Rainer Ritz

Do antibiotic-impregnated shunts in hydrocephalus therapy reduce the risk of infection? An observational study in 258 patients

BackgroundShunt infection in hydrocephalus patients is a severe, even life-threatening complication. Antibiotic-impregnated shunts (AIS) have been developed in an attempt to reduce rate of shunt infection. The study was performed to analyze if AIS can diminish the rate of shunt infection. The pathogenic nature of shunt infection in patients with AIS systems and those without antibiotic impregnated shunts (non-AIS) was compared.MethodsOver a period of 24 months in the Department of Neurosurgery at University Hospital of Tübingen shunt surgery was performed in 258 patients. In 86 patients AIS systems were implanted. Shunt catheters were commercially impregnated with clindamycin and rifampicin. Analysis of the clinical data included sex, age, classification of hydrocephalus, shunt types and risk factors for shunt infection [age (< 1 year and > 80 years), prematurely born patients, external ventricular drainage, former shunt infection, former systemic infection, disturbance of consciousness, former radiation-/chemotherapy]. Infection rates and underlying bacterial pathogens of patients with AIS were compared to patients with implanted non-AIS systems (172 patients).ResultsAIS and non-AIS patients did not differ in sex, etiology of hydrocephalus and the shunt type. In the AIS group 72 out of 86 patients had at least one risk factor (83.7 %), compared to 126 patients in the non-AIS group (73.3 %). There was no significant difference between the two groups (p = 0.0629; Fishers exact test). In patients with no risk factors, only one patient with non-AIS suffered from shunt infection. In patients with one or more risk factors the rate for shunt infection was 7.14 % in patients with non-AIS and 6.94 % in patients with AIS. Former shunt infection (p = 0.0124) was related to higher risk for shunt infection. The use of AIS had therefore no significant advantage (p = 0.8611; multiple logistic regression).Significantly related to a shunt infection was the number of shunt surgeries. 190 interventions in the AIS group (2.21 interventions per patient) and 408 in the non-AIS group (2.37 interventions per patient) had been performed (p = 0.3063; Wilcoxon). There was no shunt infection in the group of patients on whom only one shunt surgery was performed. In patients with at least two shunt surgeries the infection rate was 9%. The infection rate in AIS patients was 5/52 (9.6 %) and in the non-AIS 10/114 (8.77 %), (p = 1.0; Fishers exact test). Staphylococcus epidermidis was the most frequent pathogen for shunt infection. Fourteen out of 15 infections occurred within the first 6 months of surgery. The most frequent pathogen for shunt infection was S. epidermidis. No toxic or allergic complications were seen using the AIS shunt systems. The presented data show a remarkably low infection rate of 5.8 % in the non-AIS group compared to other studies which demonstrated a significant decrease in the infection rate by AIS.ConclusionAIS did not significantly reduce shunt infection in hydrocephalus patients in the presented study. In the AIS group three patients suffered from shunt infections caused by skin ulceration or neurosurgical procedures with exposure of the cerebrospinal liquor after shunt implantation. AIS was not developed to prevent infection in such cases, therefore an advantage of AIS can not be excluded. In view of the presented data and the small number of reported studies a prospective randomized multicenter study is required.

Distinguishing recurrent high-grade gliomas from radiation injury: a pilot study using dynamic contrast-enhanced MR imaging.

RATIONALE AND OBJECTIVES The accurate delineation of tumor recurrence and its differentiation from radiation injury in the follow-up of adjuvantly treated high-grade gliomas presents a significant problem in neuro-oncology. The aim of this study was to investigate whether hemodynamic parameters derived from dynamic contrast-enhanced (DCE) T1-weighted magnetic resonance imaging (MRI) can be used to distinguish recurrent gliomas from radiation necrosis. MATERIALS AND METHODS Eighteen patients who were being treated for glial neoplasms underwent prospectively conventional and DCE-MRI using a 3T scanner. The pharmacokinetic modelling was based on a two-compartment model that allows for the calculation of K(trans) (transfer constant between intra- and extravascular, extracellular space), v(e) (extravascular, extracellular space), k(ep) (transfer constant from the extracellular, extravascular space into the plasma), and iAUC (initial area under the signal intensity-time curve). Regions of interest (ROIs) were drawn around the entire recurrence-suspected contrast-enhanced region. A definitive diagnosis was established at subsequent surgical resection or clinicoradiologic follow-up. The hemodynamic parameters in the contralateral normal white matter, the radiation injury sites, and the tumor recurrent lesions were compared using nonparametric tests. RESULTS The K(trans), v(e), k(ep), and iAUC values in the normal white matter were significantly different than those in the radiation necrosis and recurrent gliomas (0.01, <P < .0001). The only significantly different hemodynamic parameter between the recurrent tumor lesions and the radiation-induced necrotic sites were K(trans) and iAUC, which were significantly higher in the recurrent glioma group than in the radiation necrosis group (P ≤ .0184). A K(trans) cutoff value higher than 0.19 showed 100% sensitivity and 83% specificity for detecting the recurrent gliomas, whereas an iAUC cutoff value higher than 15.35 had 71% sensitivity and 71% specificity. The v(e) and k(ep) values in recurrent tumors were not significantly higher than those in radiation-induced necrotic lesions. CONCLUSIONS These findings suggest that DCE-MRI may be used to distinguish between recurrent gliomas and radiation injury and thus, assist in follow-up patient management strategy.

Neurosurgical Procedures in the Semisitting Position: Evaluation of the Risk of Paradoxical Venous Air Embolism in Patients with a Patent Foramen Ovale

OBJECTIVE To analyze the actual risk for patients with a patent foramen ovale (PFO) to experience a clinically relevant venous air embolism (VAE) during surgery performed in the semisitting position. METHODS All procedures were performed between January 2008 and December 2009, under general anesthesia and in the semisitting position. Transesophageal echocardiography (TEE) and capnometry were used intraoperatively to monitor for air bubbles in the venous system. RESULTS Of 200 consecutive patients who all were operated on in the semisitting position, 52 patients (26%) had a diagnosis of PFO. Rates of VAE in patients were graded as follows: grade 0 (no air bubbles visible, no air embolism), 23 patients (44.2%); grade I (air bubbles on TEE), 22 patients (42.3%); grade II (air bubbles on TEE with decrease of end-tidal carbon dioxide [ETCO2] ≤ 3 mm Hg), 2 patients (3.8%); grade III, air bubbles on TEE with decrease of ETCO2 >3 mm Hg, 4 patients (7.7%); grade IV, air bubbles on TEE with decrease of ETCO2 >3 mm Hg and decrease of mean arterial pressure ≥ 20% or increase of heart rate ≥ 40% (or both), 1 patient (1.9%); and grade V, VAE causing arrhythmia with hemodynamic instability requiring cardiopulmonary resuscitation, 0 patients (0%). There were no deaths in this series, and no new or unexplained, mild or severe neurologic deficits were caused by a VAE. CONCLUSIONS Under standardized anesthesia and neurosurgical protocols, patients with a PFO can be operated on safely in the semisitting position.

Dynamics of expression patterns of AQP4, dystroglycan, agrin and matrix metalloproteinases in human glioblastoma

In human glioblastoma, the blood–brain barrier (BBB) is disturbed. According to our concept, the glio-vascular relationships and thus the control of the BBB are essentially dependent on the polarity of astroglial cells. This polarity is characterized by the uneven distribution of the water channel protein aquaporin-4 (AQP4), dystroglycan and other molecules. Recently, we were able to show that the extracellular matrix component agrin is important for the construction and localization of the so-called orthogonal arrays of particles (OAPs), which consist in AQP4. Here, combining freeze-fracture electron microscopy, immunohistochemistry and Western blotting, we describe alterations of expression and distribution of AQP4, dystroglycan, agrin and the matrix metalloproteinases (MMP) 2, 3 and 9 in human primary glioblastomas (eight primary tumours, six recurrent tumours). Increase of MMP3- and MMP2/9 immunoreactivities went along with loss of agrin and dystroglycan respectively. On the protein level, AQP4 expression was increased in glioblastoma compared to control tissue. This was not accompanied by an increase of OAPs, suggesting that AQP4 can also occur without forming OAPs. The results underline our concept of the loss of glioma cell polarity as one of the factors responsible for the disturbance of the neurovascular unit and as an explanation for the formation of edemas in the glioblastoma.

Management of skull based meningiomas in the elderly patient

BACKGROUND The demographic evolution of Western society together with availability of modern imaging techniques leads to an increasing diagnosis of meningioma patients over 70 years of age. This raises the question of appropriate management of this histologically benign tumour in a geriatric population. DESIGN Forty-three patients aged over 70 years were analyzed and matched in a retrospective study with a younger group of 89 patients according to tumour size, histology, symptoms, recurrence and presence of neurofibromatosis II. RESULTS Changes in postoperative Karnofsky scores were not statistically different between the two age groups. Neurological outcome was worse among the younger group (12% vs. 7% deterioration). Regarding surgical complications we noted only a statistically significant higher infection rate in the geriatric age group. There was no peri-operative mortality. CONCLUSIONS Age alone is not a criterion to deny a priori skull base surgery, since well selected geriatric patients may benefit from a meningioma operation that may enhance future quality of life.

Specific intensity imaging for glioblastoma and neural cell cultures with 5-aminolevulinic acid-derived protoporphyrin IX

The fluorescence of protophorphyrin IX (PpIX) synthesized after incubation with 5-aminolevulinic acid (5-Ala) is used for the intraoperative visualisation of glioma cells in vivo. Such fluorescence may also be useful for the photodynamic therapy (PTD) of gliomas. A significant difference of fluorescence intensity in tumor cells compared to neurons is required for this application. To explore this, eight human glioma cell lines (LN-18, LN-428, U87MG, U373MG, D247MG, U251MG, LN-308, T98G) were compared with human astrocytes (SV-FHAS) and rat neurons after incubation for different periods of timein vitro with 5-Ala (1mg/ml). Fluorescence intensity profiles were measured by a digital camera comparing glioma cell lines with control cells. All glioma cell lines could be discriminated from neural cells by their intensity of fluorescence by post-hoc tests for pairwise comparisons using Tukey’s honestly significant difference test, at the global significance level of 5%. The glioma cell lines showed significant variation in this possibly limiting clinical use of fluorescence as a guide for resection.

Low grade ganglioglioma rapidly progressing to a WHO grade IV tumor showing malignant transformation in both astroglial and neuronal cell components

Gangliogliomas are rare CNS neoplasms mostly occuring in young adults and are usually assigned to WHO grade I. The few cases of WHO grade IV gangliogliomas were either primarily malignant glio‐neuronal tumors or underwent malignant progression from other WHO grades after radiotherapy. Herein, we present the case of a now 47‐year‐old female patient presenting with a benign ganglioglioma and showing a tumor recurrence 2 years later with an anaplastic ganglioglioma, assigned to WHO grade IV, with malignant transformation in both glial and neuronal components. The presented case is the first reported low‐grade ganglioglioma rapidly progressing to a WHO grade IV glio‐neuronal tumor not being associated with radiotherapy and showing malignant transformation in both astroglial and neuronal tumor cell components.

Hypericin for visualization of high grade gliomas: First clinical experience

AIMS We aimed to demonstrate that Hypericin, a component of St. Johns Wort, selectively visualizes malignant gliomas. Hypericin is known as one of the most powerful photosensitizers in nature with excellent fluorescent properties. METHODS In five patients with a recurrence of a malignant glioma a newly developed water soluble formulation of hypericin was given intravenously (0.1 mg/kg body weight) 6 h before the surgical procedure. Tumor resection was performed under white light and fluorescence mode. The intensity grade of the tissue fluorescence was categorisized by the surgeon in three grades, highly fluorescent, weakly fluorescent and not fluorescent. In these areas tissue samples were taken and investigated by two blinded independent neuropathologists. Tissue samples were histologically classified differentiating between tumor tissue, tumor necrosis, tissue with scattered tumor cells and normal brain tissue. RESULTS In all patients tumor tissue was clearly distinguishable by its typically red fluorescence color from normal brain tissue which was colored blue under a special fluorescent filter. Histological evaluation of the 110 tissue samples showed a specificity of 100% and sensitivity of 91% for one of the two neuropathologists, whereas specificity for second pathologist was 90% and sensitivity 94%. The i.v. application of Hypericin proofed to be safe in all cases and there were no side effects observed. CONCLUSION Hypericin in its water soluble form is a well tolerated drug. In addition to its high photosensitizing properties hypericin will open up interesting new therapeutic possibilities especially when used in combination with fluorescence detection and simultaneously photodynamic therapy.

Use of 5-ALA fluorescence guided endoscopic biopsy of a deep-seated primary malignant brain tumor

The introduction of fluorescence-guided resection of primary malignant brain tumors was a milestone in neurosurgery. Deep-seated malignant brain tumors are often not approachable for microsurgical resection. For diagnosis and therapy, new strategies are recommended. The combination of endoscopy and 5-aminolevulinic acid-induced protoporphyrin IX (5-ALA-induced Pp IX) fluorescence-guided procedures supported by neuronavigation seems an interesting option. Here the authors report on a combined approach for 5-ALA fluorescence-guided biopsy in which they use an endoscopy system based on an Xe lamp (excitation approximately λ = 407 nm; dichroic filter system λ = 380-430 nm) to treat a malignant tumor of the thalamus and perform a ventriculostomy and septostomy. The excitation filter and emission filter are adapted to ensure that the remaining visible blue remission is sufficient to superimpose on or suppress the excited red fluorescence of the endogenous fluorochromes. The authors report that the lesion was easily detectable in the fluorescence mode and that biopsy led to histological diagnosis.

Selective enrichment of hypericin in malignant glioma: pioneering in vivo results.

Malignant gliomas are diffuse infiltrative growing tumors with a poor prognosis despite treatment with a combination of surgery, radiotherapy and chemotherapy. It has been shown recently that complete tumor resection improves the survival time significantly. Hypericin, a component of St. Johns Wort, is one of the most powerful photosensitizers in nature. The aim of the present study was to investigate accumulation of hypericin in intracerebral implanted malignant glioma in vivo. Rats underwent stereotactic implantation of C6 glioma cells. After intravenous administration of hypericin (5 mg per kg body weight), accumulation of the compound was studied in tumor, the infiltration zone surrounding the tumor and healthy brain (contralateral hemisphere) by fluorescence microscopy between 0 and 48 h after injection. Results were compared by one-way analysis of variance. For post hoc pair-wise comparison the Tukey-Kramer HSD test was used. Accumulation of hypericin was significantly higher in C6 glioma as compared to normal tissue. Maximum hypericin uptake was achieved at 24 h after injection. Ratios of fluorescence intensity between tumor and normal tissue as well as infiltration zone and normal tissue of about 6.1:1 and 1.4:1 were found. Considering tissue auto-fluorescence, fluorescence ratios of about 19.8:1 and 2.5:1 were calculated, respectively. Therefore, hypericin seems to be quite an effective fluorescence marker for the detection of glioma in vivo. To the best of our knowledge, the present study demonstrates for the first time that hypericin accumulates selectively in intracerebral implanted C6 glioma in vivo after systemic (intravenous) administration.