Philipp J. Slotty

5-aminolevulinic acid (5-ALA)-induced fluorescence in intracerebral metastases: a retrospective study.

BackgroundMicrosurgical, circumferential stripping of intracerebral metastases often proves to be insufficient to prevent local tumor recurrence.ObjectiveWe were interested in the potential impact of 5-aminolevulinic acid (5-ALA)-induced-fluorescence (5-AIF) as a diagnostic tool for the resection of intracerebral metastases.MethodsA retrospective analysis was performed for 52 patients who underwent 5-AIF-guided resection for intracerebral mass lesions that histologically corresponded to metastases from tumors outside the central nervous system. The presence of ALA fluorescence in the tumor was determined in each patient. In 42 patients, fluorescence of the resection cavity after tumor removal was additionally recorded. Data were correlated with neuropathological findings in tissue specimens.ResultsA total of 32 of the 52 metastases (62%) exhibited 5-AIF in tumor parts. All 5-AIF-positive metastases exhibited an inhomogeneous fluorescence pattern. 5-AIF was neither associated with the histological type nor with the site of origin of the metastases. Residual fluorescence of the resection cavity was detected after macroscopically complete white light resection in 24 patients with 5-AIF positive metastases. Residual tumor tissue was histologically confirmed in 6 of 18 patients with available tissue specimens from such 5-AIF positive areas (33%).ConclusionsThe majority of metastases (62%) were 5-AIF positive, suggesting a potential impact of 5-AIF for improved visualization of metastatic tumor tissue within the brain. However, residual 5-AIF after macroscopically complete resection of a metastasis needs to be interpreted with caution because of the limited specificity for detection of residual tumor tissue.

A Prospective, Randomised, Double-blind, Placebo-controlled Study to Examine the Effectiveness of Burst Spinal Cord Stimulation Patterns for the Treatment of Failed Back Surgery Syndrome

Spinal cord stimulation (SCS) for the treatment of chronic pain is a well‐established therapy. However, the requirement that paresthesia be continually felt by the patient has important downsides. This study evaluated the effectiveness of a new paresthesia‐free SCS paradigm, called burst stimulation, for the treatment of failed back surgery syndrome (FBSS) with a prospective, randomized, double‐blind, placebo‐controlled design.

Microscope-integrated quantitative analysis of intraoperative indocyanine green fluorescence angiography for blood flow assessment: first experience in 30 patients.

BACKGROUND: Intraoperative measurements of cerebral blood flow are of interest during vascular neurosurgery. Near-infrared indocyanine green (ICG) fluorescence angiography was introduced for visualizing vessel patency intraoperatively. However, quantitative information has not been available. OBJECTIVE: To report our experience with a microscope with an integrated dynamic ICG fluorescence analysis system supplying semiquantitative information on blood flow. METHODS: We recorded ICG fluorescence curves of cortex and cerebral vessels using software integrated into the surgical microscope (Flow 800 software; Zeiss Pentero) in 30 patients undergoing surgery for different pathologies. The following hemodynamic parameters were assessed: maximum intensity, rise time, time to peak, time to half-maximal fluorescence, cerebral blood flow index, and transit times from arteries to cortex. RESULTS: For patients without obvious perfusion deficit, maximum fluorescence intensity was 177.7 arbitrary intensity units (AIs; 5-mg ICG bolus), mean rise time was 5.2 seconds (range, 2.9-8.2 seconds; SD, 1.3 seconds), mean time to peak was 9.4 seconds (range, 4.9-15.2 seconds; SD, 2.5 seconds), mean cerebral blood flow index was 38.6 AI/s (range, 13.5-180.6 AI/s; SD, 36.9 seconds), and mean transit time was 1.5 seconds (range, 360 milliseconds-3 seconds; SD, 0.73 seconds). For 3 patients with impaired cerebral perfusion, time to peak, rise time, and transit time between arteries and cortex were markedly prolonged (>20, >9 , and >5 seconds). In single patients, the degree of perfusion impairment could be quantified by the cerebral blood flow index ratios between normal and ischemic tissue. Transit times also reflected blood flow perturbations in arteriovenous fistulas. CONCLUSION: Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.

Modulation of migratory activity and invasiveness of human glioma spheroids following 5-aminolevulinic acid-based photodynamic treatment. Laboratory investigation.

OBJECT Five-aminolevulinic acid-mediated photodynamic therapy (ALA/PDT) can improve the clinical outcome in patients suffering from glioblastoma. Besides direct phototoxicity, additional mechanisms may contribute. Therefore, the authors studied the influence of ALA/PDT on glioblastomas migratory and invasive behavior in a human glioma cell spheroid model. METHODS Glioma spheroids were grown from human U373 and A172 cell lines. After ALA/PDT of spheroids, the authors assessed the migration of tumor cells and their capacity to invade a collagen matrix, as well as changes in their viability, morphology, and expression of matrix metalloproteinases (MMPs). RESULTS The authors found that ALA/PDT caused long-lasting, nearly complete suppression of glioma cell migration and matrix invasion compared with nontherapeutic controls, including either irradiation or incubation with ALA only. Although ALA/PDT induced tumor cell apoptosis, suppression of migration/invasion was not simply due to phototoxicity because 50% of tumor cells remained vital throughout the observation period. Moreover, the morphology of ALA/PDT-treated cells changed significantly toward a polygonal, epithelial-like appearance, which was associated with alterations in the actin cytoskeleton. Furthermore, downregulation of MMP-7 and -8 was observed after treatment whereas other MMPs remained unchanged. CONCLUSIONS In addition to directly eliminating glioma cells through apoptosis, ALA/PDT alters their invasiveness, possibly due to the effects on the cytoskeletal organization and MMP expression.

5-Aminolevulinic Acid and 18F-FET-PET as Metabolic Imaging Tools for Surgery of a Recurrent Skull Base Meningioma

Background Metabolic imaging technologies such as 5-aminolevulinic acid (ALA) fluorescence-guided resection and positron-emission tomography (PET) imaging have improved glioma surgery within the last decade. At present, these tools are not routinely used in meningioma surgery. Objective We present a case of a complex-shaped, recurrent skull base meningioma where 5-ALA fluorescence-guidance and (18)F-fluoroethyltyrosine (FET)-PET-imaging facilitated surgical resection. Material and Methods The patient underwent surgery via a combined transcranial/transnasal endoscopic approach. What was original is that both the microscope and the endoscope were equipped for 5-ALA fluorescence-guided surgery, respectively. Furthermore, preoperative FET-PET imaging was fused with computed tomography (CT) and magnetic resonance imaging (MRI) data for intraoperative navigation. The case richly illustrated the performance of the different modalities. Conclusions Metabolic imaging tools such as 5-ALA fluorescence-guided resection and navigated FET-PET were helpful for the resection of this complex-shaped, recurrent skull base meningioma. 5-ALA fluorescence was useful to dissect the adherent interface between tumor and brain. Furthermore, it helped to delineate tumor margins in the nasal cavity. FET-PET improved the assessment of bony and dural infiltration. We hypothesize that these imaging technologies may reduce recurrence rates through better visualization of tumor tissue that might be left unintentionally. This has to be verified in larger, prospective trials.

Occipital nerve stimulation for chronic migraine: A randomized trial on subthreshold stimulation

Introduction Occipital nerve stimulation (ONS) may provide pain relief in migraine patients. In this double-blinded trial we investigated the significance of paresthesia and possible placebo effects. Methods Patients already treated with ONS reporting stable treatment effect were included. “Effective stimulation,” “subthreshold stimulation” and “no stimulation” were compared. Patients cycled through all three treatment groups. Outcome was measured using the visual analog scale (VAS) for pain, McGill Pain Questionnaire and SF-36. Results Eight patients were included, mean preoperative VAS was 8.20 ± 1.22. A significant improvement in pain was observed in favor of suprathreshold stimulation compared to subthreshold stimulation (1.98 ± 1.56 vs 5.65 ± 2.11). Pain also significantly improved under subthreshold stimulation compared to no stimulation (5.65 ± 2.11 vs 8.45 ± 0.99). No changes in SF-36 were observed. Conclusions Paresthesia is not required to achieve pain reduction but suprathreshold stimulation yields better results, underlining the significance of stimulation parameter customization.

5-ALA fluorescence of cerebral metastases and its impact for the local-in-brain progression

Aim of the present study was to analyze the oncological impact of 5-ALA fluorescence of cerebral metastases. A retrospective analysis was performed for 84 patients who underwent 5-ALA fluorescence-guided surgery of a cerebral metastasis. Dichotomized fluorescence behavior was correlated to the histopathological subtype and primary site of the metastases, the degree of surgical resection on an early postoperative MRI within 72 hours after surgery, the local in-brain-progression rate and the overall survival. 34/84 metastases (40.5%) showed either strong or faint and 50 metastases (59.5%) no 5-ALA derived fluorescence. Neither the primary site of the cerebral metastases nor their subtype correlated with fluorescence behavior. The dichotomized 5-ALA fluorescence (yes vs. no) had no statistical influence on the degree of surgical resection. Local in-brain progression within or at the border of the resection cavity was observed in 26 patients (30.9%). A significant correlation between 5-ALA fluorescence and local in-brain-progression rate was observed and patients with 5-ALA-negative metastases had a significant higher risk of local recurrence compared to patients with 5-ALA positive metastases. After exclusion of the 20 patients without any form of adjuvant radiation therapy, there was a trend towards a relation of the 5-ALA behavior on the local recurrence rate and the time to local recurrence, although results did not reach significance anymore. Absence of 5-ALA-induced fluorescence may be a risk factor for local in-brain-progression but did not influence the mean overall survival. Therefore, the dichotomized 5-ALA fluorescence pattern might be an indicator for a more aggressive tumor.

Continuous perioperative apomorphine in deep brain stimulation surgery for Parkinson's disease

Abstract Background. Patients with Parkinsons disease (PD) deprived of dopaminergic medication to facilitate awake testing during the deep brain stimulation (DBS) procedure are at increased risk of neurologic deterioration.. The aim of this survey was to demonstrate the safety of subcutaneous apomorphine treatment for reducing surgery-related neurologic deterioration in patients undergoing DBS surgery for PD. Methods. Ninety-two patients who underwent DBS surgery for PD between 11/2007 and 10/2011 in our department were retrospectively analyzed for this survey. Demographic data, apomorphine dosage, side-effects and need of ICU/IMC stay were collected and analyzed. Results. Seventy-two out of 92 patients (78.3%) received apomorphine treatment; main reason for omission of treatment was intolerable nausea (16/92, 17.3%). Apomorphine treatment was well tolerated and the most common side effect was nodular panniculitis. No severe complications were observed. No patient required ICU/IMC stay related to dopaminergic deprivation. Conclusions. Perioperative withdrawal of dopaminergic medication in PD patients leads to an increased risk of neurologic and respiratory deterioration during DBS procedures. These complications can likely be tempered using perioperative subcutaneous apomorphine as a substitute. Our 5-year experience indicates a reduction in postoperative neurologic deterioration and ICU/IMC stay need. We consider perioperative apomorphine safe during DBS surgery for PD.

Preoperative localization of spinal and peripheral pathologies for surgery by computed tomography-guided placement of a specialized needle system.

OBJECTIVEExact intraoperative localization of pathologies in spinal and peripheral nerve surgery is not easily achieved. In spinal surgery, intraoperative fluoroscopy is the common method for identification of the level affected. It seldom visualizes the pathology itself and is prone to error in identifying anatomic disorders and superimposing structures. In peripheral nerve surgery, intraoperative fluoroscopy is of little value. The present technical study was conducted to evaluate the feasibility of using a preoperative computed tomography–guided needle marking system, which was previously developed for use in gynecology. The goal was to reduce intraoperative localization error and radiation exposure to patients and operating room personnel. METHODSWe used a flexible hooked-wire needle marking system, which has previously been used for preoperative marking of breast lesions, to localize and tag spinal and peripheral nerve pathologies. Marking was carried out under computed tomographic control before surgery. Seven illustrative cases were chosen for this report: 6 patients with disorders of the spine and 1 patient with a peripheral nerve schwannoma. RESULTSNo adverse reactions, aside from minor discomfort, were observed in this study. In all cases, the needle could be used as a reliable guide for the surgical approach and led directly to the pathology. In no case was additional intraoperative fluoroscopy needed. The level of radiation exposure to the patient as a result of computed tomography–based marking was similar to or less than that encountered in conventional intraoperative x-ray localization. Radiation exposure to the operating room personnel was eliminated by this method. CONCLUSIONPreoperative marking of spinal level or peripheral nerve pathologies with a flexible hooked-wire needle marking system is feasible and appears to be safe and useful for neurosurgical spinal and peripheral procedures.

An introduction to the pathophysiology of aneurysmal subarachnoid hemorrhage

Pathophysiological processes following subarachnoid hemorrhage (SAH) present survivors of the initial bleeding with a high risk of morbidity and mortality during the course of the disease. As angiographic vasospasm is strongly associated with delayed cerebral ischemia (DCI) and clinical outcome, clinical trials in the last few decades focused on prevention of these angiographic spasms. Despite all efforts, no new pharmacological agents have shown to improve patient outcome. As such, it has become clear that our understanding of the pathophysiology of SAH is incomplete and we need to reevaluate our concepts on the complex pathophysiological process following SAH. Angiographic vasospasm is probably important. However, a unifying theory for the pathophysiological changes following SAH has yet not been described. Some of these changes may be causally connected or present themselves as an epiphenomenon of an associated process. A causal connection between DCI and early brain injury (EBI) would mean that future therapies should address EBI more specifically. If the mechanisms following SAH display no causal pathophysiological connection but are rather evoked by the subarachnoid blood and its degradation production, multiple treatment strategies addressing the different pathophysiological mechanisms are required. The discrepancy between experimental and clinical SAH could be one reason for unsuccessful translational results.