Brain metastasis treatment guidelines: consensus by the Spanish Society of Neurosurgery Tumor Section.

Brain metastases are tumors that arise from a tumor cell originated in another organ reaching the brain through the blood. In the brain this tumor cell is capable of growing and invading neighboring tissues, such as the meninges and bone. In most patients a known tumor is present when the brain lesion is diagnosed, although it is possible that the first diagnose is the brain tumor before there is evidence of cancer elsewhere in the body. For this reason, the neurosurgeon must know the management that has shown the greatest benefit for brain metastasis patients, so treatments can be streamlined and optimized. Specifically, in this document, the following topics will be developed: selection of the cancer patient candidate for surgical resection and the role of the neurosurgeon in the multidisciplinary team, the importance of immunohistological and molecular diagnosis, surgical techniques, radiotherapy techniques, treatment updates of chemotherapy and immunotherapy and management algorithms in brain metastases. With this consensus manuscript, the tumor group of the Spanish Society of Neurosurgery (GT-SENEC) exposes the most relevant neurosurgical issues and the fundamental aspects to harmonize multidisciplinary treatment, especially with the medical specialties that are treating or will treat these patients.

Long-term Experience of LINAC Single-Dose Radiosurgery for Skull Base Meningiomas: A Retrospective Single-Center Study of 241 Cases.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is increasingly applied to treat meningiomas, attributable to their increased incidence in older individuals at greater surgical risk. To evaluate the effectiveness of treatment with linear accelerator (LINAC)-based stereotactic radiosurgery in skull base meningiomas as either primary treatment or postresection adjuvant therapy. METHODS: This study included 241 patients diagnosed with skull base meningiomas treated by single-dose SRS, with a median age of 59 years. SRS was primary treatment in 68.1% (n = 164) and adjuvant treatment in 31.9% (n = 77), using LINAC (Varian 600, 6 MeV). The median tumor volume was 3.2 cm 3 , and the median coverage dose was 14 Gy. Bivariate and multivariate analyses were performed to determine predictive factors for tumor progression, clinical deterioration, and complications. Kaplan-Meier analysis was used for survival analysis. RESULTS: After the median follow-up of 102 months, the tumor control rate was 91.2% (n = 220). Progression-free survival rates were 97.07%, 90.1%, and 85.7% at 5, 10, and 14 years, respectively. Clinical improvement was observed in 56 patients (23.2%). In multivariate analysis, previous surgery (hazard ratio 3.8 [95%CI 1.136-12.71], P = .030) and selectivity (hazard ratio .21 [95%CI 0.066-0.677], P = .009) were associated with tumor progression and increased maximum dose (odds ratio [OR] 4.19 [95% CI 1.287-13.653], P = .017) with clinical deterioration. The permanent adverse radiation effect rate was 6.2% (n = 15) and associated with maximum brainstem dose >12.5 Gy (OR 3.36 [95% CI .866-13.03], P = .08) and cerebellopontine angle localization (OR 3.93 [95% CI 1.29-11.98], P = .016). CONCLUSION: Treatment of skull base meningiomas with single-dose SRS using LINAC is effective over the long term. Superior tumor control is obtained in patients without previous surgery. Adverse effects are related to localization in the cerebellopontine angle, and maximum brainstem radiation dose was >12.5 Gy.

Cerebellopontine angle meningiomas: LINAC stereotactic radiosurgery treatment.

OBJECTIVES: To evaluate the efficacy of treatment with linear accelerator-based stereotactic radiosurgery (LINAC) in cerebellopontine angle meningiomas. METHODS: We analyzed 80 patients diagnosed with cerebellopontine angle meningiomas between 2001 and 2014, treated with stereotactic radiosurgery (SRS), of whom 81.9% (n=68) were women, with an average age of 59.1 years (32-79). SRS was applied as primary treatment in 83.7% (n=67) and in 16.3% (n=13) as an adjuvant treatment to surgery. SRS treatment was provided using LINAC (Varian 600, 6MeV) with M3 micromultilamines (brainLab) and stereotactic frame. The average tumor volume was 3.12cm3 (0.34-10.36cm3) and the coverage dose was 14Gy (12-16Gy). We performed a retrospective descriptive analysis and survival analysis was performed with the Kaplan-Meier method and multivariate analysis to determine those factors predictive of tumor progression or clinical improvement. RESULTS: After an average follow-up period of 86.9 months (12-184), the tumor control rate was 92.8% (n=77). At the end of the study, there was an overall reduction in tumor volume of 32.8%, with an average final volume of 2.11cm3 (0-10.35cm3). The progression-free survival rate at 5, 10 and 12 years was 98%, 95% and 83.3% respectively. The higher tumor volume (p=0.047) was associated with progression. There was clinical improvement in 26.5% (n=21) of cases and clinical worsening in 16.2% (n=13). Worsening is related to the radiation dose received by the brainstem (p=0.02). Complications were 8.7% (7 cases) of hearing loss, 5% (4 cases) of brain radionecrosis, and 3.7% (3 cases) of cranial nerve V neuropathy. Hearing loss was related to initial tumor size (p=0.033) and maximum dose (p=0.037). The occurrence of radionecrosis with the maximum dose (p=0.037). CONCLUSIONS: Treatment of cerebellopontine angle meningiomas with single-dose SRS using LINAC is effective in the long term. Better tumor control rates were obtained in patients with small lesions.

High-frequency spinal cord stimulation as rescue therapy for chronic pain patients with failure of conventional spinal cord stimulation.

BACKGROUND: This study aims to evaluate the efficacy of 10-kHz high-frequency (HF10) devices as a rescue treatment in patients with failure of conventional spinal cord stimulation (SCS) therapy for chronic pain without the need to change the spinal hardware. METHODS: In this real-world prospective study, patients with neuropathic pain treated with conventional tonic SCS in whom the therapy had failed, either during the trial phase or after a period of optimal functioning, were recruited throughout 2 years for HF10-SCS therapy. Data on analgesia, functionality, analgesics use and treatment safety were collected 12 months after treatment. RESULTS: Eleven of the 18 (61%) patients included in the study were successfully rescued with HF10-SCS. Of them, 5 out of 12 (45%) were in the trial phase and six out of six (100%) had previously functioning implants. A significant improvement in low-back and limb pain was obtained (p = 0.003 and p = 0.0001, respectively). Treatment success was significantly associated with gender (p = 0.037), weight (p = 0.014), body mass index (BMI) (p = 0.007) and time of rescue (p = 0.015). A linear regression test confirmed a significant association between treatment failure and BMI and gender (p = 0.004). CONCLUSIONS: Our results suggest that analgesic rescue with HF10-SCS is an effective therapeutic option for non-responders to conventional SCS, although obesity might be a limiting factor for treatment success. Nevertheless, more comprehensive studies are needed to corroborate our findings. SIGNIFICANCE: This study shows that high-frequency stimulation may be useful in patients with failure of conventional tonic stimulation for chronic pain, both in the trial phase and in previously implanted subjects. The novelty of this study lies in the use of the implanted epidural electrodes, which avoids the need for further surgery. The results in terms of pain control and recovery of functionality are satisfactory. In addition, variables such as male gender and high body mass index could be predictors of therapy failure.

[Clinical and pathological definition of temporal medium epilepsy subtypes with hypocampic sclerosis]. / Definición clínico-patológica de los subtipos de epilepsia temporal medial con esclerosis del hipocampo.

BACKGROUND AND OBJECTIVE: Mesial temporal lobe epilepsy with hippocampal sclerosis is the most common cause of refractory epilepsy, and the most common indication for surgery. Although effective, surgery fails in up to 40% of patients. The objective of our study was to establish a correlation between the different histological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis and the prognosis, seizures control, side effects and anticonvulsivant drug withdrawal in patients with refractory epilepsy. PATIENTS AND METHOD: Clinical histories and anatomopathological specimens of 228 patients with temporal epilepsy surgically obtained at our hospital between 1993 and 2014 were retrospectively analysed. All patients underwent a standard preoperative evaluation and anterior temporal resection (modified from Spencer). The anatomopathological study included the standard hematoxylin-eosin and immunohistochemical protocol, with special interest in the assessment of neuronal loss with NeuN. Seizure control was assessed according to the scale of results of the ILAE and Engel. The mean follow-up was 8.6 years (2-19). RESULTS: At 10 years after the intervention, 67.9% of patients were seizure-free (ILAE 1) and as many as 77.5% of the patients were seizure-free (Engel 1) at the end of the follow-up. The probability of not having a seizure (ILAE 1) after surgery at 2 (p=.042), 5 (p=.001) and 7 years (p=.22) was higher in classic and severe forms compared to isolated sclerosis CA1 and CA4 forms. Higher neuronal loss measured with the NeuN immunostain in CA1 was associated with better outcome in seizure management (multivariate analysis, p=.08). The presence of a personal history of epilepsy was associated with greater neuronal loss in CA1 (p=.028) and CA3 (p=.034), and the presence of psychic auras was related with greater neuronal loss in CA3 (p=.025). In our case, the probability of medication withdrawal was related to the presence of personal history (p=.003) and, inversely, to neuronal loss in CA1 (p=.036) and CA3 (p=.038). The greatest impairment of verbal memory occurred in those patients with a lower neuronal loss in CA1 (p=.023), CA2 (p=.049) and CA3 (p=.035). CONCLUSIONS: The results indicate that the classical and severe subtypes have a better prognosis in the control of seizures against the atypical forms, validating the clinical and prognostic utility of the classification of histological subtypes of hippocampal sclerosis from the ILAE. The value of the immunohistochemistry in the mesial temporal lobe epilepsy with hippocampal sclerosis has been demonstrated as a key element to determine the neuropsychological prognosis and seizure management of the patients after surgery.

¹8F-Fluorocholine PET/CT as a complementary tool in the follow-up of low-grade glioma: diagnostic accuracy and clinical utility.

PURPOSE: The follow-up of treated low-grade glioma (LGG) requires the evaluation of subtle clinical changes and MRI results. When the result is inconclusive, additional procedures are required to assist decision-making, such as the use of advanced MRI (aMRI) sequences and nuclear medicine scans (SPECT and PET). The aim of this study was to determine whether incorporating (18)F-fluorocholine PET/CT in the follow-up protocol for treated LGG improves diagnostic accuracy and clinical utility. METHODS: This was a prospective case-series study in patients with treated LGG during standard follow-up with indeterminate clinical and/or radiological findings of tumour activity. All patients underwent clinical evaluation, aMRI, (201)Tl-SPECT and (18)F-fluorocholine PET/CT. Images were interpreted by visual evaluation complemented with semiquantitative analysis. RESULTS: Between January 2012 and December 2013, 18 patients were included in this study. The final diagnosis was established by histology (five surgical specimens, one biopsy specimen) or by consensus of the Neuro-Oncology Group (11 patients) after a follow-up of >6 months (mean 14.9 ± 2.72 months). The global diagnostic accuracies were 90.9% for aMRI (38.8% inconclusive), 69.2 % for (201)Tl-SPECT (11.1% inconclusive), and 100% for (18)F-fluorocholine PET/CT. (201)Tl-SPECT led correctly to a change in the initial approach in 38.9% of patients but might have led to error in 27.8%. The use of (18)F-fluorocholine PET/CT alone rather than (201)Tl-SPECT led correctly to a change in the approach suggested by routine follow-up in 72.2% of patients and endorsed the approach in the remaining 27.8%. CONCLUSION: Our results support the need to complement structural MRI with aMRI and nuclear medicine procedures in selected patients. (18)F-Fluorocholine PET/CT can be useful in the individualized management of patients with treated LGG with uncertain clinical and/or radiological evidence of tumour activity.

Angiographic characteristics of epileptogenic arteriovenous malformations and effectiveness in the seizure control after treatment with radiosurgery.

OBJETIVE: Define the angiographic characteristics of epileptogenic arteriovenous malformations (AVM) and assess symptom control of the seizure after treatment with radiosurgery. MATERIAL AND METHODS: Between 1996 and 2006, a total of 237 adults patients were diagnosed with AVM and were treated in our center by radiosurgery with linear accelerator. We analyzed demographics, clinicals, angiographics and radiosurgicals characteristics and the complications of the procedure in each of them. The first symptom was a seizure in 68 of them and the subsequent analysis of the treatment effectiveness for the seizure control was done, and the possible predictive factors of AVM nidus evolution were assessed. RESULT: The average volume of the epileptogenic AVMs was 7.17 cc, compared ot the non-epileptogenic AVM 5.06 cc (p<0.03). Other differentiating factors were surface blood supply (p<0.003), venous ectasia (p<0.064), angiogenesis (p<0.078), and the presence of unrelated aneurysms (p<0.08). For 68 patients (28.7%) with seizures a clinical control (Seizure Frequency Scoring System SFSS ≤2) was obtained in 70% of patients and there was an excellent control (SFSS ≤1) in 25% of them. The percent occlusion of their AVMs was 50%. There was statistical significance with SFSS ≤1 (p<0.01), but was not any significance with SFSS ≤2. Age (p<0.003) and diffuse nidus morphology (p<0.05) were predictors of good AVM nidus evolution. CONCLUSIONS: The stereotactic radiosurgery seems to be an effective method for control of symptomatic seizures for intracranial AVMs. Certain angiographic characteristics, such as the volume, surface blood supply, angiogenesis, venous ectasia, and unrelated aneurysms to the AVMs, seem to influence the appearance of epileptic seizures.

[Adult chronic idiopathic hydrocephalus-diagnosis, treatment and evolution. Prospective study]. / Hidrocefalia crónica del adulto: diagnóstico, tratamiento y evolución. Estudio prospectivo.

INTRODUCTION: At present, chronic hydrocephalus or normal pressure hydrocephalus (NPH) has a controversial diagnosis in which multiple diagnostic and therapeutic techniques have been used with variable degrees of postoperative success. The aim of our study is to evaluate a number of patients diagnosed with adult chronic idiopathic hydrocephalus who were treated with a CSF shunt at our centre between 2006 and 2009 through clinical scales and radiological controls pre- and postoperatively. MATERIAL AND METHODS: We prospectively analysed 40 patients. The diagnosis of idiopathic NPH was established when patients met 3 criteria: (i)clinical; (ii)radiological (Evans >0.3), and (iii)hydrodynamic (Katzman infusion test with Rout >12) or pathological ICP monitoring (B waves in over 20% of a nocturnal registration). We used a low-pressure DVP 5/35 GAV in all cases. Clinical assessments were conducted at 3, 6 and 12 months and radiological assessments at 6 months postoperatively. The clinical improvement of patients was assessed with the NPH, modified RANKIN and modified PFEIFFER rating scales. RESULTS: The study of risk factors (age, gender, smoking, drinking, arterial hypertension, diabetes mellitus, dyslipidemia) did not establish statistically significant relationships. A statistically significant improvement was observed (P<.01) in the NPH and RANKIN tests at 3, 6 and 12 months. Clinical improvement values obtained were: NPH 73%, 74% and 64%, and RANKIN 54%, 72% and 56%, respectively. The PFEIFFER scale only showed a significant improvement at 12 months. These improvements were classified into various levels (high, moderate, mild and no improvement). The initial mean Evans index was 0.385, and 0.3675 postoperatively. There was only one infection of the valvular system (2%) without further complications. Morbidity and mortality related to the procedure were 0%. CONCLUSION: An appropriate selection of patients through clinical, radiological, hydrodynamic and ICP monitoring criteria enables us to obtain good results and a low complication rate.

[Primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors: Group for the Study of Functional-Sterotactic Neurosurgery of The Spain Society of Neurosurgery recommendations]. / Control de las crisis epilépticas durante el postoperatorio inmediato de los tumores cerebrales supratentoriales: recomendaciones del Grupo de Neurocirugía Funcional y Estereotáctica de la Sociedad Española de Neurocirugía.

Our review of the literature is basically focused on the primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors, with the aim of suggesting several recommendations in medical antiepileptic treatment to avoid this kind of seizures which occur immediately after surgery. In conclusion, it is recommended to provide criteria for prophylaxis of early seizures after surgery of cerebral supratentorial tumors. It́s recommended a one week treatment with antiepileptic drugs in patients who didnt have seizures jet, starting immediately after the surgical treatment. If seizures appear during progress of the disease, a large period treatment will be needed. Preferred antiepileptic treatment is intravenous and with a low interactions profile. Levetiracetam, followed by valproic acid seem to be most appropriated drugs due to their properties and protective effects, particularly for our patients requirements. These recommendations are considered a general proposal to effective clinical management of early seizures after surgery, not taking into account the single circumstances of our patients. Always, clinical features of the patients could modify even significantly these guides in the benefit of each patient.