David Garcia-Garcia, Jorge Guridi, Jon B. Toledo, Manuel Alegre, José A. Obeso and María C. Rodríguez-Oroz
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely used in patients with Parkinson's disease (PD). However, which target area of this region results in the highest antiparkinsonian efficacy is still a matter of debate. The aim of this study was to develop a more accurate methodology to locate the electrodes and the contacts used for chronic stimulation (active contacts) in the subthalamic region, and to determine the position at which stimulation conveys the greatest clinical benefit.
The study group comprised 40 patients with PD in whom bilateral DBS electrodes had been implanted in the STN. Based on the Morel atlas, the authors created an adaptable 3D atlas that takes into account individual anatomical variability and divides the STN into functional territories. The locations of the electrodes and active contacts were obtained from an accurate volumetric assessment of the artifact using preoperative and postoperative MR images. Active contacts were positioned in the 3D atlas using stereotactic coordinates and a new volumetric method based on an ellipsoid representation created from all voxels that belong to a set of contacts. The antiparkinsonian benefit of the stimulation was evaluated by the reduction in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score and in the levodopa equivalent daily dose (LEDD) at 6 months. A homogeneous group classification for contact position and the respective clinical improvement was applied using a hierarchical clustering method.
Subthalamic stimulation induced a significant reduction of 58.0% ± 16.5% in the UPDRS-III score (p < 0.001) and 64.9% ± 21.0% in the LEDD (p < 0.001). The greatest reductions in the total and contralateral UPDRS-III scores (64% and 76%, respectively) and in the LEDD (73%) were obtained when the active contacts were placed approximately 12 mm lateral to the midline, with no influence of the position being observed in the anteroposterior and dorsoventral axes. In contrast, contacts located about 10 mm from the midline only reduced the global and contralateral UPDRS-III scores by 47% and 41%, respectively, and the LEDD by 33%. Using the ellipsoid method of location, active contacts with the highest benefit were positioned in the rostral and most lateral portion of the STN and at the interface between this subthalamic region, the zona incerta, and the thalamic fasciculus. Contacts placed in the most medial regions of the motor STN area provided the lowest clinical efficacy.
The authors report an accurate new methodology to assess the position of electrodes and contacts used for chronic subthalamic stimulation. Using this approach, the highest antiparkinsonian benefit is achieved when active contacts are located within the rostral and the most lateral parts of the motor region of the STN and at the interface of this region and adjacent areas (zona incerta and thalamic fasciculus).
Juan Sahuquillo-Barris, Jose Lamarca-Ciuro, Jorge Vilalta-Castan, Enrique Rubio-Garcia and Manuel Rodriguez-Pazos
✓ The association of acute subdural hematoma (SDH) and diffuse axonal injury has received little attention in the literature. The authors report the clinicopathological findings in six patients who died of severe head injury in whom computerized tomography revealed acute SDH as the predominant lesion. All patients were injured in road traffic accidents and lost consciousness on impact. The mean total contusion index was 17.4 and severe contusions were seen in only two cases. All patients presented histological criteria of intracranial hypertension (pressure necrosis focus in one or both parahippocampal gyri). Hypoxic brain damage was evident in the postmortem examination of three patients. In three cases, macroscopic hematic lesions were observed in the corpus callosum. All patients had widespread axonal retraction balls disseminated in the white brain matter. Three patients who survived for more than 11 days had microglial clusters. In some patients with a head injury, acute SDH may be only an epiphenomenon of a primary impact lesion of variable severity: that is, a diffuse axonal injury. In these cases, the final outcome is fundamentally dependent on the severity of the subjacent diffuse axonal injury.
Eudaldo M. López-Tomassetti Fernández, Juan Ramón Hernández Hernández, Jose Ceballos Esparragon, Angel Turegano García and Valentin Nuñez Jorge
The authors report the case of a 50-year-old woman with a benign intermuscular lipoma of the gluteus compressing the sciatic nerve in its course through the sciatic notch. This benign soft-tissue tumor extended into the pelvis, displacing the rectum laterally. Resection was necessary to alleviate symptoms and prevent irreversible damage of the nerve. Wide exposure of the piriformis muscle and sciatic nerve via a transgluteal approach allowed safe lesion removal, and thus avoiding a laparotomy to resect the intrapelvic extension of the tumor. This report features a curious case of soft-tissue tumor growth across the sciatic foramen forming an inverted sciatic hernia. The authors' proposed approach was simple and safe and avoided a laparotomy.
Jorge Eduardo Duque Parra, John Barco Ríos and Jhonny Fernando García Aguirre
Olga Helena Hernández Ortiz, Héctor Iván García García, Fabián Muñoz Ramírez, Juan Sebastián Cardona Flórez, Bladimir Alejandro Gil Valencia, Salvador Ernesto Medina Mantilla, María Juliana Moreno Ochoa, Jorge Eliécer Sará Ochoa and Fabián Jaimes
Diagnosing nosocomial meningitis (NM) in neurosurgical patients is difficult. The standard CSF test is not optimal and when it is obtained, CSF cultures are negative in as many as 70% of cases. The goal of this study was to develop a diagnostic prediction rule for postoperative meningitis using a combination of clinical, laboratory, and CSF variables, as well as risk factors (RFs) for CNS infection.
A cross-sectional study was performed in 4 intensive care units in Medellín, Colombia. Patients with a history of neurosurgical procedures were selected at the onset of febrile symptoms and/or after an increase in acute-phase reactants. Their CSF was studied for suspicion of infection and a bivariate analysis was performed between the dependent variable (confirmed/probable NM) and the identified independent variables. Those variables with a p value ≤ 0.2 were fitted in a multiple logistic regression analysis with the same dependent variable. After determining the best model according to its discrimination and calibration, the β coefficient for each selected dichotomized variable obtained from the logistic regression model was used to construct the score for the prediction rule.
Among 320 patients recruited for the study, 154 had confirmed or probable NM. Using bivariate analysis, 15 variables had statistical associations with the outcome: aneurysmal subarachnoid hemorrhage (aSAH), traumatic brain injury, CSF leak, positioning of external ventricular drains (EVDs), daily CSF draining via EVDs, intraventricular hemorrhage, neurological deterioration, age ≥ 50 years, surgical duration ≥ 220 minutes, blood loss during surgery ≥ 200 ml, C-reactive protein (CRP) ≥ 6 mg/dl, CSF/serum glucose ratio ≤ 0.4 mmol/L, CSF lactate ≥ 4 mmol/L, CSF leukocytes ≥ 250 cells, and CSF polymorphonuclear (PMN) neutrophils ≥ 50%. The multivariate analysis fitted a final model with 6 variables for the prediction rule (aSAH diagnosis: 1 point; CRP ≥ 6 mg/dl: 1 point; CSF/serum glucose ratio ≤ 0.4 mmol/L: 1 point; CSF leak: 1.5 points; CSF PMN neutrophils ≥ 50%: 1.5 points; and CSF lactate ≥ 4 mmol/L: 4 points) with good calibration (Hosmer-Lemeshow goodness of fit = 0.71) and discrimination (area under the receiver operating characteristic curve = 0.94).
The prediction rule for diagnosing NM improves the diagnostic accuracy in neurosurgical patients with suspicion of infection. A score ≥ 6 points suggests a high probability of neuroinfection, for which antibiotic treatment should be considered. An independent validation of the rule in a different group of patients is warranted.
Jesús A. Morales-Gómez, Everardo Garcia-Estrada, Jorge E. Leos-Bortoni, Miriam Delgado-Brito, Luis E. Flores-Huerta, Adriana A. De La Cruz-Arriaga, Luis J. Torres-Díaz and Ángel R. Martínez-Ponce de León
Cranioplasty implants should be widely available, low in cost, and customized or easy to mold during surgery. Although autologous bone remains the first choice for repair, it cannot always be used due to infection, fragmentation, bone resorption, or other causes, which led to use of synthetic alternatives. The most frequently used allogenic material for cranial reconstructions with long-term results is polymethylmethacrylate (PMMA). Three-dimensional printing technology has allowed the production of increasingly popular customized, prefabricated implants. The authors describe their method and experience with a customized PMMA prosthesis using a precise and reliable low-cost implant that can be customized at any institution with open-source or low-cost software and desktop 3D printers.
A review of 22 consecutive patients undergoing CT-based, low-cost, customized PMMA cranioplasty over a 1-year period at a university teaching hospital was performed. Preoperative data included patient sex and age; CT modeling parameters, including the surface area of the implant (defect); reason for craniectomy; date(s) of injury and/or resections; the complexity of the defect; and associated comorbidities. Postoperative data included morbiditiy and complications, such as implant exposure, infection, hematoma, seroma, implant failure, and seizures; the cost of the implant; and cosmetic outcome.
Indications for the primary craniectomy were traumatic brain injury (16, 73%), tumor resection (3, 14%), infection (1, 4%), and vascular (2, 9%). The median interval between previous surgery and PMMA cranioplasty was 12 months. The operation time ranged from 90 to 150 minutes (mean 126 minutes). The average cranial defect measured 65.16 cm2 (range 29.31–131.06 cm2). During the recovery period, there was no sign of infection, implant rejection, or wound dehiscence, and none of the implants had to be removed over a follow-up ranging from 1 to 6 months. The aesthetic appearance of all patients was significantly improved, and the implant fit was excellent.
The use of a customized PMMA was associated with excellent patient, family, and surgeon satisfaction at follow-up at a fraction of the cost associated with commercially available implants. This technique could be an attractive option to all patients undergoing cranioplasty.
Jacob A. Miller, Ehsan H. Balagamwala, Lilyana Angelov, John H. Suh, Brian Rini, Jorge A. Garcia, Manmeet Ahluwalia and Samuel T. Chao
Systemic control of metastatic renal cell carcinoma (mRCC) has substantially improved with the development of VEGF, mTOR, and checkpoint inhibitors. The current first-line standard of care is a VEGF tyrosine kinase inhibitor (TKI). In preclinical models, TKIs potentiate the response to radiotherapy. Such improved efficacy may prolong the time to salvage therapies, including whole-brain radiotherapy or second-line systemic therapy.
As the prevalence of mRCC has increased, the utilization of spine stereotactic radiosurgery (SRS) has also increased. However, clinical outcomes following concurrent treatment with SRS and TKIs remain largely undefined. The purpose of this investigation was to determine the safety and efficacy of TKIs when delivered concurrently with SRS. The authors hypothesized that first-line TKIs delivered concurrently with SRS significantly increase local control compared with SRS alone or TKIs alone, without increased toxicity.
A retrospective cohort study of patients undergoing spine SRS for mRCC was conducted. Patients undergoing SRS were divided into 4 cohorts: those receiving concurrent first-line TKI therapy (A), systemic therapy–naïve patients (B), and patients who were undergoing SRS with (C) or without (D) concurrent TKI treatment after failure of first-line therapy. A negative control cohort (E) was also included, consisting of patients with spinal metastases managed with TKIs alone. The primary outcome was 12-month local failure, defined as any in-field radiographic progression. Multivariate competing risks regression was used to determine the independent effect of concurrent first-line TKI therapy upon local failure.
One hundred patients who underwent 151 spine SRS treatments (232 vertebral levels) were included. At the time of SRS, 46% were receiving concurrent TKI therapy. In each SRS cohort, the median prescription dose was 16 Gy in 1 fraction. Patients in Cohort A had the highest burden of epidural disease (96%, p < 0.01).
At 12 months, the cumulative incidence of local failure was 4% in Cohort A, compared with 19%–27% in Cohorts B–D and 57% in Cohort E (p < 0.01). Multivariate competing risks regression demonstrated that concurrent first-line TKI treatment (Cohort A) was independently associated with a local control benefit (HR 0.21, p = 0.04). In contrast, patients treated with TKIs alone (Cohort E) experienced an increased rate of local failure (HR 2.43, p = 0.03). No toxicities of Grade 3 or greater occurred following SRS with concurrent TKI treatment, and the incidence of post-SRS vertebral fracture (overall 21%) and pain flare (overall 17%) were similar across cohorts.
The prognosis for patients with mRCC has significantly improved with TKIs. The present investigation suggests a local control benefit with the addition of concurrent first-line TKI therapy to spine SRS. These results have implications in the oligometastatic setting and support a body of preclinical radiobiological research.
Gabriel F. Santiago, Amir Wolff, Micah Belzberg and Chad R. Gordon
Aditya Juloori, Jacob A. Miller, Shireen Parsai, Rupesh Kotecha, Manmeet S. Ahluwalia, Alireza M. Mohammadi, Erin S. Murphy, John H. Suh, Gene H. Barnett, Jennifer S. Yu, Michael A. Vogelbaum, Brian Rini, Jorge Garcia, Glen H. Stevens, Lilyana Angelov and Samuel T. Chao
The object of this retrospective study was to investigate the impact of targeted therapies on overall survival (OS), distant intracranial failure, local failure, and radiation necrosis among patients treated with radiation therapy for renal cell carcinoma (RCC) metastases to the brain.
All patients diagnosed with RCC brain metastasis (BM) between 1998 and 2015 at a single institution were included in this study. The primary outcome was OS, and secondary outcomes included local failure, distant intracranial failure, and radiation necrosis. The timing of targeted therapies was recorded. Multivariate Cox proportional-hazards regression was used to model OS, while multivariate competing-risks regression was used to model local failure, distant intracranial failure, and radiation necrosis, with death as a competing risk.
Three hundred seventy-six patients presented with 912 RCC BMs. Median OS was 9.7 months. Consistent with the previously validated diagnosis-specific graded prognostic assessment (DS-GPA) for RCC BM, Karnofsky Performance Status (KPS) and number of BMs were the only factors prognostic for OS. One hundred forty-seven patients (39%) received vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Median OS was significantly greater among patients receiving TKIs (16.8 vs 7.3 months, p < 0.001). Following multivariate analysis, KPS, number of metastases, and TKI use remained significantly associated with OS.
The crude incidence of local failure was 14.9%, with a 12-month cumulative incidence of 13.4%. TKIs did not significantly decrease the 12-month cumulative incidence of local failure (11.4% vs 14.5%, p = 0.11). Following multivariate analysis, age, number of BMs, and lesion size remained associated with local failure. The 12-month cumulative incidence of radiation necrosis was 8.0%. Use of TKIs within 30 days of SRS was associated with a significantly increased 12-month cumulative incidence of radiation necrosis (10.9% vs 6.4%, p = 0.04).
Use of targeted therapies in patients with RCC BM treated with intracranial SRS was associated with improved OS. However, the use of TKIs within 30 days of SRS increases the rate of radiation necrosis without improving local control or reducing distant intracranial failure. Prospective studies are warranted to determine the optimal timing to reduce the rate of necrosis without detracting from survival.