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Ken Matsushima, Michihiro Kohno, and Helmut Bertalanffy

Microsurgical resection of the medullary cavernoma is rare, comprising less than 15% of more than 250 surgeries of brainstem cavernoma performed by the senior author (H.B.). This video demonstrates a case of a cavernous malformation inside the lateral part of the medulla, which was surgically treated via the olivary zone by the retrosigmoid supracondylar approach in a half-sitting position. Osseous drilling of the lateral foramen magnum provided wide exposure of the cerebellomedullary cistern around the olive., The lesion was completely dissected at the appropriate cleavage plane from the normal parenchyma. The patient developed no new neurological deficits and had no recurrence during 3 years of follow-up after the operation.

The video can be found here: https://youtu.be/7i7SccS5HmU.

Open access

Ken Matsushima, Michihiro Kohno, and Helmut Bertalanffy

Hemorrhagic brainstem cavernous malformations carry a high risk of progressive neurological deficits owing to recurrent hemorrhages and hence require complete surgical resection while minimizing damage to the dense concentration of nuclei and fibers inside the brainstem. To access lesions inside the lower pons, the senior author (H.B.) has preferred to approach the lesions via the “perifacial zone” through the pontomedullary sulcus from the inferior surface of the pontine bulge for more than 20 years., This video demonstrates a case of a cavernous malformation inside the lower pons, which was surgically treated via the pontomedullary junction through the retrosigmoid supracondylar approach in a half-sitting position. The lesion was completely removed in piecemeal fashion through a tiny incision on the sulcus, which did not cause any new neurological deficits. The modified Rankin Scale improved from 4 before the surgery to 1, and the patient had no recurrence during the 2 years of follow-up. The advantage of this access and the dissection techniques for this challenging lesion are introduced, based on our experience with more than 230 surgeries of brainstem cavernoma.

The video can be found here: https://youtu.be/0H_XqkQgQ9I.

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Uwe Spetzger, Jürgen Reul, Joachim Weis, Helmut Bertalanffy, Armin Thron, and Joachim M. Gilsbach

✓ The authors present a detailed account of the microsurgical production of bifurcation aneurysms in chinchilla rabbits for basic studies of endovascular coil embolization of aneurysms. End-to-side anastomoses of both common carotid arteries (CCAs) were performed, and a venous pouch was fitted into the newly created bifurcation. These experimental aneurysms closely mimic human cerebral aneurysms in size and hemodynamic features. Sixty-three animals underwent operation. Fifteen animals died in the course of the experiment and 15 were excluded because of a CCA occlusion within the carotid bifurcation. Electrical detachable platinum coils, also known as Guglielmi detachable coils (GDCs), and tungsten mechanical detachable coils (MDCs) were used for the endovascular occlusion of 26 bifurcation aneurysms (16 rabbits were treated with GDCs and 10 with MDCs). Initially, complete angiographic obliteration (95%–100% occlusion of the aneurysm) was achieved in nine rabbits and incomplete obliteration (< 95% occlusion) was seen in 17 animals. Final angiography 3 to 6 months later demonstrated complete occlusion in only four and partial occlusion in 22 aneurysms. At present, the histopathological examination of 17 embolized aneurysms has revealed incomplete obliteration of all aneurysms, even in those three cases that were thought to be completely embolized according to angiographic criteria. A general overestimation of the radiological degree of aneurysm obliteration was found.

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Michael Hugelshofer, Nicola Acciarri, Ulrich Sure, Dimitrios Georgiadis, Ralf W. Baumgartner, Helmut Bertalanffy, and Adrian M. Siegel

Object

Cerebral cavernous malformations (CCMs) are common vascular lesions in the brain, affecting approximately 0.5% of the population and representing 10%–20% of all cerebral vascular lesions. One-quarter of all CCMs affect pediatric patients, and CCMs are reported as one of the main causes of brain hemorrhage in this age group. Symptoms include epileptic seizures, headache, and focal neurological deficits. Patients with symptomatic CCMs can be treated either conservatively or with resection if lesions cause medically refractory epilepsy or other persistent symptoms.

Methods

The authors retrospectively analyzed 79 pediatric patients (41 boys and 38 girls) from 3 different centers, who were surgically treated for their symptomatic CCMs between 1974 and 2004. The mean age of the children at first manifestation was 9.7 years, and the mean age at operation was 11.3 years. The main goal was to compare the clinical outcomes with respect to the location of the lesion of children who preoperatively suffered from epileptic seizures.

Results

Of these patients, 77.3% were seizure free (Engel Class I) after the resection of the CCM. Significant differences in the outcome between children who harbored CCMs at different locations were not found.

Conclusions

Resection seems to be the favorable treatment of symptomatic CCMs not only in adults but also in children.

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Helmut Bertalanffy, Shinya Ichimura, Souvik Kar, Yoshihito Tsuji, and Caiquan Huang

OBJECTIVE

The aim of this study was to analyze the differences between posterolateral and posteromedial approaches to pontine cavernous malformations (PCMs) in order to verify the hypothesis that a posterolateral approach is more favorable with regard to preservation of abducens and facial nerve function.

METHODS

The authors conducted a retrospective analysis of 135 consecutive patients who underwent microsurgical resection of a PCM. The vascular lesions were first classified in a blinded fashion into 4 categories according to the possible or only reasonable surgical access route. In a second step, the lesions were assessed according to which approach was performed and different patient groups and subgroups were determined. In a third step, the modified Rankin Scale score and the rates of permanent postoperative abducens and facial nerve palsies were assessed.

RESULTS

The largest group in this series comprised 77 patients. Their pontine lesion was eligible for resection from either a posterolateral or posteromedial approach, in contrast to the remaining 3 patient groups in which the lesion location already had dictated a specific surgical approach. Fifty-four of these 77 individuals underwent surgery via a posterolateral approach and 23 via a posteromedial approach. When comparing these 2 patient subgroups, there was a statistically significant difference between postoperative rates of permanent abducens (3.7% vs 21.7%) and facial (1.9% vs 21.7%) nerve palsies. In the entire patient population, the abducens and facial nerve deficit rates were 5.9% and 5.2%, respectively, and the modified Rankin Scale score significantly decreased from 1.6 ± 1.1 preoperatively to 1.0 ± 1.1 at follow-up.

CONCLUSIONS

The authors' results suggest favoring a posterolateral over a posteromedial access route to PCMs in patients in whom a lesion is encountered that can be removed via either surgical approach. In the present series, the authors have found such a constellation in 57% of all patients. This retrospective analysis confirms their hypothesis in a large patient cohort. Additionally, the authors demonstrated that 4 types of PCMs can be distinguished by preoperatively evaluating whether only one reasonable or two alternative surgical approaches are available to access a specific lesion. The rates of postoperative sixth and seventh nerve palsies in this series are substantially lower than those in the majority of other published reports.

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Ulrich Sure, Sandra Freman, Oliver Bozinov, Ludwig Benes, Adrian M. Siegel, and Helmut Bertalanffy

Object. Cerebral cavernous malformations (CCMs) have previously been considered as congenital and biologically static malformations. On the other hand, the potential for growth and de novo generation of CCMs have also been reported. It is therefore important to study the proliferative and neoangiogenetic capacity of these lesions.

Methods. The authors studied the surgical specimens of 56 CCMs (23 deep and 33 superficial) obtained from adult patients. The proliferative activity of the endothelium and the neoangiogenetic capacity of these lesions were considered through immunohistochemical anaylsis of proliferating cell nuclear antigen (PCNA), MIB-1, Flk-1, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1α, and endoglin antibodies.

Positive immunostaining of endothelial cells occurred in 86% of patients for PCNA and in 38% of the cases for MIB-1. The expression of Flk-1 was observed in the endothelium of 71% of the cases, for VEGF in 41%, for HIF-1α in 48.1%, and for endoglin in 63.6% of the cases. The correlation of immunohistochemical and clinical data indicated that VEGF was expressed in significantly less deep-seated lesions when compared with superficial CCMs. Neither the expression of the proliferative markers nor the expression of the angiogenetic antibodies correlated with patient age at surgery, sex, or the number of recent prior hemorrhagic episodes in the patients.

Conclusions. The CCMs from adult patients are active lesions exhibiting endothelial proliferation and neoangiogenesis. According to the data in this study, neoangiogenesis is more prominent in superficial CCMs than in deep-seated CCMs and is not associated with recent prior hemorrhages.

Free access

Mario Giordano, Amir Samii, Anna C. Lawson McLean, Helmut Bertalanffy, Rudolf Fahlbusch, Madjid Samii, and Concezio Di Rocco

OBJECTIVE

The use of high-field intraoperative MRI has been largely studied for the treatment of intracranial tumors in adult patients. In this study, the authors investigated the safety, advantages, and limitations of high-field iMRI for cranial neurosurgical procedures in pediatric patients, with particular attention to craniopharyngiomas and gliomas.

METHODS

The authors performed 82 surgical procedures in patients under 16 years of age (range 0.8–15 years) over an 8-year period (2007–2014) using iMRI. The population was divided into 3 groups based on the condition treated: sellar region tumors (Group 1), gliomas (Group 2), and other pathological entities (Group 3). The patients' pre- and postoperative neurological status, the presence of residual tumor, the number of intraoperative scans, and complications were evaluated.

RESULTS

In Group 1, gross-total resection (GTR) was performed in 22 (88%) of the procedures and subtotal resection (STR) in 3 (12%). In Group 2, GTR, STR, and partial resection (PR) were performed, respectively, in 15 (56%), 7 (26%), and 5 (18%) of the procedures. In Group 3, GTR was performed in 28 (93%) and STR in 2 (7%) of the procedures. In cases of craniopharyngioma (Group 1) and glioma (Group 2) in which a complete removal was planned, iMRI allowed localization of residual lesions and attainment of the surgical goal through further resection, respectively, in 18% and 27% of the procedures. Moreover, in gliomas the resection could be extended from partial to subtotal in 50% of the cases. In 17% of the patients in Group 3, iMRI enabled the identification and further removal of tumor remnants. There was no intra- or postoperative complication related to the use of iMRI despite special technical difficulties in smaller children.

CONCLUSIONS

In this study, the use of iMRI in children proved to be safe. It was most effective in increasing the extent of tumor resection, especially in patients with low-grade gliomas and craniopharyngiomas. The most prominent disadvantage of high-field iMRI was the limitation with respect to operative positioning due to the configuration of the surgical table.

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Enlarged perivascular spaces mimicking multicystic brain tumors

Report of two cases and review of the literature

Jochen Rohlfs, Thomas Riegel, Munzir Khalil, Joanna Iwinska-Zelder, Hans-Dieter Mennel, Helmut Bertalanffy, and Dieter Hellwig

✓ The authors present two cases in which enlarged Virchow—Robin spaces were located in the basal ganglia and the thalamomesencephalic region. The incidence of such huge cystic lesions is extremely rare. The expanding nature of these lesions, demonstrated by the patients' progressive symptoms due to compression of the adjacent brain parenchyma and obstructive hydrocephalus, mimicked that of brain tumors. The two patients were successfully treated by neuroendoscopic cystocisternostomy or ventriculocystostomy. To the authors' knowledge there have been only two published reports on expanding Virchow—Robin spaces that produced a compressive effect or consequent hydrocephalus and were directly fenestrated using neuroendoscopic techniques. Neuroendoscopy appears to offer an effective surgical option in the treatment of symptomatic Virchow—Robin spaces.

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Yuan Zhu, Christian Peters, Monika Hallier-Neelsen, Dorothea Miller, Axel Pagenstecher, Helmut Bertalanffy, and Ulrich Sure

Object

Cerebral cavernous malformations (CCMs) are the most common vascular malformation of the central nervous system and involve dysregulated angiogenesis. However, the underlying mechanism of this disease is poorly understood. Phosphatase and tensin homolog (PTEN) plays a crucial role in regulating angiogenesis. The authors attempted to determine whether PTEN is involved in the pathological angiogenesis of CCM.

Methods

The authors used Western blot analysis and immunohistochemical methods to detect the expression of PTEN, PCNA, and P-Akt in the surgical specimens of CCMs and controls. The function of PTEN in cell proliferation was studied after PTEN silencing in endothelial cultures by using the short interfering RNA technique.

Results

Western blot analysis showed significant reduction of PTEN protein expression in CCMs compared with control brain tissue (p < 0.01). Immunohistochemical analysis confirmed PTEN insufficiency in 33% of vascular endothelia of CCMs, which was significantly higher than that of controls (2%, p < 0.01). Furthermore, PTEN insufficiency occurred more frequently in multiple CCMs (44%) and in small lesions (39%) than in single CCMs (28%, p < 0.05) and large lesions (30%, p < 0.05), respectively, suggesting a potential role of PTEN in the progression of the lesions. Of note, a negative correlation was observed between the expression of PTEN and PCNA in CCM endothelial cells. However, Akt was not constitutively activated in CCMs. Using cultured endothelial cells, the authors demonstrated that PTEN silencing by short interfering RNA increased Akt activation, PCNA expression, and cell proliferation (p < 0.001). Surprisingly, the PTEN silencing–mediated increase in endothelial proliferation was not reversed by the PI3K inhibitor wortmannin.

Conclusions

In this study, the authors report for the first time a significant PTEN insufficiency in CCM vessels associated with endothelial proliferation. The in vitro study provides direct evidence for a pivotal role of PTEN in regulating endothelial proliferation, most likely through a PI3K-independent pathway. The authors suggest that PTEN insufficiency is potentially involved in CCM by stimulating angiogenesis.