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Eric Suero Molina, Johannes Wölfer, Christian Ewelt, André Ehrhardt, Benjamin Brokinkel and Walter Stummer

OBJECTIVE

Fluorescence guidance with 5–aminolevulinic acid (5-ALA) helps improve resections of malignant gliomas. However, one limitation is the low intensity of blue light for background illumination. Fluorescein has recently been reintroduced into neurosurgery, and novel microscope systems are available for visualizing this fluorochrome, which highlights all perfused tissues but has limited selectivity for tumor detection. Here, the authors investigate a combination of both fluorochromes: 5-ALA for distinguishing tumor and fluorescein for providing tissue fluorescence of adjacent brain tissue.

METHODS

The authors evaluated 6 patients who harbored cerebral lesions suggestive of high-grade glioma. Patients received 5-ALA (20 mg/kg) orally 4 hours before induction of anesthesia. Low-dose fluorescein (3 mg/kg intravenous) was injected immediately after anesthesia induction. Pentero microscopes (equipped either with Yellow 560 or Blue 400 filters) were used to visualize fluorescence. To simultaneously visualize both fluorochromes, the Yellow 560 module was combined with external blue light illumination (D-light C System).

RESULTS

Fluorescein-induced fluorescence created a useful background for protoporphyrin IX (PPIX) fluorescence, which appeared orange to red, surrounded by greenly fluorescent normal brain and edematous tissue. Green brain-tissue fluorescence was helpful in augmenting background. Levels of blue illumination that were too strong obscured PPIX fluorescence. Unspecific extravasation of fluorescein was noted at resection margins, which did not interfere with PPIX fluorescence detection.

CONCLUSIONS

Dual labeling with both PPIX and fluorescein fluorescence is feasible and gives superior background information during fluorescence-guided resections. The authors believe that this technique carries potential as a next step in fluorescence-guided resections if it is completely integrated into the surgical microscope.

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Christian Ewelt, Susanne Stalder, Hans-Jakob Steiger, Gerhard Hildebrandt and Raoul Heilbronner

Object

Spinal cordectomy has recently become more important in the treatment of end-stage posttraumatic or postoperative syringomyelia and arachnopathy as a last resort to manage ascending neurological dysfunction, spasticity, and pain in paraplegic patients. The aim in this study was to confirm a clinical benefit in strict indications for cordectomy.

Methods

Between February 2000 and September 2007, 15 spinal cordectomies were performed at the Department of Neurosurgery, Cantonal Hospital, St. Gallen. Indications for treatment were end-stage myelopathies caused by syringomyelia, tethered cord syndrome, and arachnopathy with progressive spasticity and pain or progressive upper-level neurological deficits related to the tethered cord syndrome. All patients had severe motor and sensory deficits with no residual voluntary function below the affected level.

Results

Fourteen of 15 patients showed stabilization or even an improvement in motor and sensory function. Four patients suffered from progressive spasticity and 3 from deterioration due to pain. There were no other adverse surgical events.

Conclusions

Cordectomy can be a useful instrument to preserve functions of the upper extremities and to improve spasticity and pain in patients with severe myelopathy and tethered cord, syringomyelia, or arachnopathy of various etiologies.

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Eric Suero Molina, Christian Ewelt, Nils Warneke, Michael Schwake, Michael Müther, Stephanie Schipmann and Walter Stummer

OBJECTIVE

Recent efforts to improve visualization of 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PPIX) fluorescence resulted in a dual-labeling technique, combining it with fluorescein sodium in a prototype setup. Fluorescein identifies regions with blood-brain barrier breakdown in gliomas. However, normally perfused and edematous brain fluoresces unselectively, with strong background enhancement. The aim of this study was to test the feasibility of a novel, integrated filter combination using porphyrins for selective tumor identification and fluorescein for background enhancement.

METHODS

A microscope with a novel built-in filter system (YB 475) for visualizing both fluorescein and 5-ALA–induced porphyrins was used. Resection limits were identified with the conventional BLUE 400 filter system. Six patients harboring contrast ring-enhancing lesions were analyzed.

RESULTS

The complete surgical field could now be illuminated. Fluorescein was helpful for improving background visualization, and enhancing dura, edematous tissue, and cortex. Overlapping regions with both fluorophores harbored merged orange fluorescence. PPIX fluorescence was better visualized, even in areas beyond a normal working distance of approximately 25 cm, where the BLUE 400 filters recognized no or weak fluorescence.

CONCLUSIONS

The novel filter system improved general tissue brightness and background visualization, enhancing fluorescence-guided tumor resection. Furthermore, it appears promising from a scientific perspective, enabling the simultaneous and direct observation of areas with blood-brain barrier breakdown and PPIX fluorescence.

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Eric Jose Suero Molina, Thomas Niederstadt, Vincent Ruland, Gian Kayser, Walter Stummer, Christian Ewelt and Jochen Rössler

Patients with Gorham-Stout disease (GSD), a rare disease of poorly understood etiopathophysiology, suffer from progressive osteolysis. Destruction of bone matrix is caused by lymphatic vessels, which can lead to CSF leakage if parts of bony structures adjacent to CSF spaces are involved. So far, fewer than 200 patients have been reported in the literature; only 4 of these patients presented with CSF leakage. The authors report the case of a 30-year-old man with GSD and CSF leakage due to dura mater involvement after progression of an osteolytic lesion in the thoracic spine. Neurosurgical intervention, including dura repair, was needed. Experimental medical therapy with rapamycin was started, leading to disease control for more than 12 months. Progression of GSD can lead to destruction of the meninges, causing CSF leakage. The authors review 4 other cases reported in the literature and discuss therapeutic options.

Free access

Eric Suero Molina, Stephanie Schipmann, Isabelle Mueller, Johannes Wölfer, Christian Ewelt, Matthias Maas, Benjamin Brokinkel and Walter Stummer

OBJECTIVE

Awake craniotomies have become a feasible tool over time to treat brain tumors located in eloquent regions. Different techniques have been applied in neurooncology centers. Both “asleep-awake-asleep” (asleep) and “conscious sedation” were used subsequently at the authors’ neurosurgical department. Since 2013, the authors have only performed conscious sedation surgeries, predominantly using the α2-receptor agonist dexmedetomidine as the anesthetic drug. The aim of this study was to compare both mentioned techniques and evaluate the clinical use of dexmedetomidine in the setting of awake craniotomies for glioma surgery.

METHODS

The authors retrospectively analyzed patients who underwent operations either under the asleep condition using propofol-remifentanil or under conscious sedation conditions using dexmedetomidine infusions. In the asleep group patients were intubated with a laryngeal mask and extubated for the assessment period. Adverse events, as well as applied drugs with doses and frequency of usage, were recorded.

RESULTS

From 224 awake surgeries between 2009 and 2015, 180 were performed for the resection of gliomas and included in the study. In the conscious sedation group (n = 75) significantly fewer opiates (p < 0.001) and vasoactive (p < 0.001) and antihypertensive (p < 0.001) drugs were used in comparison with the asleep group (n = 105). Furthermore, the postoperative length of stay (p < 0.001) and the surgical duration (p < 0.001) were significantly lower in the conscious sedation group.

CONCLUSIONS

Use of dexmedetomidine creates excellent conditions for awake surgeries. It sedates moderately and acts as an anxiolytic. Thus, after ceasing infusion it enables quick and reliable clinical neurological assessment of patients. This might lead to reducing the amount of administered antihypertensive and vasoactive drugs as well as the length of hospitalization, while likely ensuring more rapid surgery.

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Astrid Arning, Astrid Jeibmann, Stephan Köhnemann, Benjamin Brokinkel, Christian Ewelt, Klaus Berger, Jürgen Wellmann, Ulrike Nowak-Göttl, Walter Stummer, Monika Stoll and Markus Holling

OBJECTIVE

Cerebral aneurysms (CAs) affect 2%–5% of the population, and familial predisposition plays a significant role in CA pathogenesis. Several lines of evidence suggest that genetic variations in matrix metalloproteinase genes (MMP) are involved in the etiopathology of CAs. The authors performed a case-control study to investigate the effect of 4 MMP variants from the ADAMTS family on the pathogenesis of CAs.

METHODS

To identify susceptible genetic variants, the authors investigated 8 single nucleotide polymorphisms (SNPs) in 4 genes from the ADAMTS family (ADAMTS2, -7, -12, and -13) known to be associated with vascular diseases. The study included 353 patients with CAs and 1055 healthy adults.

RESULTS

The authors found significant associations between CA susceptibility and genetic variations in 3 members of the ADAMTS family. The largest risk for CA (OR 1.32, p = 0.006) was observed in carriers of the ADAMTS2 variant rs11750568, which has been previously associated with pediatric stroke. Three SNPs under investigation are associated with a protective effect in CA pathogenesis (ADAMTS12 variant rs1364044: OR 0.65, p = 0.0001; and ADAMTS13 variants rs739469 and rs4962153: OR 0.77 and 0.63, p = 0.02 and 0.0006, respectively), while 2 other ADAMTS13 variants may confer a significant risk (rs2301612: OR 1.26, p = 0.011; rs2285489: OR 1.24, p = 0.02).

CONCLUSIONS

These results suggest that reduced integrity of the endothelial wall, as conferred by ADAMTS variants, together with inflammatory processes and defective vascular remodeling plays an important role in CA pathogenesis, although the mechanism of action remains unknown. The authors' findings may lead to specific screening of at-risk populations in the future.

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Michael Schwake, Stephanie Schipmann, Michael Müther, Louise Stögbauer, Uta Hanning, Peter B. Sporns, Christian Ewelt, Rainer Dziewas, Jens Minnerup, Markus Holling and Walter Stummer

OBJECTIVE

Decompressive craniectomies (DCs) are performed on patients suffering large cerebral infarctions. The efficacy of this procedure has been demonstrated in several trials. In some cases, however, this procedure alone is not sufficient and patients still suffer refractory elevations of intracranial pressure (ICP). The goal of this study was to determine whether resection of infarcted tissue, termed strokectomy, performed as a second-look procedure after DC, improves outcome in selected cases.

METHODS

The authors retrospectively evaluated data of patients who underwent a DC due to a cerebral infarction at their institution from 2009 to 2016, including patients who underwent a strokectomy procedure after DC. Clinical records, imaging data, outcome scores, and neurological symptoms were analyzed, and clinical outcomes and mortality rates in the strokectomy group were compared to those for similar patients in recently published randomized controlled trials.

RESULTS

Of 198 patients who underwent DC due to cerebral infarction, 12 patients underwent strokectomy as a second surgical procedure, with a median National Institutes of Health Stroke Scale (NIHSS) score of 19 for patients with versus 16 for those without secondary strokectomy (p = 0.029). Either refractory increases of ICP > 20 mm Hg or dilated pupils in addition to herniation visible on CT images were triggers for strokectomy surgery. Ten of 12 (83%) patients had infarctions in more than one territory (p < 0.001). After 12 months, 43% of patients had a good outcome according to the modified Rankin Scale (mRS) score (≤ 3). In the subgroup of patients suffering infarctions in more than one vascular territory, functional outcome after 12 months was better (mRS ≤ 3 in 40% of patients in comparison to 9%; p = 0.027). A 1:3 case-control analysis matched to age, side of infarction, sex, and vascular territory confirmed these results (mRS ≤ 3, 42% in comparison to 11%; p = 0.032). Age, NIHSS score on admission, and number of vascular territories involved were identified as risk factors in multivariate analysis (p < 0.05). Patients in the strokectomy group had more infections (p < 0.001). According to these results, the authors developed a scale (Münster Stroke Score, 0–6 points) to predict whether patients might benefit from additional strokectomy. Receiver-operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.86 (p < 0.001). The authors recommend a Münster Stroke Score of ≥ 3 as a cutoff, with a sensitivity of 92% and specificity of 66%, for predicting benefit from strokectomy.

CONCLUSIONS

In this study in comparison to former studies, mortality rates were lower and clinical outcome was comparable to that of previously published trials regarding large cerebral infarctions. Second surgery including strokectomy may help achieve better outcomes, especially in cases of infarction of more than one vascular territory.