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Transition from meningeal melanocytoma to primary cerebral melanoma

Case report

Florian Roser, Makoto Nakamura, Almuth Brandis, Volkmar Hans, Peter Vorkapic, and Madjid Samii

✓ The authors describe the first case of an intracranial transition of a melanocytoma into a primary malignant melanoma within a short time. A 37-year-old woman presented with progressive brainstem syndrome due to a tumor, originally diagnosed and treated 12 years earlier, that extended from the petroclival area to the anterior craniocervical junction. The histological workup following subtotal tumor resection of the initial tumor had revealed the typical features of a fibrous melanocytic meningioma without increased proliferation. Ten years after the patient had completed treatment for the melanocytic meningioma, control neuroimaging demonstrated growth of the residual tumor with compression of the brainstem. Another neurosurgical intervention revealed a dark tumor of hard consistency. At this time immunohistochemical examinations demonstrated melanocytic features (expression of vimentin, S100 protein, and melan A) of the lesion with focally increased proliferation (5% of Ki-67—positive cells) but no higher mitotic activity. Clinical signs of deterioration along with imaging-confirmed tumor progression precipitated another operation within 7 months. A neuropathological examination revealed epithelial and anaplastic changes and indicated that the MIB-1 indices were greater than 25%. Pleomorphic changes and a focal high mitotic activity led to the diagnosis of a primary cerebral malignant melanoma. The patient's later clinical course consisted of a rapid diffuse meningeal spread of the lesion throughout the entire brain and spine. Despite whole-brain and stereotactic radiation therapy as well as chemotherapy, the patient died 4 months after the last neuropathological diagnosis. Although grossly resembling a meningioma, melanocytomas lack the former's histological and immunohistochemical features. The biological behavior of a melanocytoma is variable and recurrence may happen after subtotal resection, but intracranial transition into a malignant melanoma has not been observed previously.

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Volume reduction in meningiomas after gamma knife surgery

Guenther C. Feigl, Otto Bundschuh, Alireza Gharabaghi, Madjid Samii, and Gerhard A. Horstmann

Object. The purpose of this study was to evaluate the volume-reducing effects of gamma knife surgery (GKS) of meningiomas with and without previous surgical treatment.

Methods. A group of 127 patients with a mean age of 57.1 years (range 9–81 years) with 142 meningiomas (128 World Health Organization Grade I and 14 Grade II) were included in this study. The management strategy reduces tumor volume with surgery when necessary (81 patients). Stereotactic GKS with a Gamma Knife model C was performed in all tumors of suitable size. Magnetic resonance imaging follow-up examinations with volumetric tumor analysis was performed 6 months after treatment and annually thereafter.

The mean tumor volume was 5.9 cm3 (range < 5 to > 40 cm3). The mean follow-up time after GKS was 29.3 months (range 11–61 months). The mean prescription dose was 13.8 Gy (range 10–18 Gy). A reduction in volume occurred in 117 (82.4%) of all tumors, and in 20 tumors (14.1%) growth ceased. The overall tumor control rate of 96.4%. The mean volume reduction achieved with GKS was more than 46.1%. Only five tumors (3.5%) showed a volume increase.

Conclusions. Gamma knife surgery was effective in reducing meningioma volume at short-term follow up. Further studies are needed to examine the development of these findings over a longer period.

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A positron emission tomography study of cerebrovascular reserve before and after shunt surgery in patients with idiopathic chronic hydrocephalus

Petra M. Klinge, Georg Berding, Thomas Brinker, Wolfram H. Knapp, and Madjid Samii

Object

In this study the authors use positron emission tomography (PET) to investigate cerebral blood flow (CBF) and cerebrovascular reserve (CVR) in chronic hydrocephalus.

Methods

Ten patients whose mean age was 67 ± 10 years (mean ± standard deviation [SD]) were compared with 10 healthy volunteers who were 25 ±3 years of age. Global CBF and CVR were determined using 15O–H2O and PET prior to shunt placement and 7 days and 7 months thereafter. The CVR was measured using 1 g acetazolamide. Neurological status was assessed based on a score assigned according to the methods of Stein and Langfitt.

Seven months after shunt placement, five patients showed clinical improvement (Group A) and five did not (Group B). The average global CBF before shunt deployment was significantly reduced in comparison with the control group (40 ± 8 compared with 61 ± 7 ml/100 ml/minute; mean ± SD, p < 0.01). In Group A the CBF values were significantly lower than in Group B (36 ± 7 compared with 44 ± 8 ml/100 ml/minute; p < 0.05). The CVR before surgery, however, was not significantly different between groups (Group A = 43 ± 21%, Group B = 37 ± 29%). After shunt placement, there was an increase in the CVR in Group A to 52 ± 37% after 7 days and to 68 ± 47% after 7 months (p < 0.05), whereas in Group B the CVR decreased to 14 ± 18% (p < 0.05) after 7 days and returned to the preoperative level (39 ± 6%) 7 months after shunt placement.

Conclusions

The preliminary results indicate that a reduced baseline CBF before surgery does not indicate a poor prognosis. Baseline CBF before shunt placement and preoperative CVR are not predictive of clinical outcome. A decrease in the CVR early after shunt placement, however, is related to poor late clinical outcome, whereas early improvement in the CVR after shunt placement indicates a good prognosis.

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Cochlear Region of the Brainstem

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Vestibular Schwannomas: Surgical Approach

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Proliferation potential and histological features in neurofibromatosis 2-associated and sporadic meningiomas

Jussi Antinheimo, Hannu Haapasalo, Matti Haltia, Marcos Tatagiba, Sebastian Thomas, Almuth Brandis, Markku Sainio, Olli Carpen, Madjid Samii, and Juha Jääskeläinen

✓ The authors compared the histological appearance and proliferation potential of 35 meningiomas in patients with neurofibromatosis 2 (NF2) and 30 sporadic meningiomas in age- and gender-matched patients without NF2. The NF2 meningiomas showed more mitotic figures (p < 0.001) and nuclear pleomorphism (p = 0.003) than the sporadic meningiomas; however, the incidence of meningothelial, fibroblastic, and transitional subtypes occurred equally in both groups. The proliferation potential was significantly higher in the 35 meningiomas removed from 23 patients with NF2 than in the 30 sporadic meningiomas removed in the 30 patients without NF2 (mean MIB-1 labeling indices: 2.5 vs. 1.75, p = 0.0147). The higher proliferation potential of the NF2 meningiomas may reflect differences in molecular biology between sporadic and NF2 meningiomas and may be related to an earlier onset, multiplicity, and more aggressive behavior of NF2 tumors.

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Disruption of intracerebral progression of rat C6 glioblastoma by in vivo treatment with anti-CD44 monoclonal antibody

Roger Breyer, Sami Hussein, Dorel L. Radu, Klaus-Martin Pütz, Sven Gunia, Hartmut Hecker, Madjid Samii, Gerhard F. Walter, and Alexandru C. Stan

Object. Glioblastoma multiforme (GBM) invasiveness is a complex process that involves recognition and attachment of GBM cells to particular extracellular matrix (ECM) molecules before migrating into proteolytically modified matrix and inducing angiogenesis. The CD44 molecule, which is a transmembrane adhesion molecule found on a wide variety of cells including GBM, has been suggested as the principal mediator of migration and invasion. The aim of the present study was to demonstrate whether an antibody specific to the standard form of CD44 (CD44s, 85–90 kD) might prevent invasion and thus disrupt progression of C6 GBM in vivo.

Methods. Immunostaining demonstrated homogeneous expression of CD44s on the surface of C6 GBM cells and tumors. Flow cytometric analysis demonstrated binding saturation of anti-CD44s monoclonal antibody (mAb) to the receptor at 1 µg/5 × 105 cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive (up to 94 ± 2.7%; mean ± standard deviation [SD]) detachment of C6 cells from ECM-coated culture. Blocking of CD44s in vivo resulted in significantly reduced C6 brain tumors (3.6 ± 0.4% [SD])—measured as the quotient: tumor surface (mm2)/brain surface (mm2) × 100—compared with untreated (19.9 ± 0.9%) or sham-treated (19.2 ± 1.1 to 19.3 ± 2.5% [SD]) rats. Disruption of C6 GBM progression correlated with an improved food intake; treated rats were significantly less cachectic (166.6 ± 16.4 g [SD]) than those that were untreated (83 ± 2.7 g [SD]) or sham-treated (83.4 ± 1.1 to 83 ± 2.2 g [SD]) rats.

Conclusions. The authors conclude that CD44s-targeted treatment with specific mAb may represent an effective means for preventing progression of highly invasive GBMs.

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In vivo treatment with anti-CD44 monoclonal antibody disrupts intracerebral progression of C6 glioblastoma

Roger Breyer, Sami Hussein, Dorel L. Radu, Klaus-Martin Pütz, Sven Gunia, Hartmut Hecker, Madjid Samii, Gerhard F. Walter, and Alexandru C. Stan

Glioblastoma multiforme (GBM) invasiveness is a complex process that involves recognition and attachment of GBM cells to particular extracellular matrix (ECM) molecules prior to migrating into proteolytically modified matrix and inducing angiogenesis. The CD44, which is a transmembrane adhesion molecule found on a wide variety of cells including GBM, has been suggested as the principal mediator of migration and invasion. The aim of the present study was to demonstrate whether an antibody specific to the standard form of CD44 (CD44s, 85-90 kDa) might prevent invasion and thus disrupt progression of C6 GBM in vivo.

Immunostaining demonstrated homogenous expression of CD44s on the surface of C6 GBM cells and tumors. Flow cytometric analysis demonstrated binding saturation of anti-CD44s mAb to the receptor at 1 μg/5 X 105 cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive (up to 94 ± 2.7%; mean ± standard deviation [SD]) detachment of C6 cells from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in significantly reduced C6 brain tumors (3.6 ± 0.4% [SD])--measured as the quotient: tumor surface (mm2)/brain surface (mm2) X 100--as compared with untreated (19.9% ± 0.9%) or sham-treated rats (19.2 ± 1.1% to 19.3 ± 2.5% [SD]). Disruption of C6 GBM progression correlated with an improved food intake; treated rats were significantly less cachectic (166.6 ± 16.4 g [SD]) than those that were untreated (83.0 ± 2.7 g [SD]) or sham-treated (83.4 ± 1.1 g to 83.0 ± 2.2 g [SD]) rats.

The authors conclude that CD44s-targeted treatment with specific mAb may represent an effective means for preventing progression of highly invasive GBMs.

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Analysis of risk factors for venous air embolism in the semisitting position and its impact on outcome in a consecutive series of 740 patients

Shadi Al-Afif, Hesham Elkayekh, Mazin Omer, Hans E. Heissler, Dirk Scheinichen, Thomas Palmaers, Makoto Nakamura, Elvis J. Hermann, Madjid Samii, and Joachim K. Krauss

OBJECTIVE

Routine use of the semisitting position, which offers several advantages, remains a matter of debate. Venous air embolism (VAE) is a potentially serious complication associated with the semisitting position. In this study, the authors aimed to investigate the safety of the semisitting position by analyzing data over a 20-year period.

METHODS

The incidence of VAE and its perioperative management were analyzed retrospectively in a consecutive series of 740 patients who underwent surgery between 1996 and 2016. The occurrence of VAE was defined by detection of bubbles on transthoracic Doppler echocardiography (TTDE) or transesophageal echocardiography (TEE) studies, a decrease of end-tidal CO2 (ETCO2) by 4 mm Hg or more, and/or an unexplained drop in systolic arterial blood pressure (≥ 10 mm Hg). From 1996 until 2013 TTDE was used, and from 2013 on TEE was used. The possible risk factors for VAE and its impact on surgical performance were analyzed.

RESULTS

There were 404 women and 336 men with a mean age at surgery of 49 years (range 1–87 years). Surgery was performed for infratentorial lesions in 709 patients (95.8%), supratentorial lesions in 17 (2.3%), and cervical lesions in 14 (1.9%). The most frequent pathology was vestibular schwannoma. TEE had a higher sensitivity than TTDE. While TEE detected VAE in 40.5% of patients, TTDE had a detection rate of 11.8%. Overall, VAE was detected in 119 patients (16.1%) intraoperatively. In all of these patients, VAE was apparent on TTDE or TEE. Of those, 23 patients also had a decrease of ETCO2, 18 had a drop in blood pressure, and 23 had combined decreases in ETCO2 and blood pressure. VAE was detected in 24% of patients during craniotomy before opening the dura mater, in 67% during tumor resection, and in 9% during wound closure. No risk factors were identified for the occurrence of VAE. Two patients had serious complications due to VAE. Surgical performance in vestibular schwannoma surgery was not affected by the presence of VAE.

CONCLUSIONS

This study shows that the semisitting position is overall safe and that VAE can be managed effectively. Persistent morbidity is very rare. The authors suggest that the semisitting position should continue to have a place in the standard armamentarium of neurological surgery.