Ruediger Stendel

Intraoperative microvascular Doppler ultrasonography in cerebral aneurysm surgery

OBJECTIVES Outcome of surgical treatment of cerebral aneurysms may be severely compromised by local cerebral ischaemia or infarction resulting from the inadvertent occlusion of an adjacent vessel by the aneurysm clip, or by incomplete aneurysm closure. It is therefore mandatory to optimise clip placement in situ to reduce the complication rate. The present study was performed to investigate the reliability of intraoperative microvascular Doppler ultrasonography (MDU) in cerebral aneurysm surgery, and to assess the impact of this method on the surgical procedure itself. METHODS Seventy five patients (19 men, 56 women, mean age 54.8 years, range 22-84 years) with 90 saccular cerebral aneurysms were evaluated. Blood flow velocities in the aneurysmal sac and in the adjacent vessels were determined by MDU before and after aneurysm clipping. The findings of MDU were analysed and compared with those of visual inspection of the surgical site and of postoperative angiography. Analysis was also made of the cases in which the clip was repositioned due to MDU findings. RESULTS A relevant stenosis of an adjacent vessel induced by clip positioning that had escaped detection by visual inspection was identified by Doppler ultrasonography in 17 out of 90 (18.9%) aneurysms. In addition, Doppler ultrasound demonstrated a primarily unoccluded aneurysm in 11 out of 90 (12.2%) patients. The aneurysm clip was repositioned on the basis of the MDU findings in 26 out of 90 (28.8%) cases. In middle cerebral artery (MCA) aneurysms, the MDU results were relevant to the surgical procedure in 17 out of 44 (38.6%) cases. Whereas with aneurysms of the anterior cerebral artery significant findings occurred in only five of 32cases (15.6%; p<0.05). The clip was repositioned on the basis of the MDU results in 18 out of 50 (36%) aneurysms in patients with subarachnoid haemorrhage (SAH) grade I-V compared with only eight out of 40 (20%) aneurysms in patients without SAH (p<0.05). CONCLUSIONS MDU should be used routinely in cerebral aneurysm surgery, especially in cases of MCA aneurysms and after SAH. Present data show that a postoperative angiography becomes superfluous whenever there is good visualisation of the “working site” and MDU findings are clear.

Efficacy and safety of a collagen matrix for cranial and spinal dural reconstruction using different fixation techniques

OBJECT The use of dural grafts is frequently unavoidable when tension-free dural closure cannot be achieved following neurosurgical procedures or trauma. Biodegradable collagen matrices serve as a scaffold for the regrowth of natural tissue and require no suturing. The aim of this study was to investigate the efficacy and safety of dural repair with a collagen matrix using different fixation techniques. METHODS A total of 221 patients (98 male and 123 female; mean age 55.6 +/- 17.8 years) undergoing cranial (86.4%) or spinal (13.6%) procedures with the use of a collagen matrix dural graft were included in this retrospective study. The indications for use, fixation techniques, and associated complications were recorded. RESULTS There were no complications of the dural graft in spinal use. Five (2.6%) of 191 patients undergoing cranial procedures developed infections, 3 of which (1.6%) were deep infections requiring surgical revision. There was no statistically significant relationship between the operative field status before surgery and the occurrence of a postoperative wound infection (p = 0.684). In the 191 patients undergoing a cranial procedure, cerebrospinal fluid (CSF) collection occurred in 5 patients (2.6%) and a CSF fistula in 5 (2.6%), 3 of whom (1.6%) required surgical revision. No patient who underwent an operation with preexisting CSF leakage had postoperative CSF leakage. Postoperative infection significantly increased the risk for postoperative CSF leakage. The collagen matrix was used without additional fixation in 124 patients (56.1%), with single fixation in 55 (24.9%), and with multiple fixations in 42 (19%). There were no systemic allergic reactions or local skin changes. Follow-up imaging in 112 patients (50.7%) revealed no evidence of any adverse reaction to the collagen graft. CONCLUSIONS The collagen matrix is an effective and safe cranial and spinal dural substitute that can be used even in cases of an existing local infection. Postoperative deep infection increases the risk for CSF leakage.

Assessment of 3D-TOF-MRA at 3.0 tesla in the characterization of the angioarchitecture of cerebral arteriovenous malformations: a preliminary study:

Background: The characterization of brain arteriovenous malformation (AVM) angioarchitecture remains rewarding in planning and predicting therapy. The increased signal-to-noise ratio at higher field strength has been found advantageous in vascular brain pathologies. Purpose: To evaluate whether 3.0T time-of-flight (TOF) magnetic resonance angiography (MRA) is superior to 1.5T TOF-MRA for the characterization of cerebral AVMs. Material and Methods: Fifteen patients with AVM underwent TOF-MRA at 3.0T and 1.5T and catheter angiography (DSA), which was used as the gold standard. Blinded readers scored image quality on a four-point scale, nidus size, and number of feeding arteries and draining veins. Results: Image quality of TOF-MRA at 3.0T was superior to 1.5T but still inferior to DSA. Evaluation of nidus size was equally good at 3.0T and 1.5T for all AVMs. In small AVMs, however, there was a tendency of size overestimation at 3.0T. MRA at 3.0T had increased detection rates for feeding arteries (+21%) and superficial (+13%) and deep draining veins (+33%) over 1.5T MRA. Conclusion: 3.0T TOF-MRA offers superior characterization of AVM angioarchitecture compared with 1.5T TOF-MRA. The image quality of MRA at both 3.0 and 1.5T is still far from equal to DSA, which remains the gold standard for characterization of AVM.

Injection therapy of lumbar facet syndrome: a prospective study

SummaryBackground. Chronic low back pain remains a major health problem. Facet joint injection therapy is an easy to perform therapeutic option. However, few prospective studies use a standardized protocol to investigate injection therapy. The aim of our study was to evaluate quantity and duration of clinical improvement after this protocol, and to identify the best time for additional repetitive injection therapy.Materials and Methods. Thirty-nine patients (21 men, 18 women; mean age 55.2 years [range, 29–87 years]) with lumbar facet syndrome were treated with injection using a standardized protocol (prednisolone acetate, lidocaine 1%, phenol 5%) under fluoroscopic control. Follow-up was based on a specially designed questionnaire. Analysis included MacNab criteria, visual analogue scale, and pain disability index.Results. Reduction of pain was found up to 6 months after treatment. The outcome was assessed excellent or good by 62% (24 patients) of the patients after 1 month, by 41% (16 patients) after 3 months, and by 36% (14 patients) after 6 months. There was no influence of age, body mass index, or previous lumbar spinal surgery on improvement after treatment. There were no severe side effects. Short-lasting self limiting mild side effects were found in 26% (increased back pain, numbness, heartburn, headache, allergy).Conclusion. Facet joint injection therapy using a standardized protocol is safe, effective, and easy to perform. The clinical effect is limited, and we recommend repetitive injection according to this protocol after 3 months.

Pharmacokinetics of Taurolidine following Repeated Intravenous Infusions Measured by HPLC-ESI-MS/MS of the Derivatives Taurultame and Taurinamide in Glioblastoma Patients

Background and objectiveTaurolidine is known to have antimicrobial activity. Furthermore, at lower concentrations, it has been found to exert a selective antineoplastic effect in vitro and in vivo. The aim of this study was to investigate the pharmacokinetics of taurolidine in vivo following repeated intravenous infusion in a schedule used for the treatment of glioblastoma. As a prerequisite, the pharmacokinetics of taurolidine in human blood plasma and whole blood in vitro was investigated.Patients and methodsThe pharmacokinetics of taurolidine and its derivatives taurultame and taurinamide were investigated in human blood plasma and in whole blood in vitro using blood from a healthy male volunteer. During repeated intravenous infusion therapy with taurolidine, plasma samples were taken every hour for a period of 13 hours per day in seven patients (three male, four female; mean age 48.4 ± 12.8 years, range 27–66 years) with a glioblastoma. Following dansyl derivatisation, the concentrations of taurultame and taurinamide were determined using a new method based on high-performance liquid chromatography (HPLC) online coupled to electrospray ionisation tandem mass spectrometry (ESI-MS/MS) in the multiple reaction monitoring mode. Under the experimental conditions used, taurolidine could not be determined directly and was back-calculated from the taurultame and taurinamide values.ResultsThe new HPLC-ESI-MS/MS method demonstrated high accuracy and reproducibility. In vitro plasma concentrations of taurultame and taurinamide remained constant over the incubation period. In whole blood in vitro, a time-dependent formation of taurinamide was observed. At the start of the incubation, the taurultame-taurinamide ratio (TTR) was 0.95 at an initial taurolidine concentration of 50 μg/mL, and 1.69 at 100 μg/mL. The concentration of taurultame decreased at the same rate as the taurinamide concentration increased, showing logarithmic kinetics. The calculated taurolidine concentration remained largely constant over the 6-hour incubation period. During repeated infusions in patients, calculated plasma concentrations of taurolidine showed a strong increase after the start of each infusion and continued to increase until the end of infusion, followed by a rapid decline. The TTR was found to fluctuate between 0.1 and 0.3, depending on the relation to the previous or next infusion period. The volume of distribution was markedly higher for taurolidine, taurultame and taurinamide than the plasma volume.ConclusionsTaurolidine displayed a stable pattern of derivatives in plasma in vitro, whereas in whole blood, a time- and concentration-dependent conversion was apparent. In patients, the calculated average taurolidine plasma concentration, achieved with the repeated infusion regimen, was in the antineoplastic-effective concentration range. The tissue concentrations of taurolidine and taurultame are expected to be higher than the plasma concentrations, taking into account the calculated volumes of distribution. Repeated infusion of taurolidine is the thera-peutically adequate mode of administration for the indication of glioblastoma.

The antibacterial substance taurolidine exhibits anti-neoplastic action based on a mixed type of programmed cell death

The antibacterial amino-acid derivative taurolidine (TAU) has been recently shown to exhibit anti-neoplastic activity based on a mechanism, which is still unknown in detail. Cytotoxicity and clonogenic assays were performed and the impact of apoptosis modulators, a radical scavenger, autophagy inhibitors, silencing of apoptosis inducing actor (AIF) and cytochrome-c (Cyt-C) by siRNA, and knockdown of autophagy related genes were evaluated in vitro. The intracellular ATP-content, release of AIF and Cyt-C, and DNA-laddering were investigated. This study could demonstrate cell killing, inhibition of proliferation, and inhibition or prevention of colony formation in human glioma cell lines and ex vivo glioblastoma cells after incubation with TAU. This effect is based on the induction of a mixed type of programmed cell death with the main preference of autophagy, and involvement of senescence, necroptosis, and necrosis. This mechanism of action may open a new approach for therapeutic intervention.

Rapidly progressive paraplegia due to an extradural lumbar meningocele mimicking a cyst. Case report.

Unlike arachnoid meningoceles, arachnoid cysts frequently cause local pressure effects probably because there is no free communication between the cyst and the subarachnoid space. Following the first detailed description of cystic lesions of spinal nerve roots by Tarlov in 1938, a simplified classification of spinal meningeal cysts was developed in 1988, containing three major categories. The authors report on a lumbar intraspinal extradural meningocele that caused incomplete paraplegia in an otherwise healthy 31-year-old man in whom magnetic resonance imaging revealed stigmata of Scheuermann disease. Intraoperatively, the lesion was classified as a transitional-type lesion, in accordance with Type IA of the Nabors classification, because a communication with the subarachnoid space was observed. After complete removal of the meningocele, the patients recovery was prompt and complete.

Sensor-based neuronavigation: Evaluation of a large continuous patient population

OBJECTIVE Navigation systems enable neurosurgeons to guide operations with imaging data. Sensor-based neuronavigation uses an electromagnetic field and sensors to measure the positions of the patients brain anatomy and the surgical instruments. The aim of this investigation was to determine the accuracy level of sensor-based tracking in a large patient collection. METHODS This study covers 250 patients operated upon during a continuous 5.5-year period. The patients had a wide range of indications and surgical procedures. The operations were performed with a direct current (DC) pulsed sensor-based electromagnetic navigation system. Four kinds of errors were measured: the fiducial registration error (FRE), the target registration error (TRE), brain shift, and the position error (PE). These errors were calculated for five subgroups of indications: target determination and trajectory guidance, functional navigation, skull base and neurocranium, determination of resection volume, and transnasal and transsphenoidal access. RESULTS The overall mean FRE was 1.66mm (+/-0.61mm). The overall mean TREs were 1.33mm (+/-0.51mm) centroid and 1.59mm (+/-0.57mm) lesional. The overall mean brain shift for applicable cases was 1.61mm (+/-1.14mm). The overall mean PE was 0.92mm (+/-0.54mm). CONCLUSIONS By and large, modern sensor-based neuronavigation operates within an acceptable and commonplace degree of error. However, the neurosurgeon must remain critical in cases of small lesions, and must exert caution not to introduce further interference from metal objects or electromagnetic devices.

Giant intracerebral choroid plexus calcification

SummaryWhile small calcifications of the choroid plexus are frequent, a large, single intracerebral calcification originating from the choroid plexus is rare. This report presents a 27-year-old woman who was admitted because of right temporal headache which had persisted for months. There was no neurological deficit. Computed tomography demonstrated a mass of calcium density measuring approximately 3 × 3 × 4 cm in the right temporal region, extending to the temporal skull base and to the rostral edge of the petrous bone. At surgery a very hard, poorly vascularised tumour originating from the choroid plexus of the temporal horn of the right lateral ventricle was completely removed. Histological workup yielded the diagnosis of a markedly calcified choroid plexus with no indication of neoplasia or inflammation.Physiological intracranial calcifications resulting from local tissue dystrophy are usually incidental. In the case presented here, a large intracerebral choroid plexus calcification was detected in a patient presenting with episodes of severe headache. The potential pathogenetic mechanism is discussed.

Methodological Remarks on Transcranial Doppler Ultrasonography for PFO Detection

To the Editor:—With great interest and appreciation, we read the article of Stendel et al. about contrast-enhanced transcranial Doppler ultrasonography (c-TCD) for detection of a patent foramen ovale (PFO) before surgery in the sitting position. Although we agree that this is a significant alternative to the gold standard set by contrast-enhanced transesophageal echocardiography, we would like to make some methodologic remarks. Contrast-enhanced transcranial Doppler ultrasonography is an indirect approach to detect right-to-left shunting and does not allow for an exact anatomic localization of shunts. Precisely, in the mentioned diagnostic setting, a PFO is likely to cause high-intensity transient signals in c-TCD, but one should be aware that a PFO is not proven by this method. To ensure the diagnosis, contrast medium has to cross the atrial septum following the pressure gradient produced by a Valsalva maneuver during an interval of time that excludes pulmonary passage. Therefore, this interval should start with presence of contrast agent in the right atrium and should not exceed 10 cardiac cycles. Stendel et al. allow for 3–15 heart cycles after 5 s injection and 5 s Valsalva maneuver, following the protocol of Schwarze et al., but pulmonary arteriovenous fistulas can be a reason for the detection of high-intensity transient signals during the mentioned interval. In c-TCD, we frequently observe high-intensity transient signals that meet with the criteria to diagnose a PFO, whereas in contrast-enhanced transesophageal echocardiography, there is no evidence for it. These findings can be explained either by leakage of the capillary lung filter for microbubbles in some individuals or by pulmonary passage of contrast medium parts below standard size, despite correct preparation and handling of the D-Galactose contrast medium. When c-TCD is positive with Valsalva maneuver, we recommend an additional contrast injection without Valsalva maneuver to exclude pulmonary passage. In the normal heart cycle, an intermittent right-toleft pressure gradient occurs in the early systole because the tricuspidal valve physiologically closes a little earlier than does the mitral valve. Therefore, with c-TCD, even at rest an atrial septal defect or a permanent PFO allowing for spontaneous right-to-left shunting can be detected. Spontaneous right-to-left shunting indicates high hemodynamic relevance of the shunt and may be a valuable finding to select surgical and anesthesiologic procedures to avoid intraoperative paradoxical air embolism.