Kajetan von Eckardstein

Clonal analysis in recurrent astrocytic, oligoastrocytic and oligodendroglial tumors implicates IDH1- mutation as common tumor initiating event.

Background To investigate the dynamics of inter- and intratumoral molecular alterations during tumor progression in recurrent gliomas. Methodology/Principal Findings To address intertumoral heterogeneity we investigated non- microdissected tumor tissue of 106 gliomas representing 51 recurrent tumors. To address intratumoral heterogeneity a set of 16 gliomas representing 7 tumor pairs with at least one recurrence, and 4 single mixed gliomas were investigated by microdissection of distinct oligodendroglial and astrocytic tumor components. All tumors and tumor components were analyzed for allelic loss of 1p/19q (LOH 1p/19q), for TP53- mutations and for R132 mutations in the IDH1 gene. The investigation of non- microdissected tumor tissue revealed clonality in 75% (38/51). Aberrant molecular alterations upon recurrence were detected in 25% (13/51). 64% (9/14) of these were novel and associated with tumor progression. Loss of previously detected alterations was observed in 36% (5/14). One tumor pair (1/14; 7%) was significant for both. Intratumoral clonality was detected in 57% (4/7) of the microdissected tumor pairs and in 75% (3/4) of single microdissected tumors. 43% (3/7) of tumor pairs and one single tumor (25%) revealed intratumoral heterogeneity. While intratumoral heterogeneity affected both the TP53- mutational status and the LOH1p/19q status, all tumors with intratumoral heterogeneity shared the R132 IDH1- mutation as a common feature in both their microdissected components. Conclusions/Significance The majority of recurrent gliomas are of monoclonal origin. However, the detection of divertive tumor cell clones in morphological distinct tumor components sharing IDH1- mutations as early event may provide insight into the tumorigenesis of true mixed gliomas.

Intracavitary Chemotherapy (Paclitaxel/Carboplatin Liquid Crystalline Cubic Phases) for Recurrent Glioblastoma – Clinical Observations

SummaryHuman malignant brain tumors have a poor prognosis in spite of surgery and radiation therapy. Cubic phases consist of curved biocontinuous lipid bilayers, separating two congruent networks of water channels. Used as a host for cytotoxic drugs, the gel-like matrix can easily be applied to the walls of a surgical resection cavity. For human glioblastoma recurrences, the feasibility, safety, and short-term effects of a surgical intracavitary application of paclitaxel and carboplatin encapsulated by liquid crystalline cubic phases are examined in a pilot study. A total of 12 patients with a recurrence of a glioblastoma multiforme underwent re-resection and received an intracavitary application of paclitaxel and carboplatin cubic phases in different dosages. Six of the patients received more than 15 mg paclitaxel and suffered from moderate to severe brain edema, while the remaining patients received only a total of 15 mg paclitaxel. In the latter group, brain edema was markedly reduced and dealt medically. Intracavitary chemotherapy in recurrent glioblastoma using cubic phases is feasible and safe, yet the clinical benefit remains to be examined in a clinical phase II study.

Case history: multicentric glioma with involvement of the optic chiasm

The case is reported of a man, aged 68, with a right-sided temporal glioblastoma multiform and a left sided chiasmal anaplastic glioma, as well as an occipital tumor, presumably of glial nature. The patient had a complete prostatectomy of adenocarcinoma a year before. The coincidence of multicentric gliomas and prostate cancer is briefly discussed.

The significance of intraoperative electromyographic lateral spread in predicting outcome of microvascular decompression for hemifacial spasm

OBJECTIVES During microvascular decompression (MVD) of the facial nerve for hemifacial spasm (HFS), an abnormal muscle response can be recorded upon stimulation of the facial nerve, also known as the lateral spread response. This response may vanish after MVD and has been associated with a successful outcome. The purpose of this study was to determine if resolution of lateral spread correlated with the elimination of HFS in a single surgeons experience. Design and SETTING  (1) Retrospective analysis of 38 patients undergoing MVD with intraoperative electromyography for HFS. (2) Meta-analysis of studies from the literature. MAIN OUTCOME MEASURE Presence or absence of HFS and any complications. RESULTS Lateral spread response was seen in 36 patients; 20 patients had full resolution. Of these, 15 patients became HFS free, and 5 five patients still had some degree of HFS. Sixteen patients had a persistent lateral spread response despite a technically successful MVD; 11 of these became spasm free, and 5 still suffered from some degree of facial twitching. Analyzing 16 studies reporting a total of 1301 patients, a significant correlation (p < 0.0001) between response cessation and resolution of HFS was found. CONCLUSION The role of monitoring lateral spread response as a predictor for clinical outcome is limited.

No preferential loss of paternal 19q alleles in oligodendroglial tumors

Recently, exclusive loss of paternal 19q alleles in six of six oligodendrogliomas has been reported, indicating that parental imprinting plays a role in these tumors. We examined a series of 10 oligodendrogliomas and 3 oligoastrocytomas with allelic losses on 1p and 19q for the parental origin of the lost alleles. Ten cases lost paternal 1p alleles and 3 cases lost maternal alleles. For 19q, six cases had loss of paternal alleles and seven cases of had loss of maternal alleles. These random distributions do not support the hypothesis that parental imprinting accounts for inactivation of the putative oligodendroglioma tumor suppressor genes. Ann Neurol 2003

Indocyanine green angiography in endoscopic third ventriculostomy.

BACKGROUND: Endoscopic third ventriculostomy (ETV) has become a well-established method for the treatment of noncommunicating hydrocephalus with a high success rate and a relatively low morbidity rate. However, vessel injury has been repeatedly reported, often with a fatal outcome. Vessel injury is considered to be the most threatening complication. The use of indocyanine green (ICG) angiography has become an established tool in vascular microneurosurgery. OBJECTIVE: We report our initial experience with endoscopic ICG angiography in ETV for intraoperative visualization of the basilar artery and its perforators to reduce the risk of vascular injury. METHODS: Eleven patients with noncommunicating hydrocephalus underwent ETV. Before opening of the third ventricular floor, ICG angiography was performed using a prototype neuroendoscope for intraoperative visualization of ICG fluorescence. RESULTS: In 10 patients, ETV and ICG angiography were successfully performed. In 1 case, ICG angiography failed. Even in the presence of an opaque floor of the third ventricle (n = 5), ICG angiography clearly demonstrated the course of the basilar artery and its major branches and was considered useful. CONCLUSION: ICG angiography has the potential to become a useful adjunct in ETV for better visualization of vessel structures, especially in the presence of aberrant vasculature, a nontranslucent floor of the third ventricle, or in case of reoperations. ABBREVIATIONS: ETV, endoscopic third ventriculostomy ICG, indocyanine green

Outcome After Microsurgery for Meningiomas Involving the Internal Auditory Canal

BACKGROUND:The subset of patients suffering from meningiomas truly originating in or extending into the internal auditory canal is not well described in the literature. OBJECTIVE:To evaluate postoperative facial motor and hearing outcomes in patients undergoing resection of meningiomas originating in or extending into the internal auditory canal. METHODS:Chart reviews were done of 19 consecutive patients undergoing surgery for meningiomas originating in or extending into the internal auditory canal at the Mayo Clinic, Rochester, with emphasis on clinical exam and audiometry. RESULTS:Median follow-up for the entire group was 29 months. Seventy-four percent of patients had stable facial nerve function. One patient experienced improvement. Postoperative cochlear nerve function was unchanged in 74% of patients and worsened in 21% of patients. One patient with a sudden preoperative hearing loss improved to full hearing at 3 months. CONCLUSION:Every attempt should be made to preserve hearing and facial motor function in surgical removal of posterior fossa meningiomas that originate in or extend into the internal auditory canal. Normal or nearly normal facial nerve function can be preserved in 88% of patients presenting with normal facial nerve function; serviceable hearing can be preserved in 92% of patients who present with normal hearing. A standard retrosigmoid craniotomy with drilling of the posterior canal wall of the internal auditory canal worked well in the majority of cases.

Prophylactic nimodipine treatment and improvement in hearing outcome after vestibular schwannoma surgery: a combined analysis of a randomized, multicenter, Phase III trial and its pilot study

OBJECTIVE In clinical routines, neuroprotective strategies in neurosurgical interventions are still missing. A pilot study (n = 30) and an analogously performed Phase III trial (n = 112) pointed to a beneficial effect of prophylactic nimodipine and hydroxyethyl starch (HES) in vestibular schwannoma (VS) surgery. Considering the small sample size, the data from both studies were pooled. METHODS The patients in both investigator-initiated studies were assigned to 2 groups. The treatment group (n = 70) received parenteral nimodipine (1-2 mg/hour) and HES (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 72) was not treated prophylactically. Facial and cochlear nerve functions were documented preoperatively, during the inpatient care, and 1 year after surgery. RESULTS Pooled raw data were analyzed retrospectively. Intent-to-treat analysis revealed a significantly lower risk for hearing loss (Class D) 12 months after surgery in the treatment group compared with the control group (OR 0.46, 95% CI 0.22-0.97; p = 0.04). After exclusion of patients with preoperative Class D hearing, this effect was more pronounced (OR 0.38, 95% CI 0.17-0.83; p = 0.016). Logistic regression analysis adjusted for tumor size showed a 4 times lower risk for hearing loss in the treatment group compared with the control group (OR 0.25, 95% CI 0.09-0.63; p = 0.003). Facial nerve function was not significantly improved with treatment. Apart from dose-dependent hypotension (p < 0.001), the study medication was well tolerated. CONCLUSIONS Prophylactic nimodipine is safe and may be recommended in VS surgery to preserve hearing. Prophylactic neuroprotective treatment in surgeries in which nerves are at risk seems to be a novel and promising concept. Clinical trial registration no.: DRKS 00000328 ( https://drks-neu.uniklinik-freiburg.de/drks_web/ ).

When battery exhaustion lets the lame walk: a case report on the importance of long-term stimulator monitoring in deep brain stimulation

BackgroundDeep brain stimulation is increasingly used in the treatment of advanced Parkinson’s disease. While its short-term effectiveness is well documented, there are only few reports on long-term outcomes, and the need to repeatedly reprogram the stimulator is seldom reported.Case presentationWe present a 74-year-old man with gait impairment, which had been mistaken for worsening of the disease and only remitted when the stimulator battery was exhausted indicating that the stimulator itself had been the cause.ConclusionThis case highlights the need to repeatedly monitor not only battery capacity, but also stimulator-related side-effects for an extended period after implantation and, if necessary, to refer to centres capable of systematically reprogramming the device.

Restoration of Bi-Contrast MRI Data for Intensity Uniformity with Bayesian Coring of Co-Occurrence Statistics

The reconstruction of MRI data assumes a uniform radio-frequency field. However, in practice, the radio-frequency field is inhomogeneous and leads to anatomically inconsequential intensity non-uniformities across an image. An anatomic region can be imaged with multiple contrasts reconstructed independently and be suffering from different non-uniformities. These artifacts can complicate the further automated analysis of the images. A method is presented for the joint intensity uniformity restoration of two such images. The effect of the intensity distortion on the auto-co-occurrence statistics of each image as well as on the joint-co-occurrence statistics of the two images is modeled and used for their non-stationary restoration followed by their back-projection to the images. Several constraints that ensure a stable restoration are also imposed. Moreover, the method considers the inevitable differences between the signal regions of the two images. The method has been evaluated extensively with BrainWeb phantom brain data as well as with brain anatomic data from the Human Connectome Project (HCP) and with data of Parkinson’s disease patients. The performance of the proposed method has been compared with that of the N4ITK tool. The proposed method increases tissues contrast at least 4 . 62 times more than the N4ITK tool for the BrainWeb images. The dynamic range with the N4ITK method for the same images is increased by up to +29.77%, whereas, for the proposed method, it has a corresponding limited decrease of - 1 . 15 % , as expected. The validation has demonstrated the accuracy and stability of the proposed method and hence its ability to reduce the requirements for additional calibration scans.