Marcel A. Kamp

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.

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.

Altered Seizure Susceptibility in Mice Lacking the Cav2.3 E‐type Ca2+ Channel

Summary:  Purpose: Recently the Cav2.3 (E/R‐type) voltage‐gated calcium channel (VGCC) has turned out to be not only a potential target for different antiepileptic drugs (e.g., lamotrigine, topiramate) but also a crucial component in the pathogenesis of absence epilepsy, human juvenile myoclonic epilepsy (JME), and epileptiform activity in CA1 neurons. The aim of our study was to perform an electroencephalographic analysis, seizure‐susceptibility testing, and histomorphologic characterization of Cav2.3−/− mice to unravel the functional relevance of Cav2.3 in ictogenesis.

5-ALA-induced fluorescence behavior of reactive tissue changes following glioblastoma treatment with radiation and chemotherapy

BackgroundThe 5-aminolevulinic acid (5-ALA) fluorescence-guided resection of recurrent malignant glioma is a standard surgical procedure at many neuro-oncological centers and is considered to be equally reliable as the primary resection of these tumors. 5-ALA induced fluorescence (5-AIF)-guided resection has been demonstrated to be highly predictive for tumor tissue. As pseudoprogression and radiation-induced necrosis are critical differential diagnoses of glioma recurrence, the purpose of the present analysis was to analyze 5-AIF behavior in resected tissue specimens histopathologically showing regressive and reactive changes but lacking active, that is, cellular recurrent tumor tissue after adjuvant treatment of malignant glioma.MethodsA retrospective analysis was performed in patients suffering from malignant glioma who underwent surgical resection for suspected contrast-enhancing tumor recurrence (according to RANO criteria) at our institution between 2007 and 2013, but in whom histopathological analysis only revealed reactive changes. The presence of AIF in the resected tissue samples was intraoperatively assessed and classified by the surgeon, using the categories (1) no, (2) vague and (3) solid AIF.ResultsA total of 13 out of 313 patients who underwent AIF-guided surgical resection of tissue suspicious for recurrent glioma histologically demonstrated only reactive changes without active recurrent tumor tissue after adjuvant therapy. Pretreatment was chemotherapy with temozolomide in 1 patient and combined radio-/chemotherapy in 12 patients. Six patients had suffered previous tumor recurrence with a subsequently intensified adjuvant therapy. Seven of the 13 patients displayed solid, 5 patients vague and 1 patient no 5-AIF of the resected tissue specimens. However, all 5-AIF-positive lesions exhibited heterogeneous fluorescence patterns with vaguely or solidly fluorescent as well as nonfluorescent regions.ConclusionsResection of reactive tissue without active recurrent tumor after multimodal treatment for glioblastoma is frequently associated with solid or vague 5-AIF. Therefore, neurosurgeons should remain cautious when attempting to employ intraoperative 5-AIF to discriminate radiation- and chemotherapy-induced tissue changes from true disease progression. Nevertheless, 5-AIF-guided resection remains a valid tool in the neurosurgical treatment of recurrent gliomas.

Endoscopic-Assisted Visualization of 5-Aminolevulinic Acid–Induced Fluorescence in Malignant Glioma Surgery: A Technical Note

OBJECTIVE With the use of fluorescence-guided resection with 5-aminolevulinic acid (5-ALA), the rate of complete resection of the contrast-enhancing part of malignant gliomas could be increased from 36% to 65%. Because the visualization of 5-ALA-induced fluorescence depends on a sufficient exposure to fluorescent light, residual tumor tissue in deep-seated resection cavities might not be detected. In addition, subcortical parts of a large spherical tumor might not be visualized, owing to a tangential position at the periphery of the microscopic field. With the availability of a specially designed endoscope with the capability to visualize 5-ALA fluorescence, we investigated the impact of this new technique on the visualization of residual glioma tissue. METHODS A standard dose of 5-ALA 20 mg/kg was administered to 9 patients with deep-seated contrast-enhancing brain tumors 3 hours before surgery. A standard surgical exposure was performed and supplemented by the use of a specially designed endoscope with an option of 5-ALA fluorescence guidance. After microscopic visualization of the surgical cavity, endoscopic visualization was employed. If additional fluorescence tissue was detected, microscopic visualization was performed. Detected remnants of the tumor were removed and evaluated by histologic examination. RESULTS In all cases, fluorescence-guided endoscopic visualization identified 5-ALA-positive tissue not sufficiently exposed by conventional microscopic visualization. In 8 patients, histopathologic examination confirmed residual tumor tissue; in 1 patient, the endoscopic visualized tissue was classified as radiation necrosis. In this patient, the tumor was completely ALA negative microscopically. CONCLUSIONS As an additional instrument, fluorescence-guided endoscopic visualization might help to overcome technical limitations of the conventional microscopic exposure of 5-ALA-positive tumor tissue. The false-positive 5-ALA tissue indicates that endoscopic visualization may overestimate the amount of tumor, so further analyses to ascertain the sensitivity and specificity of this technique are required.

Traumatic brain injuries in illustrated literature: experience from a series of over 700 head injuries in the Asterix comic books

BackgroundThe goal of the present study was to analyze the epidemiology and specific risk factors of traumatic brain injury (TBI) in the Asterix illustrated comic books. Among the illustrated literature, TBI is a predominating injury pattern.MethodsA retrospective analysis of TBI in all 34 Asterix comic books was performed by examining the initial neurological status and signs of TBI. Clinical data were correlated to information regarding the trauma mechanism, the sociocultural background of victims and offenders, and the circumstances of the traumata, to identify specific risk factors.ResultsSeven hundred and four TBIs were identified. The majority of persons involved were adult and male. The major cause of trauma was assault (98.8%). Traumata were classified to be severe in over 50% (GCS 3–8). Different neurological deficits and signs of basal skull fractures were identified. Although over half of head-injury victims had a severe initial impairment of consciousness, no case of death or permanent neurological deficit was found. The largest group of head-injured characters was constituted by Romans (63.9%), while Gauls caused nearly 90% of the TBIs. A helmet had been worn by 70.5% of victims but had been lost in the vast majority of cases (87.7%). In 83% of cases, TBIs were caused under the influence of a doping agent called “the magic potion”.ConclusionsAlthough over half of patients had an initially severe impairment of consciousness after TBI, no permanent deficit could be found. Roman nationality, hypoglossal paresis, lost helmet, and ingestion of the magic potion were significantly correlated with severe initial impairment of consciousness (p ≤ 0.05).

Radiobiology of Radiosurgery for the Central Nervous System

According to Leksell radiosurgery is defined as “the delivery of a single, high dose of irradiation to a small and critically located intracranial volume through the intact skull.” Before its birth in the early 60s and its introduction in clinical therapeutic protocols in late the 80s dose application in radiation therapy of the brain for benign and malignant lesions was based on the administration of cumulative dose into a variable number of fractions. The rationale of dose fractionation is to lessen the risk of injury of normal tissue surrounding the target volume. Radiobiological studies of cell culture lines of malignant tumors and clinical experience with patients treated with conventional fractionated radiotherapy helped establishing this radiobiological principle. Radiosurgery provides a single high dose of radiation which translates into a specific toxic radiobiological response. Radiobiological investigations to study the effect of high dose focused radiation on the central nervous system began in late the 50s. It is well known currently that radiobiological principles applied for dose fractionation are not reproducible when single high dose of ionizing radiation is delivered. A review of the literature about radiobiology of radiosurgery for the central nervous system is presented.

Early CT Perfusion Measurement After Aneurysmal Subarachnoid Hemorrhage: A Screening Method to Predict Outcome?

OBJECTIVE The goal of the present study is to analyze the predictive impact of early CT-based perfusion measurement (CTP) on clinical outcome in patients suffering from aneurysmal SAH. METHODS Fifteen patients with aneurysmal SAH received an early CTP measurement that was performed within the first 6 h after initial bleeding. According to a specific CTP protocol, mean transit time (MTT) and time to peak (TTP) were calculated bihemispherically and correlated with the clinical initial status according to the WFNS grade as well as with the Glasgow Outcome Scale (GOS) at the time of discharge. RESULTS The MTT and TTP correlated highly significantly with the initial WFNS grade and the GOS at the time of discharge. Mean bihemispheric MTT was 3.4 s (2.8-4.1 s, SD: 0.5 s) for initially good-grade patients (WFNS° I-III) and 4.5 s (31.2-49.8 s) for poor-grade patients (WFNS° IV-V). ICP monitored in nine patients via EVD was documented within normal intracranial pressure as defined below 18 mmHg. CONCLUSION The determination of MTT and TTP using early CTP measurements in patients suffering from aneurysmal SAH demonstrated a significant correlation with the initial neurological status and the early clinical outcome.

Diversity of presynaptic calcium channels displaying different synaptic properties.

Abstract Why mediate P-/Q-type and not N-type Ca2+ channels in cerebellar inhibitory interneurons? Neurotransmitter release relies most on P-/Q- and N-type Ca2+ channels in the vast majority of neurons, although all types of voltage-gated Ca2+ channels are competent in initiating exocytosis. Up to date, it remains unclear why a particular Ca2+ channel type mediates neurotransmission in certain axon terminals and another type of Ca2+ channel evokes neurotransmission in axon terminals of another region. Therefore, the present review analyzes the diversity of presynaptic Ca2+ channels displaying different synaptic properties and focuses on an analysis of distribution and function of presynaptic voltage-gated Ca2+ channels, as well as on developmental changes.

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.