Effects of 5-ALA dose on resection of glioblastoma.

PURPOSE: Fluorescence-guided surgery (FGS) with the use of 5-aminolevulinic acid (5-ALA) leads to more extensive resection of high-grade glioma (HGG) and longer overall survival (OS) of patients compared to conventional resection. The purpose of this study is to investigate the effect of 5-ALA dosages on residual tumor volume (RTV) and OS in patients with glioblastoma. METHODS: A retrospective cohort study for patients who participated in a phase I and II dose-escalation clinical trial on 5-ALA for resection of HGG. A total of 25 patients were found to have newly diagnosed glioblastoma on histology and enrolled in our study. Patients receiving low doses of 5-ALA (10-30 mg/kg) (n = 6) were compared to those receiving high doses (40-50 mg/kg) (n = 19). Pre- and post-operative contrast enhanced T1W MRI were evaluated with volumetric analysis. RESULTS: Median RTV was 0.69 cm3 and 0.00 cm3 in the low and high dose groups respectively (p = 0.975). A gross total resection (GTR) was more likely in the high dose group, though this was not statistically significant. No significant difference was found in median OS between the high and low dose groups (p = 0.6787). CONCLUSIONS: High doses of 5-ALA FGS are associated with less RTV and greater probability of GTR. 5-ALA dose was not associated with OS. Further studies with a larger patient cohort are warranted.

Comparison of Using Intraoperative Computed Tomography-Based 3-Dimensional Navigation and Fluoroscopy in Anterior Cervical Diskectomy and Fusion for Cervical Spondylosis.

OBJECTIVE: Anterior cervical diskectomy and fusion (ACDF) is a highly successful procedure to treat spinal cord or nerve root compression; however, complications can still occur. With advancements in imaging, 3-dimensional (3D) reconstruction allows real-time instrument tracking in a surgical field relative to the patient's anatomy. Here, we compare plate positioning and short-term outcomes when using 3D navigation to fluoroscopy in ACDF for degenerative spine disease. METHODS: All ACDFs for cervical spondylosis performed by 6 surgeons at a single center between 2010 and 2018 were included. ACDFs were divided into those performed using 3D navigation or fluoroscopy. Records were assessed for patient demographics, American Society of Anesthesiology score, number of operated interspaces, operative time, length of stay, perioperative complications, and 90-day readmissions. Postoperative images were reviewed for lateral and angular plate deviations. RESULTS: A total of 193 ACDFs performed with 3D navigation and 728 performed with fluoroscopy were included. After controlling for demographics and surgical characteristics, using 3D navigation was associated with less lateral plate deviation (P = 0.048) and longer operative times per interspace (P < 0.001) but was not associated with angular plate deviation (P = 0.724), length of stay (P = 0.393), perioperative complications (P = 0.844), and 90-day readmissions (P = 0.539). CONCLUSIONS: Using 3D navigation in ACDF for degenerative disease is associated with slightly more midline plate positioning and comparable short-term outcomes as using fluoroscopy and can be a suitable alternative. Advantages of using this technology, such as improved visualization of anatomy, should be weighed against disadvantages, such as increased operative time, on a per-patient basis.

Use of 5-Aminolevulinic Acid for Confirmation of Lesional Biopsy Sample in Presumed High-Grade Glioma.

BACKGROUND: 5-amniolevulinic acid (5-ALA) assists neurosurgeons in defining operative margins during resection of high-grade gliomas, leading to improved rates of complete resection of enhancing tumor and progression-free survival. Here, we propose the use of 5-ALA in stereotactic biopsy for confirmation that the sample obtained is from the targeted mass. To the knowledge of the authors, this is the first known record of 5-ALA use for confirmation of pathologic specimen in stereotactic brain biopsy in the United States. This technique could be pivotal for lesions in highly eloquent areas where it is important to take as little tissue as possible in an effort to decrease neurologic deficits while still obtaining a diagnostic biopsy sample. CASE DESCRIPTION: The patient is a 67-year-old male who initially presented with computed tomography and magnetic resonance imaging concerning for a high-grade glioma in the right basal ganglia and deep white matter of the frontal lobe. Final pathology concluded that specimens obtained during biopsy were indeed pathologic at the periphery of the lesion, and there was necrotic tissue at the center of the lesion. Fluorescence of biopsy samples was 100% concordant with pathologic analysis. CONCLUSIONS: 5-ALA may prove a useful tool for intraoperative confirmation of pathologic tissue, especially in areas of high eloquence, where small biopsy sizes are essential. It may also obviate the need for an intraoperative consultation to a pathologist. However, additional studies with larger study populations are warranted.

Successful bilateral subthalamic nucleus stimulation for segmental dystonia after unilateral pallidotomy.

BACKGROUND: Several subcortical structures have been targeted for surgical treatment of dystonia, including motor thalamus, internal segment of globus pallidus (GPi), and more recently, the subthalamic nucleus (STN). Deep brain stimulation of GPi is currently the preferred surgical treatment, but it is unclear if targeting other structures would yield better results. Patients who have already had a pallidotomy yet continue to experience dystonic symptoms may be limited in further treatment options. METHODS: A patient with medically intractable, segmental, early-onset, primary torsion dystonia presented for surgical consultation after exhausting nearly all treatment options. Medications, botulinum toxin injections, cervical denervation surgery, and left-sided pallidotomy failed to give adequate relief. The patient was implanted with STN stimulating leads bilaterally according to standard procedures. RESULTS: The patient received a 36% improvement in dystonic symptoms as measured by several dystonia rating scales. These benefits persisted for 2 years after surgery despite several hardware-related complications, and the patient reported being very satisfied with the outcome. CONCLUSION: This result supports the efficacy of STN deep brain stimulation in dystonia patients, even those with prior pallidotomy.

Surgical treatments for essential tremor.

INTRODUCTION: Essential tremor is the most common form of pathologic tremor. Surgical therapies disrupt tremorogenic oscillation in the cerebellothalamocortical pathway and are capable of abolishing severe tremor that is refractory to available pharmacotherapies. Surgical methods are raspidly improving and are the subject of this review. Areas covered: A PubMed search on 18 January 2018 using the query essential tremor AND surgery produced 839 abstracts. 379 papers were selected for review of the methods, efficacy, safety and expense of stereotactic deep brain stimulation (DBS), stereotactic radiosurgery (SRS), focused ultrasound (FUS) ablation, and radiofrequency ablation of the cerebellothalamocortical pathway. Expert commentary: DBS and SRS, FUS and radiofrequency ablations are capable of reducing upper extremity tremor by more than 80% and are far more effective than any available drug. The main research questions at this time are: 1) the relative safety, efficacy, and expense of DBS, SRS, and FUS performed unilaterally and bilaterally; 2) the relative safety and efficacy of thalamic versus subthalamic targeting; 3) the relative safety and efficacy of atlas-based versus direct imaging tractography-based anatomical targeting; and 4) the need for intraoperative microelectrode recordings and macroelectrode stimulation in awake patients to identify the optimum anatomical target. Randomized controlled trials are needed.

A Phase 1 Dose-Escalation Study of Oral 5-Aminolevulinic Acid in Adult Patients Undergoing Resection of a Newly Diagnosed or Recurrent High-Grade Glioma.

BACKGROUND: The utility of oral 5-aminolevulinic acid (5-ALA)/protoporphyrin fluorescence for the resection of high-grade gliomas is well documented. This drug has received regulatory approval in Europe but awaits approval in the United States. OBJECTIVE: To identify the appropriate dose and toxicity or harms of 5-ALA used for enhanced intraoperative visualization of malignant brain tumors, reported from a single medical center in the United States. METHODS: Prior to craniotomy for resection of a presumed high-grade glioma, individuals were given oral 5-ALA as part of a rapid dose-escalation scheme. At least 3 patients were selected for each dose level from 10 to 50 mg/kg in 10 mg/kg increments. Adverse events, intensity of tumor fluorescence, and results of biopsies in areas of tumor and the tumor bed under white light and deep blue light were recorded. RESULTS: A total of 19 patients were studied in this phase 1 study. Serious adverse events were unrelated to the ingestion of 5-ALA. At the highest dose level studied (50 mg/kg), 2 out of 6 patients were observed to have transient dermatologic redness and peeling. These were grade 1 adverse events, which were not serious enough to be dose limiting. Patients at higher dose levels (>40 mg/kg) were more likely to have strong tumor fluorescence. There were no instances of false positive fluorescence. CONCLUSION: The use of 5-ALA for brain tumor fluorescence is safe and effective to a dose of 50 mg/kg. Dose-limiting toxicity was not reached in this study.

Two cases of ischemia associated with subthalamic nucleus stimulator implantation for advanced Parkinson's disease.

Deep brain stimulation is generally a safe and effective method of alleviating motor impairment in advanced-stage Parkinson's disease patients. However, adverse events of surgery have been noted, such as hemorrhage, infection, seizures, and device failure. In this report, we describe 2 cases of the unusual adverse event of ischemia associated with subthalamic nucleus stimulator implantation. We present the intraoperative neurological symptoms, microelectrode recording data, imaging findings, and other correlated events. In the first case, the clinical effects of ischemia were evident intraoperatively and coincided with silence during microelectrode recording from the ischemic region. In the second case, the timing of the ischemic event could not be determined precisely but also was associated with a difficult mapping. Subcortical ischemia may be an underrecognized event that confounds neurophysiological mapping of deep brain structures and affects clinical outcomes.

Adjuvant gamma knife stereotactic radiosurgery at the time of tumor progression potentially improves survival for patients with glioblastoma multiforme.

OBJECTIVE: Gamma knife stereotactic radiosurgery (GK-SRS) is a safe and noninvasive treatment used as adjuvant therapy for patients with glioblastoma multiforme (GBM). Several studies have yielded conflicting results in the effectiveness of radiosurgery in GBM. This study is a retrospective review of our institutional experience with GK-SRS adjuvant therapy in the treatment of GBM. METHODS: From October 1998 to January 2003, 51 consecutive patients were treated with GK-SRS as an "upfront" adjuvant therapy after surgery or at the time of tumor progression at Northwestern Memorial Hospital. Survival analysis was performed using the Kaplan-Meier actuarial method. Univariate and multivariate analyses of patient characteristics and treatment variables were performed. RESULTS: Treatment with adjuvant GK-SRS yielded a median overall survival of 14.3 months for our cohort. Survival rate of the cohort was 68% at 12 months, 30% at 24 months, and 24% at 36 months. Karnofsky performance score greater than 90 and adjuvant chemotherapy were associated with increased survival on multivariate analysis. Adjuvant GK-SRS performed at tumor progression seems to increase median survival to 16.7 months compared with 10 months when performed after the time of initial tumor resection. Median survival rates by recursive partitioning analysis class breakdown in our cohort are greater than those predicted by other studies. CONCLUSION: GK-SRS is a relatively safe and noninvasive procedure that conferred an improvement in overall survival of GBM patients in our retrospective study. Particularly, GK-SRS may improve overall survival when performed at the time of tumor progression.