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Benjamin Brokinkel, Markus Holling, Dorothee Cäcilia Spille, Katharina Heß, Cristina Sauerland, Caroline Bleimüller, Werner Paulus, Johannes Wölfer and Walter Stummer

OBJECTIVE

The purpose of this study was to compare long-term prognosis after meningioma surgery in elderly and younger patients as well as to compare survival of elderly patients with surgically treated meningioma to survival rates for the general population.

METHODS

Five hundred meningioma patients (median follow-up 90 months) who underwent surgery between 1994 and 2009 were subdivided into “elderly” (age ≥ 65 years, n = 162) and “younger” (age < 65 years, n = 338) groups for uni- and multivariate analyses. Mortality was compared with rates for the age- and sex-matched general population.

RESULTS

The median age at diagnosis was 71 in the elderly group and 51 years in the younger group. Sex, intracranial tumor location, grade of resection, radiotherapy, and histopathological subtypes were similar in the 2 groups. High-grade (WHO Grades II and III) and spinal tumors were more common in older patients than in younger patients (15% vs 8%, p = 0.017, and 12% vs 4%, p = 0.001, respectively). The progression-free interval (PFI) was similar in the 2 groups, whereas mortality at 3 months after surgery was higher and median overall survival (OS) was shorter in older patients (7%, 191 months) than in younger patients (1%, median not reached; HR 4.9, 95% CI 2.75–8.74; p < 0.001). Otherwise, the median OS in elderly patients did not differ from the anticipated general life expectancy (HR 1.03, 95% CI 0.70–1.50; p = 0.886). Within the older patient group, PFI was lower in patients with high-grade meningiomas (HR 24.74, 95% CI 4.23–144.66; p < 0.001) and after subtotal resection (HR 10.57, 95% CI 2.23–50.05; p = 0.003). Although extent of resection was independent of perioperative mortality, the median OS was longer after gross-total resection than after subtotal resection (HR 2.7, 95% CI 1.09–6.69; p = 0.032).

CONCLUSIONS

Elderly patients with surgically treated meningioma do not suffer from impaired survival compared with the age-matched general population, and their PFI is similar to that of younger meningioma patients. These data help mitigate fears concerning surgical treatment of elderly patients in an aging society.

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Sebastian Lohmann, Tobias Brix, Julian Varghese, Nils Warneke, Michael Schwake, Eric Suero Molina, Markus Holling, Walter Stummer and Stephanie Schipmann

OBJECTIVE

Various quality indicators are currently under investigation, aiming at measuring the quality of care in neurosurgery; however, the discipline currently lacks practical scoring systems for accurately assessing risk. The aim of this study was to develop three accurate, easy-to-use risk scoring systems for nosocomial infections, reoperations, and adverse events for patients with cerebral and spinal tumors.

METHODS

The authors developed a semiautomatic registry with administrative and clinical data and included all patients with spinal or cerebral tumors treated between September 2017 and May 2019. Patients were further divided into development and validation cohorts. Multivariable logistic regression models were used to develop risk scores by assigning points based on β coefficients, and internal validation of the scores was performed.

RESULTS

In total, 1000 patients were included. An unplanned 30-day reoperation was observed in 6.8% of patients. Nosocomial infections were documented in 7.4% of cases and any adverse event in 14.5%. The risk scores comprise variables such as emergency admission, nursing care level, ECOG performance status, and inflammatory markers on admission. Three scoring systems, NoInfECT for predicting the incidence of nosocomial infections (low risk, 1.8%; intermediate risk, 8.1%; and high risk, 26.0% [p < 0.001]), LEUCut for 30-day unplanned reoperations (low risk, 2.2%; intermediate risk, 6.8%; and high risk, 13.5% [p < 0.001]), and LINC for any adverse events (low risk, 7.6%; intermediate risk, 15.7%; and high risk, 49.5% [p < 0.001]), showed satisfactory discrimination between the different outcome groups in receiver operating characteristic curve analysis (AUC ≥ 0.7).

CONCLUSIONS

The proposed risk scores allow efficient prediction of the likelihood of adverse events, to compare quality of care between different providers, and further provide guidance to surgeons on how to allocate preoperative care.

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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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Markus Holling, Astrid Jeibmann, Joachim Gerss, Bernhard R. Fischer, Hansdetlef Wassmann, Werner Paulus, Martin Hasselblatt and Friedrich K. Albert

Object

Aneurysmal subarachnoid hemorrhage (SAH) carries a severe prognosis, which is often related to the development of cerebral vasospasm. Even though several clinical and radiological predictors of vasospasm and functional outcome have been established, the prognostic value of histopathological findings remains unclear.

Methods

Histopathological findings in resected distal aneurysm walls were examined, as were the clinical and radiological factors in a series of 91 patients who had been neurosurgically treated for aneurysmal SAH. The impact of the histological, clinical, and radiological factors on the occurrence of vasospasm and functional outcome at discharge was analyzed.

Results

Histopathological findings frequently included lymphocytic infiltrates (60%), fibrosis (60%), and necrosis (50%) of the resected aneurysm wall. On univariate analysis, clinical (Hunt and Hess grade) and radiological (aneurysm size) factors as well as histopathological features—namely, lymphocytic infiltrates and necrosis of the aneurysm wall—were significantly associated with the occurrence of vasospasm. On multivariate analysis, lymphocytic infiltrates (OR 6.35, 95% CI 2.32–17.36, p = 0.0001) and aneurysm size (OR 1.22, 95% CI 1.05–1.42, p = 0.009) remained the only factors predicting the development of vasospasm. A poor functional outcome at discharge was significantly associated with vasospasm, other clinical factors (Hunt and Hess grade, alcohol consumption, hyperglycemia, and elevated white blood cell count [WBC] at admission), and radiological factors (Fisher grade and aneurysm size), as well as with histopathological features (lymphocytic infiltrates [p = 0.0001] and necrosis of the aneurysm wall [p = 0.0015]). On multivariate analysis taking into account all clinical, radiological, and histological factors; vasospasm (OR 9.82, 95% CI 1.83–52.82, p = 0.008), Hunt and Hess grade (OR 5.61, 95% CI 2.29–13.74, p = 0.0001), patient age (OR 1.09, 95% CI 1.02–1.16, p = 0.0013), elevated WBC (OR 1.29, 95% CI 1.01–1.64, p = 0.04), and Fisher grade (OR 4.35, 95% CI 1.25–15.07, p = 0.015) best predicted functional outcome at discharge.

Conclusions

The demonstration of lymphocytic infiltrates in the resected aneurysm wall is of independent prognostic value for the development of vasospasm in patients with neurosurgically treated aneurysmal SAH. Thus, histopathology might complement other clinical and radiological factors in the identification of patients at risk.

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Astrid Jeibmann, Martin Hasselblatt, Stefan Pfister, Ronald Sträter, Angela Brentrup, Markus Holling, Thomas Niederstadt, Werner Paulus and Michael C. Frühwald

The prognosis in children harboring a glioblastoma multiforme (GBM) is usually poor. Few GBMs in children, however, seem to respond quite well to adjuvant chemotherapy. The biological basis for such chemotherapy sensitivity remains uncertain. In this paper the authors report the case of a 2-month-old girl with a histologically confirmed GBM (WHO Grade IV) in whom chemotherapy was accompanied by differentiation of the malignant primary tumor into a typical gangliocytoma (WHO Grade I) showing ganglioid differentiation and expression of neuronal markers synaptophysin, neurofilament, and NeuN as well as a low Ki 67/MIB-1 proliferation index. Array-comparative genomic hybridization did not reveal genetic alterations in either specimen. Even though the underlying biological mechanisms remain to be elucidated, closer examination of frequency and prognostic significance of neuronal differentiation in pediatric GBMs within ongoing and future clinical trials may be warranted.

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Stephanie Schipmann, Michael Müther, Louise Stögbauer, Sebastian Zimmer, Benjamin Brokinkel, Markus Holling, Oliver Grauer, Eric Suero Molina, Nils Warneke and Walter Stummer

OBJECTIVE

High-grade glioma (HGG) prognosis remains dismal, with inevitable, mostly local recurrence. Regimens for improving local tumor control are therefore needed. Photodynamic therapy (PDT) using porfimer sodium has been investigated but was abandoned due to side effects and lack of survival benefits. Intracellular porphyrins induced by 5-aminolevulinic acid (5-ALA) are approved for fluorescence-guided resections (FGRs), but are also photosensitizers. Activated by light, they generate reactive oxygen species with resultant cytotoxicity. The authors present a combined approach of 5-ALA FGR and PDT.

METHODS

After 5-ALA FGR in recurrent HGG, laser diffusors were strategically positioned inside the resection cavity. PDT was applied for 60 minutes (635 nm, 200 mW/cm diffusor, for 1 hour) under continuous irrigation for maintaining optical clarity and ventilation with 100% oxygen. MRI was performed at 24 hours, 14 days, and every 3 months after surgery, including diffusion tensor imaging and apparent diffusion coefficient maps.

RESULTS

Twenty patients were treated. One surgical site infection after treatment was noted at 6 months as the only adverse event. MRI revealed cytotoxic edema along resection margins in 16 (80%) of 20 cases, mostly annular around the cavity, corresponding to prior laser diffusor locations (mean volume 3.3 cm3). Edema appeared selective for infiltrated tissue or nonresected enhancing tumor. At the 14-day follow-up, enhancement developed in former regions of edema, in some cases vanishing after 4–5 months. Median progression-free survival (PFS) was 6 months (95% CI 4.8–7.2 months).

CONCLUSIONS

Combined 5-ALA FGR and PDT provides an innovative and safe method of local tumor control resulting in promising PFS. Further prospective studies are warranted to evaluate long-term therapeutic effects.

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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.