of care. Evaluation assessments will be taken at baseline, day0, day4, day7, day14, day28, day45, month3, and month6. EXPECTED OUTCOMES: We could expect pain improvement in 70% to 90% of cases at day4. In addition we will assess the safety of pituitary radiosurgery in a vulnerable population. The secondary endpoints could show decay of opioid consumption, good patient satisfaction, and improvement of the quality of life. DISCUSSION: The design of this study is potentially the most appropriate to demonstrate the efficacy and safety of radiosurgery for this new indication. New recommendations could be obtained in order to improve pain relief and quality of life.

Can DTI fiber tracking of the optic radiations predict visual deficit after surgery?

OBJECT: Sparing optic radiations can be of paramount importance during epilepsy surgery of the temporal lobe. The anatomical heterogeneity of the Meyer's loop of the optic radiations could be assessed by means of diffusion tensor tractography. We used temporal lobe surgery as a lesion model to validate this method. MATERIAL AND METHODS: We analyzed the distance between the temporal pole (TP) and Meyer's loop (ML) and the correlation between visual impairment and the percentage of virtual fibers injured. MRI studies were performed in 18 patients and 13 controls. Diffusion tensor imaging (DTI) with fiber tracking was performed using four different algorithms and various gradient directions (15 or 32) and fractional anisotropy (FA) thresholds (0.18, 0.20, and 0.22). To find the best DTI model, we tested each gradient direction and FA threshold on 16 operated patients by pre- and post-operative visual field testing that analyzed the percentage of virtual fibers damaged on 3-month-post-operative MRIs. RESULTS: Marked individual differences were noted in the TP-ML distances (mean: 25.4mm; range 18.2-38.3mm; standard deviation: 4.7) but with no significant difference between patients and controls (p=0.9). The percentage of virtual fibers reconstructed by tracking and damaged by surgery was correlated with visual impairment. Significant differences appeared between algorithm types. The tensor-line algorithm with 15-direction resolution and an anisotropy threshold of 0.18 seemed to be the most relevant. A threshold of 5.5% of injured virtual fiber could predict a visual defect with a sensitivity of 71.4% and a specificity of 87.5%. CONCLUSION: Optic radiation tractography by DTI could be a useful method to assess an individual patient's risk of postoperative visual deficit.

Sentence translation in proficient bilinguals: a direct electrostimulation brain mapping.

Direct cortical electrostimulation was used to study cortical areas hypothetically involved in translation in bilinguals during brain tumour resections, with a view to sparing these functional areas. A series of seven proficient bilingual patients was studied: two left-handed and five right-handed individuals with no pre-existing language deficit. Hemispheric cortex (on the side contralateral to the patient's hand-dominance) was directly stimulated whilst the patient performed naming and reading tasks in both languages and a translation task (of a written text from their second 'learned' language to their first or 'native' language). Of the 147 different cortical sites studied, 26 'language functional sites' were detected, where electrostimulation affected reading and/or naming in the patient's native and/or second learned language. Of these, 8 sites (in 4 patients) were "task-specific" and "language-specific" i.e., affecting only naming or reading in only one of the patient's languages. Of the 26 "language sites", only 3 produced any interferences in translation. All of these were located in frontal regions. Electrostimulation at these sites caused the patient to stop translating abruptly, but no language switching or other translation-related phenomenon was observed. No site was found that was involved only in translation and not other language tasks. Overall, in contrast to other language tasks, cortical structures of the convexity were rarely involved in translation. We suggest that translation interference could be more readily detected by subcortical stimulations. This spatial dissociation within the brain of translation function versus other language functions could explain the cases of dissociated language impairments observed in some bilingual patients with brain lesions. On a practical level, because the cortical sites found by translation tasks are few and related with other cortical language sites, we think that translation tasks provide little additional helpful information for cortical brain mapping in bilingual neurosurgical patients.

Cervical spine injuries resulting from diving accidents in swimming pools: outcome of 34 patients.

Cervical spine injuries after diving into private swimming pools can lead to dramatic consequences. We reviewed 34 patients hospitalized in our center between 1996 and 2006. Data was collected from their initial admission and from follow-up appointments. The injuries were sustained by young men in 97% (mean age 27) and the majority happened during the summer (88%). Fractures were at C5-C7 in 70%. American Spinal Injury Association class (ASIA) on admission was A for 8 patients, B for 4, C for 4, D for 1, and E for 17. There were 23 surgical spine stabilizations. Final ASIA class was A for 6 patients, B for 1, C for 3, D for 5, and E for 18. The mean duration of hospitalization was 21.3 days in our neurosurgical center (mean overall cost: 36,000 Euros/patient) plus 10.6 months in rehabilitation center for the 15 patients admitted who had an ASIA class A to C. Mean overall direct cost for a patient with class A is almost 300,000 Euros, compared to around 10,000 Euros for patients with class D and E. In addition, a profound impact on personal and professional life was seen in many cases including 11 divorces and 7 job losses. Dangerous diving into swimming pools can result in spinal injuries with drastic consequences, including permanent physical disability and a profound impact on socio-professional status. Moreover, there are significant financial costs to society. Better prevention strategies should be implemented to reduce the impact of this public health problem.