Surgically targeted radiation therapy (STaRT) for recurrent brain metastases: Initial clinical experience.

PURPOSE: This study evaluates the outcomes of recurrent brain metastasis treated with resection and brachytherapy using a novel Cesium-131 carrier, termed surgically targeted radiation therapy (STaRT), and compares them to the first course of external beam radiotherapy (EBRT). METHODS: Consecutive patients who underwent STaRT between August 2020 and June 2022 were included. All patients underwent maximal safe resection with pathologic confirmation of viable disease prior to STaRT to 60 Gy to a 5-mm depth from the surface of the resection cavity. Complications were assessed using CTCAE version 5.0. RESULTS: Ten patients with 12 recurrent brain metastases after EBRT (median 15.5 months, range: 4.9-44.7) met the inclusion criteria. The median BED10Gy90% and 95% were 132.2 Gy (113.9-265.1 Gy) and 116.0 Gy (96.8-250.6 Gy), respectively. The median maximum point dose BED10Gy for the target was 1076.0 Gy (range: 120.7-1478.3 Gy). The 6-month and 1-year local control rates were 66.7% and 33.3% for the prior EBRT course; these rates were 100% and 100% for STaRT, respectively (p < 0.001). At a median follow-up of 14.5 months, there was one instance of grade two radiation necrosis. Surgery-attributed complications were observed in two patients including pseudomeningocele and minor headache. CONCLUSIONS: STaRT with Cs-131 presents an alternative approach for operable recurrent brain metastases and was associated with superior local control than the first course of EBRT in this series. Our initial clinical experience shows that STaRT is associated with a high local control rate, modest surgical complication rate, and low radiation necrosis risk in the reirradiation setting.

Surgery, Stereotactic Radiosurgery, and Systemic Therapy in the Management of Operable Brain Metastasis.

Brain metastasis represents the most common intracranial tumor. Surgery has a key role in patients with an unknown primary, solitary site, large intracranial lesion, or those with neurologic symptomatology due to associated vasogenic edema and mass effect. There is also a resurgence in interest in biopsy or resection in patients with actionable alterations with discordant responses to targeted therapy or those proceeding to immunotherapy to reduce corticosteroid requirements. Moreover, advancements in radiotherapy have led to several options in patients with resectable brain metastasis including postoperative whole-brain radiotherapy, postoperative stereotactic radiosurgery (SRS), preoperative SRS, intraoperative radiotherapy, and CNS brachytherapy.

Evaluation of the impact of pre-operative stereotactic radiotherapy on the acute changes in histopathologic and immune marker profiles of brain metastases.

The unique acute effects of the large fractional doses that characterize stereotactic radiosurgery (SRS) or radiotherapy (SRT), specifically in terms of antitumor immune cellular processes, vascular damage, tumor necrosis, and apoptosis on brain metastasis have yet to be empirically demonstrated. The objective of this study is to provide the first in-human evaluation of the acute biological effects of SRS/SRT in resected brain metastasis. Tumor samples from patients who underwent dose-escalated preoperative SRT followed by resection with available non-irradiated primary tumor tissues were retrieved from our institutional biorepository. All primary tumors and irradiated metastases were evaluated for the following parameters: tumor necrosis, T-cells, natural killer cells, vessel density, vascular endothelial growth factor, and apoptotic factors. Twenty-two patients with irradiated and resected brain metastases and paired non-irradiated primary tumor samples met inclusion criteria. Patients underwent a median preoperative SRT dose of 18 Gy (Range: 15-20 Gy) in 1 fraction, with 3 patients receiving 27-30 Gy in 3-5 fractions, followed by resection within median interval of 67.8 h (R: 18.25-160.61 h). The rate of necrosis was significantly higher in irradiated brain metastases than non-irradiated primary tumors (p < 0.001). Decreases in all immunomodulatory cell populations were found in irradiated metastases compared to primary tumors: CD3 + (p = 0.003), CD4 + (p = 0.01), and CD8 + (p = 0.01). Pre-operative SRT is associated with acute effects such as increased tumor necrosis and differences in expression of immunomodulatory factors, an effect that does not appear to be time dependent, within the limited intervals explored within the context of this analysis.

The Vagus Nerve Somatosensory-evoked Potential in Neural Disorders: Systematic Review and Illustrative Vignettes.

Objective. To review the scientific publications reporting vagal nerve somatosensory-evoked potential (VSEP) findings from individuals with brain disorders, and present novel physiological explanations on the VSEP origin. Methods. We did a systematic review on the papers reporting VSEP findings from individuals with brain disorders and their controls. We evaluated papers published from 2003 to date indexed in PubMed, Web of Science, and Scielo databases. We extracted the following information: number of patients and controls, type of neural disorder, age, gender, stimulating/recording and grounding electrodes as well as stimulus side, intensity, duration, frequency, and polarity. Information about physiological parameters, neurobiological variables, and correlation studies was also reviewed. Representative vignettes were included to add support to our conclusions. Results. The VSEP was studied in 297 patients with neural disorders such as Parkinson's disease (PD), Alzheimer's disease, vascular dementia, mild cognitive impairment, subjective memory impairment, major depression, and multiple sclerosis. Scalp responses marked as the VSEP showed high variability, low validity, and poor reproducibility. VSEP latencies and amplitudes did not correlate with disease duration, unified PD rating scale score, or heart function in PD patients nor with cerebrospinal fluid ß amyloid, phosphor-τ, and cognitive tests from patients with mental disorders. Vignettes demonstrated that the VSEP was volume conduction propagating from muscles surrounding the scalp recording electrodes. Conclusion. The VSEP is not a brain-evoked potential of neural origin but muscle activity induced by electrical stimulation of the tragus region of the ear. This review and illustrative vignettes argue against assessing the parasympathetic system using the so-called VSEP.

Factors associated with unplanned readmissions and costs following resection of brain metastases in the United States.

The purpose of this study was to critically analyze the risk of unplanned readmission following resection of brain metastasis and to identify key risk factors to allow for early intervention strategies in high-risk patients. We analyzed data from the Nationwide Readmissions Database (NRD) from 2010-2014, and included patients who underwent craniotomy for brain metastasis, identified using ICD-9-CM diagnosis (198.3) and procedure (01.59) codes. The primary outcome of the study was unplanned 30-day all-cause readmission rate. Secondary outcomes included reasons and costs of readmissions. Hierarchical logistic regression model was used to identify the factors associated with 30-day readmission following craniotomy for brain metastasis. During the study period, 44,846 index hospitalizations occurred for patients who underwent resection of brain metastasis. In this cohort, 17.8% (n = 7,965) had unplanned readmissions within the first 30 days after discharge from the index hospitalization. The readmission rate did not change significantly during the five-year study period (p-trend = 0.286). The median per-patient cost for 30-day unplanned readmission was $11,109 and this amounted to a total of $26.4 million per year, which extrapolates to a national expenditure of $269.6 million. Increasing age, male sex, insurance status, Elixhauser comorbidity index, length of stay, teaching status of the hospital, neurological complications and infectious complications were associated with 30-day readmission following discharge after an index admission for craniotomy for brain metastasis. Unplanned readmission rates after resection of brain metastasis remain high and involve substantial healthcare expenditures. Developing tools and interventions to prevent avoidable readmissions could focus on the high-risk patients as a future strategy to decrease substantial healthcare expense.

The last decade's experience of management of central neurocytomas: Treatment strategies and new options.

BACKGROUND: The purpose of the presented work is to evaluate the last decade's experience in surgical management of central neurocytoma (CN) and elucidate on the treatment strategies and new options. METHODS: The current series consists of the remaining 125 patients (70 females and 55 males) operated on during the past decade from 2008 to 2018. Most tumors were resected through transcortical (n = 76, 61%), or transcallosal (n = 40, 32%) approaches. In 5 (4%) patients with predominantly posterior location of the tumor, non-dominant superior parietal lobule approach was utilized. Both approaches (transcortical + transcallosal) were used in 4 (3%) of cases. Seven consecutive patients with large CN underwent prophylactic intraventricular stenting to prevent hydrocephalus. RESULTS: Gross total resection was achieved in 45 patients (36%), subtotal resection (STR) in 40 (32%) cases. After surgery, 63 (50%) patients had neurocognitive problems, including disorientation, attention deficit, global amnesia, short-term memory deficits, and perceptual motor and social cognition problems. A total of 26 patients (21%) had postoperative hemorrhage in the resection bed. Obstructive hydrocephalus was noted in 25 (20%) patients. The entrapment of the occipital and/or temporal horns was observed in seven cases. None of the seven patients with prophylactic intraventricular stents required shunting. CONCLUSION: Although high rates of gross total or STR can be expected, the mortality and morbidity remain significant even in the modern neurosurgical era. Prophylactic intraventricular stenting in patients with large posteriorly located tumors with hydrocephalus may prevent ventricular entrapment and shunting. The main risk factors for recurrence are presence of residual disease and Ki-67 index over 5%. Recurrent symptomatic tumors should be treated surgically, whereas asymptomatic progression can be managed with stereotactic radiosurgery. Both treatment modalities are associated with low risk of complications and high tumor control rates.

Chemotherapy-induced changes in tumor consistency can allow gross total resection of previously unresectable brainstem pilocytic astrocytoma.

BACKGROUND: Low-grade gliomas (LGG) are described by the World Health Organization as Grades I and II. Among LGGs, the most common primary brain tumor is pilocytic astrocytoma (PA) and carries an excellent prognosis when treated with complete surgical resection. Cases, in which this is not possible, are associated with less favorable outcomes and worse progression-free survival. CASE DESCRIPTION: This report describes a case of a 22-year-old male, who presented with progression of a primary brainstem tumor previously treated with stereotactic radiosurgery and chemotherapy. Patient underwent surgical exploration and was diagnosed with juvenile PA, but debulking was limited by the very dense and fibrous tumor. Complete surgical resection was not possible at this time. Despite efforts to treat with chemotherapy, the patient presented a year later with clinical deterioration and severe neurologic deficits, prompting surgical re-exploration. During the second operation, the tumor was found to have undergone very significant softening in consistency, allowing for gross total resection (GTR). CONCLUSION: Aggressive treatment of brainstem LGG should be pursued whenever possible, given its generally favorable prognosis. Repeat microsurgical resection, even with a different approach, might be reasonable and safe. Finally, chemotherapy may be associated with changes in the tumor consistency that can render previously unresectable lesions amenable to successful aggressive resection.

Awake craniotomy for glioblastoma in COVID-19-positive patients and delivering the standard of care: illustrative case.

BACKGROUND: Providing the standard of care to patients with glioblastoma (GBM) during the novel coronavirus of 2019 (COVID-19) pandemic is a challenge, particularly if a patient tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Further difficulties occur in eloquent cortex tumors because awake speech mapping can theoretically aerosolize viral particles and expose staff. Moreover, microscopic neurosurgery has become difficult because the use of airborne-level personal protective equipment (PPE) crowds the space between the surgeon and the eyepiece. However, delivering substandard care will inevitably lead to disease progression and poor outcomes. OBSERVATIONS: A 60-year-old man with a left insular and frontal operculum GBM was found to be COVID-19 positive. Treatment was postponed pending a negative SARS-CoV-2 result, but in the interim, he developed intratumoral hemorrhage with progressive expressive aphasia. Because the tumor was causing dominant hemisphere language symptomatology, an awake craniotomy was the recommended surgical approach. With the use of airborne-level PPE and a surgical drape to protect the surgeon from the direction of potential aerosolization, near-total gross resection was achieved. LESSONS: Delaying the treatment of patients with GBM who test positive for COVID-19 will lead to further neurological deterioration. Optimal and timely treatment such as awake speech mapping for COVID-19-positive patients with GBM can be provided safely.

Extreme Intracranial Hypotension With Brain Herniation Treated With Repeat Bolus Intrathecal Infusions.

Intracranial hypotension (IH) is a relatively common condition associated with low cerebrospinal (CSF) pressure. The most typical symptom is orthostatic headache, although neurological deficits and changes in the level of consciousness, such as encephalopathy, stupor, and coma, may also occur. Uncomplicated CSF hypotension headaches generally resolve with rest, hydration, and analgesia. However, persistent cases may require an epidural blood patch (EBP) for resolution. Our report presents the case of a 50-year-old male with a history of intravenous (IV) drug abuse, positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) antibodies, who was admitted for new-onset headache and brain magnetic resonance imaging (MRI) findings suggesting CSF hypotension. The patient subsequently developed altered mental status with agonizing respirations, prompting intubation and admission to the intensive care unit (ICU) with neurosurgery consult. The initial exam revealed fixed and dilated pupils, suggestive of severe IH with brain herniation and the decision was made to proceed with an emergent intrathecal infusion with intraparenchymal intracranial pressure (ICP) monitoring, combined with EBP. A substantial clinical improvement was noted following the procedure. Within 45 minutes, the patient's mental status improved to normal and pupillary dilation and areflexia were no longer observed. While the procedure may need to be repeated in cases of late deterioration, this report provides evidence that intrathecal bolus saline infusion with simultaneous ICP monitoring may be considered an effective measure to treat extreme cases of IH with associated brain herniation. If performed in a timely fashion, improvement of ICP numbers, and clinical resolution can be quite rapid.

Cardiac Myxoma with Cerebral Metastases and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Case Report and Review.

Background Cardiac myxomas, the most common primary cardiac tumors, are generally benign neoplasms. Primary cardiac lymphoma is a rare cardiac malignancy with a very poor prognosis. Here we present a case of a cardiac myxoma with cerebral metastases and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) arising within the cerebral metastases. Case description A 62-year-old man, who presented with symptoms of multiple transient ischemic attacks, was found to have a left atrial myxoma. Twelve months after excision of the myxoma, the patient experienced a recurrence of neurologic symptoms. Brain magnetic resonance imaging revealed multiple hemorrhagic masses. Craniotomy was performed to resect the lesions. Histopathologic examination confirmed cardiac myxoma metastases and a small lymphocytic infiltrate within the tumor consistent with CLL/SLL. Conclusion Including the present case, there are 27 cases of cardiac myxoma cerebral metastases and 22 cases of lymphomas arising within myxomas. The present case is the first known instance of both entities in the same patient. There is no standard management for either cardiac myxoma metastases or lymphoma within a myxoma. For both diseases, surgical excision is the primary treatment modality, but postoperative chemotherapy and/or radiation have been attempted. Myxomas may create a chronic inflammatory state that could lead to the development of CLL/SLL.

Microsurgical Clip Suspension to Prevent Optic Neuropathy Following Ligation of Anterior Communicating Artery Aneurysm: A Technical Report and Surgical Video.

Anterior communicating artery (ACoA) aneurysms are among the most common intracerebral aneurysms. Complications of ACoA aneurysm include subarachnoid hemorrhage, which may occur spontaneously or as a result of trauma. While prognosis of microsurgical clip ligation is excellent, iatrogenic afferent pupillary defect secondary to mechanical compression of the optic nerve by the clips is a known complication. Our report presents a case of a 59-year-old female status post resection of a pituitary macroadenoma one year ago with a three- to four-week history of progressively worsening headache found to have a 6.5 x 5.4 mm wide neck and irregularly dysplastic aneurysmal dilation of the ACoA. During the operation, two of the longer clips appeared to be touching the optic nerve and we utilized a clip suspension technique to relieve compression. This gently elevated and suspended the two clips up to the dura, allowing for a 2 mm gap between the optic nerve and clips. This maneuver relieved mechanical compression against the optic nerve and potentially mitigated the need for surgical re-exploration in the future.

Stereotactic radiosurgical treatment of brain metastases to the choroid plexus.

PURPOSE: Choroid plexus metastases (CPM) are uncommon lesions. Consequently, optimal management of CPM is uncertain. We summarize our experience with stereotactic radiosurgery (SRS) of CPM. METHODS AND MATERIALS: Sixteen consecutive patients with presumed CPM treated with SRS between 1997 and 2007 were examined. Twelve were men with a median age at diagnosis of CPM of 61.9 ± 9.9 years; 14 had metastases from renal cell carcinoma (RCC). All patients had controlled primary disease at the time of treatment for CPM. Four patients with RCC and 1 with non-small-cell lung cancer had undergone whole-brain radiotherapy (WBRT) previously and 2 had received SRS to other brain metastases. The disease-free interval from the primary diagnosis to CPM diagnosis averaged 39.3 ± 46.2 months (range, 1.0-156.3). Five patients were asymptomatic; of the remaining 11, none had symptoms related to CPM. All presented with a single CPM. RESULTS: Average maximum diameter of the CPMs was 2.0 ± 1.0 cm (range, 0.9-4.1 cm); mean volume was 2.4 ± 2.6 cm(3) (range, 0.2-9.3). Median SRS dose was 24 Gy to the 53% isodose line (range, 14-24 Gy). Survival after SRS to the CPM was 25.3 ± 23.4 months (range, 3.2-101.6). Patients in Recursive Partitioning Analysis (RPA) class I (n = 10) had improved survival compared to those in class II (n = 6), as did those with better GPA scores. There were no local failures. After SRS, 1 patient underwent WBRT, 3 patients had one, and another had two subsequent SRS treatments to other brain lesions. Of the 14 patients who have died, 11 succumbed to systemic disease progression, 2 to progressive, multifocal central nervous system disease, and 1 to systemic disease with concurrent, stable central nervous system disease. There were no complications related to SRS. CONCLUSIONS: Most CPMs are associated with RCC. SRS represents a safe and viable treatment option as primary modality for these metastases, with excellent outcomes.

Results of a survey of neurosurgical practice patterns regarding the prophylactic use of anti-epilepsy drugs in patients with brain tumors.

INTRODUCTION: The American Association of Neurology issued guidelines discouraging the prophylactic use of anti-epilepsy drugs (AEDs) in patients with brain tumors. We surveyed neurosurgeons to evaluate practice patterns with regard to using AEDs in neurosurgical patients with brain tumors. METHODS: The survey consisted of 18 questions. Two group email blasts containing an internet link to the survey were sent to members of the American Association of Neurological Surgeons with email addresses. Uni- and multi-variate analysis of the responses was performed using t-test, Fisher's exact test, or chi-squared test, where appropriate. RESULTS: The response rate was 15.5% (386/2491). The majority of respondents (270/386; 70.0%) had more than 5 years of experience in neurosurgery. Most respondents described their practices as general (224/379; 59.1%); about one-third were members of the Joint Section on Tumors (136/381; 35.7%). More than 70% of respondents reported routine use of AED prophylaxis for patients with intra-axial gliomas or brain metastases. AED prophylaxis was also routinely used for extra-axial benign tumors or stereotactic biopsies by 53.8% and 21.4%, respectively. On multivariate analysis, the number of years in practice of ABNS certified neurosurgeons was the strongest predictor for the use of AED prophylaxis. CONCLUSIONS: Routine use of AED prophylaxis in patients with brain tumors undergoing neurosurgical procedures remains the prevailing practice pattern among members of the AANS. Additional larger prospective studies with appropriate patient stratification culminating in development of neurosurgical guidelines on AED prophylaxis in brain tumor patients is warranted.

Posterior fossa metastases: risk of leptomeningeal disease when treated with stereotactic radiosurgery compared to surgery.

INTRODUCTION: Leptomeningeal disease (LMD) represents a diffuse form of central nervous system metastatic disease that is often associated with poor quality of life and prognosis. Our objective was to compare the incidence of LMD in patients with posterior fossa metastases (PFM) following stereotactic radiosurgery (SRS) versus surgical resection. METHODS: The medical records of 93 patients aged 57.9 +/- 10.8 years (mean +/- SD) with PFM treated at the Cleveland Clinic from 1995 to 2001 were analyzed retrospectively. Treatments consisted of surgery with whole brain radiation therapy (WBRT) or SRS with or without WBRT. The impact of age, Karnofsky performance status (KPS) at presentation, Radiation Therapy Oncology Group, recursive partitioning analysis (RPA) class, status of extracranial disease, number, size, volume, pathology of brain metastases and steroid use were studied using univariate and multivariate analyses. RESULTS: There were 80 evaluable patients (10 lost to follow-up and three excluded for supratentorial surgery with subsequent LMD). LMD occurred after the surgical removal of the PFM in 9 of 18 patients (50%), whereas LMD occurred after SRS in 4 of 62 patients (6.5%) (p = 0.0028). Multivariate analysis also showed that patients who had surgery were more likely to develop LMD compared to patients treated with SRS (p = 0.0024). Patients had a median KPS decline of 30 points after LMD was diagnosed. There was no statistically significant difference in survival of patients with LMD and the rest of the patients (13.5 vs. 11.7 months, p = 0.7659). Patients treated surgically had significantly larger lesions (3.43 +/- 0.74 vs. 1.96 +/- 0.95 cm maximum diameter, p < 0.0001). All surgical patients belonged to RPA class II at diagnosis. Their survival was not different from the RPA class II patients in the SRS group. Surgery and SRS had comparable complication rates (8.1% vs. 5.6%, p = 0.99), although the surgical complications were more serious (e.g. hemorrhage, CSF leak). The duration of steroid use was longer after SRS compared to surgery (2.1 +/- 3.6 vs. 1.3 +/- 2.4 months); however, the difference was not statistically significant. Myopathy and psychosis in one patient after SRS, were the only steroid-related complications. There was no statistically significant association between the primary tumor type and the presence of LMD. CONCLUSIONS: In this retrospective analysis of patients with PFM, SRS was associated with a lower incidence of LMD than was surgery. Although LMD was associated with rapid and considerable decline in the quality of life, it did not influence the overall survival. SRS was associated with less serious complications than surgery. Surgery in this study was performed on patients with larger lesion sizes and a trend toward poorer initial performance status, which could bias these results. A prospective study directly comparing surgery and SRS and further evaluating the significance of LMD in PFM is warranted.

Metaplastic bone formation in a low grade conus glioma: case report and review of the literature.

Calcifications associated with both benign and neoplastic intra-axial lesions of the central nervous system (CNS) are well recognized. Bony metaplasia in the CNS, where there is formation of mature trabecular bone, is a much more rare entity and has not been reported in the spinal cord. We present a case of bony metaplasia in the conus medullaris associated with a low grade astrocytoma. Radiological, pathological and clinical features of this unique case are discussed.

Intraoperative imaging in glioblastoma resection.

The use of intraoperative imaging (IOI) in neurosurgical practice is proving to be yet another important advance in the evolution of brain tumor resection, particularly for the most common adult primary brain tumor--glioblastoma (GBM). The number of surgeons using IOI continues to increase, and the experience to date affords an opportunity to assess the value of the various techniques used for IOI.