Dorothea Miller

A novel platform for image-guided ultrasound.

OBJECTIVE:The combination of classic neuronavigation and intraoperative ultrasound is a recent innovation in image guidance technology. However, this technique requires two hardware components (neuronavigation and an ultrasound system). It was the aim of the study to describe a new simplified technology of a so-called one-platform navigation system developed by our institution in collaboration with the industry and to demonstrate its range of various applications. METHODS:An ultrasound device (IGSonic; BrainLAB, Munich, Germany) is integrated into the VectorVision2 navigation system (BrainLAB, Munich, Germany). The IGSonic Probe 10V5 is connected to the VectorVision Navigation station via an IGSonic Device Box. Once the ultrasound probe is calibrated, the navigated ultrasound displays the sonographic image of the intracranial anatomy on the navigation screen in a composed overlay fashion. It might depict vascular structures within the ultrasound plane by a duplex mode. Ultrasound can also be operated independently from navigation. RESULTS:The VectorVision2 system combines intraoperative ultrasound data sets with preoperatively acquired neuronavigation data sets in plug and play fashion. The system provides a cost-effective intraoperative imaging modality that offers a good anatomic orientation by various composite images, including the display of the amount of brain shift. In our institution, the comprehensible interface led to a routine use of the technology by several neurosurgeons who had not been familiar with the ultrasound technology before. CONCLUSION:The integration of an ultrasound device into an existing navigation system has been successfully developed. The system offers a friendly user interface and cost-effective intraoperative imaging feedback. Although brain shift can be visualized by an image overlay technology as demonstrated by the present system, future developments should aim at fusion techniques of both intra- and preoperative image data sets.

Differential angiogenesis function of CCM2 and CCM3 in cerebral cavernous malformations

OBJECT Loss-of-function mutations in CCM genes are frequently detected in familial cerebral cavernous malformations (CCMs). However, the current functional studies of the CCM genes in vitro have been performed mostly in commercially purchased normal cell lines and the results appeared discrepant. The fact that the cerebral vascular defects are rarely observed in CCM gene-deficient animals suggests the requirement of additional pathological background for the formation of vascular lesions. Consistent with these data, the authors assumed that silencing CCM genes in the endothelium derived from CCMs (CCM-ECs) serves as a unique and valuable model for investigating the function of the CCM genes in the pathogenesis of CCMs. To this end, the authors investigated the role and signaling of CCM2 and CCM3 in the key steps of angiogenesis using CCM-ECs. METHODS Endothelial cells (ECs) derived from CCMs were isolated, purified, and cultured from the fresh operative specimens of sporadic CCMs (31 cases). The CCM2 and CCM3 genes were silenced by the specific short interfering RNAs in CCM-ECs and in control cultures (human brain microvascular ECs and human umbilical vein ECs). The efficiency of gene silencing was proven by real-time reverse transcriptase polymerase chain reaction. Cell proliferation and apoptosis, migration, tube formation, and the expression of phosphor-p38, phosphor-Akt, and phosphor-extracellular signal-regulated kinase-1 and 2 (ERK1/2) were analyzed under CCM2 and CCM3 silenced conditions in CCM-ECs. RESULTS The CCM3 silencing significantly promoted proliferation and reduced apoptosis in all 3 types of endothelium, but accelerated cell migration exclusively in CCM-ECs. Interestingly, CCM2 siRNA influenced neither cell proliferation nor migration. Silencing of CCM3, and to a lesser extent CCM2, stimulated the growth and extension of sprouts selectively in CCM-ECs. Loss of CCM2 or CCM3 did not significantly influence the formation of the tubelike structure. However, the maintenance of tube stability was largely impaired by CCM2, but not CCM3, silencing. Western blot analysis revealed that CCM2 and CCM3 silencing commonly activated p38, Akt, and ERK1/2 in CCM-ECs. CONCLUSIONS The unique response of CCM-ECs to CCM2 or CCM3 siRNA indicates that silencing CCM genes in CCM-ECs is valuable for further studies on the pathogenesis of CCMs. Using this model system, the authors demonstrate a distinct role of CCM2 and CCM3 in modulating the different processes of angiogenesis. The stimulation of endothelial proliferation, migration, and massively growing and branching angiogenic sprouts after CCM3 silencing may potentially contribute to the formation of enriched capillary-like immature vessels in CCM lesions. The severe impairment of the tube integrity by CCM2, but not CCM3, silencing is associated with the different intracranial hemorrhage rate observed from CCM2 and CCM3 mutation carriers. The activation of p38, ERK1/2, and Akt signal proteins in CCM2- or CCM3-silenced CCM-ECs suggests a possible involvement of these common pathways in the pathogenesis of CCMs. However, the specific signaling mediating the distinct function of CCM genes in the pathogenesis of CCMs needs to be further elucidated.

Intraoperative ultrasound assistance in treatment of intradural spinal tumours

OBJECTIVE Currently, the standard practice to treat intradural spinal tumours involves microsurgical resection of the lesions. It is essential to be able to locate the lesion precisely to reduce the risk of neurological morbidity. The purpose of this study was to evaluate intraoperative ultrasonography (IOUS) in visualizing intradural spinal tumours, and assess its potential to improve surgical precision and minimize surgical trauma. METHODS Between January 2006 and July 2007, 30 patients with suspected intradural spinal tumours underwent surgery with the aid of IOUS. There were 13 patients with intramedullary tumours (ependymoma=2, astrocytoma=5, hemangioblastoma=2 and metastasis=4); and 14 patients with extramedullary tumours (meningioma=6, neurinoma=6, filum terminale ependymoma=1 and lipoma=1). In 3 patients histopathology did not reveal any neoplasm despite an MRI suggesting tumour. Their sonographic features are analyzed and the advantages of IOUS are discussed. RESULTS The shape and expansion of intradural tumours could be visualized on IOUS. The sonographic visualization allowed adapting the approach to an appropriate location and size before dura opening. Certain sonographic features can be used for a differential diagnosis of different intradural tumours. In addition, IOUS can inform neurosurgeons about the location of the neoplastic tissue, its relation to the spinal cord and the size of residual tumour following excision. CONCLUSIONS IOUS is a sensitive intraoperative tool. When appropriately applied to assist surgical procedures, it offers additional intraoperative information that helps to improve surgical precision and therefore might reduce the procedure related morbidity.

Transsulcal approach supported by navigation-guided neurophysiological monitoring for resection of paracentral cavernomas.

OBJECTIVES The aim of the study is to evaluate tools that can improve surgical precision and minimize surgical trauma for removal of cavernomas in the paracentral area. Moreover, the surgical strategies for the treatment of symptomatic epilepsy in cavernoma patients are discussed. PATIENTS AND METHODS Between June 2000 and July 2007, 17 patients suffering from paracentral cavernoma underwent surgery via a transsulcal approach with the aid of neuronavigation, functional mapping and neurophysiological intraoperative monitoring. To optimize outcome for procedures in the paracentral area, the hemosiderin-stained tissue was removed entirely except for a small proportion on the side of precentral gyrus. RESULTS All cavernomas and their adjacent sulci could be precisely located with the aid of ultrasonography-assisted neuronavigation. By combining preoperative fMRI and intraoperative neurophysiological monitoring, including SEP, MEP and cortical mapping, the motor cortex could be defined in all cases. Thus damage to the primary motor area could be avoided during resection of cavernomas. All the lesions located in the paracentral area were removed completely via transsulcal microsurgical approach without neurological deficits. No significant seizures were induced during surgery. CONCLUSIONS The successful excision of these lesions was effected by the following four key factors: (1) the precise location of the lesion supported by intraoperative neuronavigation; (2) the preservation of the eloquent area with the aid of functional mapping; (3) a minimally invasive transsulcal microsurgical approach; and (4) the entire removal of cavernoma and hemosiderin-stained tissue.

Epileptogenicity of cavernomas depends on (archi-) cortical localization.

BACKGROUND:Patients with cerebral cavernomas have an estimated risk of the development of epilepsy of 1.5% to 2.4% per patient-year. OBJECTIVE:To clarify the predictive value of different risk factors for epilepsy in patients with supratentorial cavernomas. METHODS:We retrospectively analyzed data of 109 patients with supratentorial cavernomas. The correlation of epilepsy with the variables of single or multiple cavernomas, sex, age, side, cortical involvement, mesiotemporal archicortical vs neocortical involvement, lobar location of neocortical cavernomas, the presence of a hemosiderin rim and of edema, and the maximal diameters of cavernoma, hemosiderin rim, and edema, if present, were calculated using univariate and multivariate penalized likelihood logistic regression models. RESULTS:Cortical involvement was the most relevant risk factor for epilepsy (P < .0001). No patient with a subcortical cavernoma presented with epilepsy. Epilepsy was more common in patients with mesiotemporal archicortical cavernomas than in patients with neocortical cavernomas (P = .02), whereas the lobar location of neocortical cavernomas was not significantly associated with the risk of the development of epilepsy. In the multivariate analysis, a greater diameter of the cavernoma, the absence of edema, and localization in the left hemisphere were also associated with the occurrence of epilepsy (P < .05). CONCLUSION:The epileptogenicity of supratentorial cavernomas depends on cortical, especially mesiotemporal archicortical, involvement. Exclusively subcortical cavernomas are highly unlikely to cause epilepsy. This information is helpful in counseling patients with cavernomas regarding their risk of epileptic seizures and in patients with multiple cavernomas and epilepsy to generate a valid hypothesis of which cavernoma may cause epilepsy.

The role of underlying structural cause for epilepsy classification: Clinical features and prognosis in mesial temporal lobe epilepsy caused by hippocampal sclerosis versus cavernoma

Purpose:  The recent “Report of the ILAE Commission on Classification and Terminology” recommends an epilepsy classification that gives more emphasis to the underlying structural or metabolic cause rather than to the localization of the epileptogenic zone. The aim of the present study was to investigate differences in clinical features, treatment response, and prognosis in patients with mesial temporal lobe epilepsy (MTLE) caused by hippocampal sclerosis (MTLE‐HS) or singular mesiotemporal cavernomas (MTLE‐C) in order to evaluate the impact of underlying pathology on the course of the disease while controlling for localization.

Intraoperative Ultrasound to Define Focal Cortical Dysplasia in Epilepsy Surgery

Focal cortical dyplasia (FCD) is a frequent cause of medication‐resistant focal epilepsy. Patients with FCD may benefit from epilepsy surgery. However, it is difficult to intraoperatively define lesion boundaries. In this case report we present a novel tool to identify FCD intraoperatively. A patient with frontal lobe epilepsy underwent resection of a left frontomesial FCD. Image guidance was achieved by intraoperative ultrasound, which depicted the lesion with a higher resolution than preoperative MRI. Postoperatively the patient remained seizure free. Intraoperative ultrasound may be helpful in identifying and targeting subtle epileptogenic lesions, which are difficult to visualize.

Candidate genes for the progression of malignant gliomas identified by microarray analysis

Malignant astrocytomas of World Health Organization (WHO) grade III or IV have a reduced median survival time, and possible pathways have been described for the progression of anaplastic astrocytomas and glioblastomas, but the molecular basis of malignant astrocytoma progression is still poorly understood. Microarray analysis provides the chance to accelerate studies by comparison of the expression of thousands of genes in these tumours and consequently identify targeting genes. We compared the transcriptional profile of 4,608 genes in tumours of 15 patients including 6 anaplastic astrocytomas (WHO grade III) and 9 glioblastomas (WHO grade IV) using microarray analysis. The microarray data were corroborated by real-time reverse transcription-polymerase chain reaction analysis of two selected genes. We identified 166 gene alterations with a fold change of 2 and higher whose mRNA levels differed (absolute value of the t statistic of 1.96) between the two malignant glioma groups. Further analyses confirmed same transcription directions for Olig2 and IL-13Rα2 in anaplastic astrocytomas as compared to glioblastomas. Microarray analyses with a close binary question reveal numerous interesting candidate genes, which need further histochemical testing after selection for confirmation. IL-13Rα2 and Olig2 have been identified and confirmed to be interesting candidate genes whose differential expression likely plays a role in malignant progression of astrocytomas.

The benefit of image guidance for the contralateral interhemispheric approach to the lateral ventricle

OBJECTIVES Recently, neurosurgeons have increasingly faced small intracerebral lesions in asymptomatic or minimally symptomatic patients. Here, we evaluated a series of four patients with nearly asymptomatic intraventricular tumors close to the corpus callosum that had been treated with the aid of an image-guided transcallosal approach. PATIENTS AND METHODS Four consecutive patients suffering from left intra- and paraventricular tumors were operated on via a contralateral interhemispheric transcallosal approach with the aid of neuronavigation. Our image-guided system directed: (1) the skin incision, (2) the interhemispheric dissection, and (3) the incision of the corpus callosum. RESULTS Using the image-guided contralateral interhemispheric transcallosal approach to the left ventricle all lesions have been completely resected without the risk of damage to the dominant hemisphere. The callosal incision was kept as limited as possible (1.2-2.1cm) depending on the size of the tumor. No postoperative neurological or neuropsychological deficit was observed in our series. CONCLUSION Neuronavigation facilitates a safe and targeted contralateral interhemispheric transcallosal approach to the dominant hemispheres lateral ventricle. Our technique minimizes the risk of damage to the dominant hemisphere and requires only a limited opening of the corpus callosum, which might decrease the risk of neuropsychological morbidity.

Stand-alone 3D-ultrasound navigation after failure of conventional image guidance for deep-seated lesions

Image guidance has proven to be an important tool in surgery for deep-seated or eloquently located cavernomas. However, neuronavigation depending on preoperative images can fail. Thus, the displayed anatomy might be distorted already during the approach. This report demonstrates the use of three-dimensional intraoperative ultrasound (3D-US) as a rescue tool, when conventional navigation is erroneous. Two patients with symptomatic cavernomas, the one located subcortically in the right peritrigonum, the other in the left thalamus, were operated in our clinic via an image-guided approach. An integrated ultrasound-navigation system was used for neuronavigation. In both cases, navigation based on preoperative MRI failed after the craniotomy because patient-to-image registration was lost. In both cases, a simple registration of the patient’s orientation was performed. Then a 3D-US volume was acquired and navigation was performed using the 3D-US data set. This is accurate as image acquisition and navigation are done in the same system. The cavernoma was visualized without difficulties in both cases. It could be reached directly via the ultrasound-guided approach. Patients’ symptoms improved postoperatively and a complete resection could be documented. Two cavernomas were successfully resected using 3D-US guidance. In our experience, stand-alone 3D-US navigation is an effective option if conventional MRI-based navigation fails.