Robot-assisted spinal augmentation procedures: is it worth the increased effort?

PURPOSE: Spinal augmentation procedures (SAP) are standard procedures for vertebral compression fractures. Often, SAPs are carried out in a minimally invasive, percutaneous way. Certain anatomic conditions such as small pedicles or kyphotic deformities resulting from a significant collapse of the vertebral body might render the operation more difficult and increase the risk of complications. Thus, robot assistance might be useful to optimize the trajectory and to reduce procedure-associated complications. In this study robot-assisted percutaneous SAPs are compared with conventional fluoroscopy-guided percutaneous SAP. METHODS: A retrospective observational analysis was carried out. Standard demographic parameters were analyzed. Procedural data including radiation dosage records were screened. Biomechanical data were recorded. Cement volumes were analyzed. The precision of the pedicular trajectory was reviewed, and misplaced trajectories were categorized. Procedure-associated complications were analyzed and evaluated for their clinical significance. RESULTS: A total of 130 procedures were reviewed, and 94 patients were finally included. Osteoporotic fractures (OF) were the main indication (60.7%; OF 2-44%, OF 4-33%). Demographic parameters and clinically relevant complications were equally distributed between the two groups. Duration of surgery was significantly longer in robot-assisted procedures (p < 0.001). Intraoperative radiation exposure was equally distributed. Injected cement volume was similar in both groups. There was no significant difference in pedicle trajectory deviation. CONCLUSION: The use of robot assistance in SAP seems not to be superior with regard to accuracy, radiation exposure and the rate of complications when compared to fluoroscopy-guided SAP.

Surgery for brain metastases: radiooncology scores predict survival-score index for radiosurgery, graded prognostic assessment, recursive partitioning analysis.

BACKGROUND: Radiooncological scores are used to stratify patients for radiation therapy. We assessed their ability to predict overall survival (OS) in patients undergoing surgery for metastatic brain disease. METHODS: We performed a post-hoc single-center analysis of 175 patients, prospectively enrolled in the MetastaSys study data. Score index of radiosurgery (SIR), graded prognostic assessment (GPA), and recursive partitioning analysis (RPA) were assessed. All scores consider age, systemic disease, and performance status prior to surgery. Furthermore, GPA and SIR include the number of intracranial lesions while SIR additionally requires metastatic lesion volume. Predictive values for case fatality at 1 year after surgery were compared among scoring systems. RESULTS: All scores produced accurate reflections on OS after surgery (p ≤ 0.003). Median survival was 21-24 weeks in patients scored in the unfavorable cohorts, respectively. In cohorts with favorable scores, median survival ranged from 42 to 60 weeks. Favorable SIR was associated with a hazard ratio (HR) of 0.44 [0.29, 0.66] for death within 1 year. For GPA, the HR amounted to 0.44 [0.25, 0.75], while RPA had a HR of 0.30 [0.14, 0.63]. Overall test performance was highest for the SIR. CONCLUSIONS: All scores proved useful in predicting OS. Considering our data, we recommend using the SIR for preoperative prognostic evaluation and counseling.

High Periventricular T1 Relaxation Times Predict Gait Improvement After Spinal Tap in Patients with Idiopathic Normal Pressure Hydrocephalus.

PURPOSE: The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) can be challenging. Aim of this study was to use a novel T1 mapping method to enrich the diagnostic work-up of patients with suspected iNPH. METHODS: Using 3T magnetic resonance imaging (MRI) we prospectively evaluated rapid high-resolution T1 mapping at 0.5 mm resolution and 4 s acquisition time in 15 patients with suspected iNPH and 8 age-matched, healthy controls. T1 mapping in axial sections of the cerebrum, clinical and neuropsychological testing were performed prior to and after cerebrospinal fluid tap test (CSF-TT). T1 relaxation times were measured in 5 predefined periventricular regions. RESULTS: All 15 patients with suspected iNPH showed gait impairment, 13 (86.6%) showed signs of cognitive impairment and 8 (53.3%) patients had urinary incontinence. Gait improvement was noted in 12 patients (80%) after CSF-TT. T1 relaxation times in all periventricular regions were elevated in patients with iNPH compared to controls with the most pronounced differences in the anterior (1006 ± 93 ms vs. 911 ± 77 ms; p = 0.023) and posterior horns (983 ± 103 ms vs. 893 ± 68 ms; p = 0.037) of the lateral ventricles. Montreal cognitive assessment (MoCA) scores at baseline were negatively correlated with T1 relaxation times (r < -0.5, p < 0.02). Higher T1 relaxation times were significantly correlated with an improvement of the 3­m timed up and go test (r > 0.6 and p < 0.03) after CSF-TT. CONCLUSION: In iNPH-patients, periventricular T1 relaxation times are increased compared to age-matched controls and predict gait improvement after CSF-TT. T1 mapping might enrich iNPH work-up and might be useful to indicate permanent shunting.

In vitro testing of explanted shunt valves in hydrocephalic patients with suspected valve malfunction.

Diagnosis of symptomatic valve malfunction in hydrocephalic patients treated with VP-Shunt (VPS) might be difficult. Clinical symptoms such as headache or nausea are nonspecific, hence cerebrospinal fluid (CSF) over- or underdrainage can only be suspected but not proven. Knowledge concerning valve malfunction is still limited. We aim to provide data on the flow characteristics of explanted shunt valves in patients with suspected valve malfunction. An in vitro shunt laboratory setup was used to analyze the explanted valves under conditions similar to those in an implanted VPS. The differential pressure (DP) of the valve was adjusted stepwise to 20, 10, 6, and 4 cmH2O. The flow rate of the explanted and the regular flow rate of an identical reference valve were evaluated at the respective DPs. Twelve valves of different types (Codman CertasPlus valve n = 3, Miethke Shuntassistant valve n = 4, Codman Hakim programmable valve n = 3, DP component of Miethke proGAV 2.0 valve n = 2) from eight hydrocephalic patients (four male), in whom valve malfunction was assumed between 2016 and 2017, were replaced with a new valve. Four patients suffered from idiopathic normal pressure (iNPH), three patients from malresorptive and one patient from obstructive hydrocephalus. Post-hoc analysis revealed a significant difference (p < 0.001) of the flow rate between each explanted valve and their corresponding reference valve, at each DP. In all patients, significant alterations of flow rates were demonstrated, verifying a valve malfunction, which could not be objectified by the diagnostic tools used in the clinical routine. In cases with obscure clinical VPS insufficiency, valve deficiency should be considered.

Angulation Toward Coronal Convexity Measure and Catheter Length Indication Improves the Quality of Ventricular Catheter Placement-A Smartphone-Assisted Guidance Technique.

BACKGROUND: Accurate placement of a ventricular catheter (VC) is crucial to reduce the risk of shunt failure. In the randomized, prospective, multicenter GAVCA (guided application of ventricular catheters) trial, which evaluated the quality of VC placement, the subgroup of patients with detailed length-marked VCs (dVCs) reflected a difference in the primary endpoint of optimal VC placement compared with the subgroup of patients with simplified length-marked VCs (sVCs). The objective of the present analysis was to compare the dVC and sVC groups and the smartphone-assisted guidance technique (GA) with the standard freehand technique (FH) for VC placement. METHODS: We performed a further analysis of the GAVCA trial in 2 steps. First, we compared the dVCs, which provided a detailed distance from the tip to the base (3-13 cm) in 0.5-cm intervals, with the sVCs with a length indication at 5 and 10 cm from the tip to base. Second, we compared the GA technique with the FH in the dVC group. RESULTS: The data from 137 patients (104 dVC patients vs. 33 sVC patients) were eligible for the present analysis. Optimal VC placement was achieved in 72.1% of the dVC group and 39.4% of the sVC group (odds ratio, 3.9; 95% confidence interval, 1.7-9.3; P ≤ 0.001). In addition, we performed a subgroup analysis of the 104 dVC patients concerning the accuracy of catheter placement using 2 different techniques (GA, n = 54; and FH, n = 50). Optimal catheter placement was achieved in 81.5% of the GA group and 62.0% of the FH group (odds ratio, 2.7; 95% confidence interval, 1.1-6.8; P = 0.03). VC placement using the GA technique was successful in all patients at the primary puncture. In contrast, for 8.7% of the patients in the FH group, multiple attempts were necessary (P = 0.03). CONCLUSIONS: The results from the present analysis suggest that the combination of a GA technique and the use of a dVC will improve the rate of accurate VC placement. Compared with the FH technique, patient safety was increased by the reduction of unsuccessful VC placement attempts using the GA technique and dVCs.

Correlation between different instrumentation variants and the degree of destabilization in treating cervical spondylotic spinal canal stenosis by unilateral hemilaminectomy with bilateral decompression: a biomechanical investigation.

PURPOSE: Unilateral hemilaminectomy with bilateral decompression (BDZ) was proposed as an alternative decompressive procedure in cervical spondylotic myelopathy (CSM). Despite promising clinical results, the destabilizing effect is yet unknown. We therefore performed a biomechanical study to investigate whether lateral mass screw fixation should follow BDZ. METHODS: Six human C2-C7 cervical specimens were tested under various conditions: native, unilateral hemilaminectomy with bilateral decompression without/with fixation (BDZ/BDF), unilateral hemilaminectomy with bilateral decompression and unilateral foraminotomy without/with fixation (UFZ/UFF), unilateral hemilaminectomy with bilateral decompression and bilateral foraminotomy without/with fixation (BFZ/BFF), and laminectomy without/with fixation (LAZ/LAF). Instrumention was applied from C3-C6. For each condition, the three-dimensional kinematics of the cervical specimen were measured in three main loading directions with an ultrasonic motion analysis system. ANOVA was used to determine differences between the specific segment conditions to assess the parameter's range of motion (ROM) and neutral zone (NZ). RESULTS: For flexion-extension, lateral bending and axial rotation, ROM of BDZ, UFZ, BFZ and LAZ remained at the level of the native condition (p > 0.74), whereas fixation reduced ROM significantly (p < 0.01). Between BDF, UFF, BFF and LAF, no significant differences in reduction in ROM were seen (p > 0.49). Results for NZ were equivalent to ROM in flexion-extension and lateral bending. For axial rotation, NZ remained almost constant on the native level for all tested conditions. CONCLUSION: Bilateral decompression via a hemilaminectomy, even if combined with foraminotomy, could be a less invasive treatment option for multilevel CSM in patients with lordotic cervical alignment and absence of segmental instability.

Survival after resection of brain metastases with white light microscopy versus fluorescence-guidance: A matched cohort analysis of the Metastasys study data.

BACKGROUND: Metastatic brain disease continues to have a dismal prognosis. Previous studies achieved a reduction of local recurrence rates by aggressively resecting the peritumoral zone (supramarginal resection) or using 5-aminolaevulinic acid (5-ALA) fluorescence. The aim of the present study is to assess whether the use of 5-ALA has an impact on local recurrence or survival compared to conventional white light microscopic tumor resection. MATERIALS AND METHODS: We included consecutive patients who underwent surgical resection of brain metastases. Two groups were compared: In the "white light" group, resection was performed with conventional microscopy. In the 5-ALA group, fluorescence guided peritumoral resection was additionally performed after standard microscopic resection. In-brain recurrence and mortality were compared between groups. RESULTS: N = 175 patients were included in the study. All baseline parameters were similarly distributed with no significant difference between surgical groups. Local in-brain recurrence occurred in 21/175 patients (12%) with a rate of 15/119 (12.6%) in the white light and 6/56 (10.7%) in the 5-ALA group (p = 0.720). The use of 5-ALA influenced neither in-brain recurrence (OR 0.59 [CI = 95% 0.18; 1.99], p = 0.40) nor mortality (OR 0.71 [CI = 95% 0.27; 1.85], p = 0.49). CONCLUSIONS: The use of 5-ALA did not result in lower in-brain recurrence or mortality compared to the use of white light microscopy. The most prominent predictors of survival remain favorable preoperative performance status, a low tumor diameter and the absence of multiple cerebral lesions.

Volumetric analysis of bilateral spinal canal decompression via hemilaminectomy versus laminoplasty in cervical spondylotic myelopathy.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a degenerative process of the cervical spine requiring surgical decompression to prevent neurological deterioration. While both anterior and posterior approaches yield satisfactory results, posterior decompression is preferred in cases of the multilevel disease. In 2015, we described a muscle-sparing, novel technique of bilateral osteoligamentous decompression via hemilaminectomy (OLD) for CSM. In this study, we investigate whether this technique offers comparable volumetric results to laminoplasty in terms of spinal canal enlargement and whether this technique can yield significant clinical improvement. METHODS: Patients undergoing OLD due to CSM were prospectively enrolled in this study and then matched to and compared with a historic cohort of patients with CSM treated by laminoplasty. An independent sample t test was performed to analyze whether the volumetric gain in the two separate groups was statistically significant. Patients in the OLD cohort were clinically evaluated with the mJOA score preoperatively and 3 months postoperatively. To assess clinical improvement, a paired sample t test was performed. RESULTS: A total of 38 patients were included in the analysis: 19 underwent OLD and 19 underwent laminoplasty. Both groups were well matched in terms of sex, age, preoperative spinal canal volume, and involved levels. Both surgical methods yielded statistically significant volumetric gain in the cervical spinal canal, but a trend towards a greater volume gain was seen in the OLD group. In the OLD group, a statistically significant clinical improvement was also demonstrated. CONCLUSIONS: Our study reveals that OLD can yield a comparable extent of decompression to laminoplasty in CSM while also delivering statistically significant clinical improvement.

Prophylactic enlargement of the thecal sac volume by spinal expansion duroplasty in patients with unresectable malignant intramedullary tumors and metastases prior to radiotherapy.

Unresectable malignant intramedullary tumors and metastases usually require radiotherapy which intensifies spinal cord edema and might result in neurological decline. Spinal expansion duroplasty before radiotherapy enlarges the intrathecal volume and might thus prevent neurological deficits. The study aims to evaluate the clinical course of patients undergoing expansion duroplasty. This retrospective analysis (2007-2016) included all patients with unresectable intramedullary tumors who underwent spinal expansion duroplasty. To assess the degree of preoperative cord enlargement, we calculated the "diameter ratio": diameter of the spinal cord below and above the tumor / diameter of the tumor × 2. The presence of perimedullary cerebrospinal fluid (CSF) at the affected levels was analyzed on the preoperative magnetic resonance imaging (MRI). We recorded the occurrence of neurological deficits, wound breakdown, and CSF fistula. We screened 985 patients, 11 of which were included. Eight patients had an intramedullary metastasis, three patients a spinal malignant glioma. A diameter ratio ≤ 0.8 representing a significant preoperative intramedullary enlargement was seen in 10 cases (90.9%). Postoperative imaging was available in 9 patients, demonstrating successful decompression in 8 of the 9 patients (88.9%). The postoperative course was uneventful in 9 patients (81.8%). Mean overall survival was 13.4 (SD 16.2) months. Spinal expansion duroplasty prior to radiotherapy is a previously undescribed concept. Despite neoadjuvant radiation, no wound breakdown or CSF fistula occurred. In unresectable intramedullary tumors and metastases, spinal expansion duroplasty seems to be a safe procedure with the potential to prevent neurological decline due to radiation-induced cord swelling.

The European Robotic Spinal Instrumentation (EUROSPIN) study: protocol for a multicentre prospective observational study of pedicle screw revision surgery after robot-guided, navigated and freehand thoracolumbar spinal fusion.

INTRODUCTION: Robotic guidance (RG) and computer-assisted navigation (NV) have seen increased adoption in instrumented spine surgery over the last decade. Although there exists some evidence that these techniques increase radiological pedicle screw accuracy compared with conventional freehand (FH) surgery, this may not directly translate to any tangible clinical benefits, especially considering the relatively high inherent costs. As a non-randomised, expertise-based study, the European Robotic Spinal Instrumentation Study aims to create prospective multicentre evidence on the potential comparative clinical benefits of RG, NV and FH in a real-world setting. METHODS AND ANALYSIS: Patients are allocated in a non-randomised, non-blinded fashion to the RG, NV or FH arms. Adult patients that are to undergo thoracolumbar pedicle screw instrumentation for degenerative pathologies, infections, vertebral tumours or fractures are considered for inclusion. Deformity correction and surgery at more than five levels represent exclusion criteria. Follow-up takes place at 6 weeks, as well as 12 and 24 months. The primary endpoint is defined as the time to revision surgery for a malpositioned or loosened pedicle screw within the first postoperative year. Secondary endpoints include patient-reported back and leg pain, as well as Oswestry Disability Index and EuroQOL 5-dimension questionnaires. Use of analgesic medication and work status are recorded. The primary analysis, conducted on the 12-month data, is carried out according to the intention-to-treat principle. The primary endpoint is analysed using crude and adjusted Cox proportional hazards models. Patient-reported outcomes are analysed using baseline-adjusted linear mixed models. The study is monitored according to a prespecified monitoring plan. ETHICS AND DISSEMINATION: The study protocol is approved by the appropriate national and local authorities. Written informed consent is obtained from all participants. The final results will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Clinical Trials.gov registry NCT03398915; Pre-results, recruiting stage.

Cerebral metastases: do size, peritumoral edema, or multiplicity predict infiltration into brain parenchyma?

BACKGROUND: Brain metastases (BMs) are the most frequent malignancy of the central nervous system. Previous research suggested that some metastases show infiltrative behavior rather than sharp demarcation. We hypothesized that three magnetic resonance (MR) imaging parameters-(a) tumor size, (b) extent of peritumoral edema, and (c) presence of multiple BMs-are predictors of cellular invasion beyond the surgically identifiable tumor margins. METHODS: We performed a post hoc analysis on prospectively collected data of patients with BMs. Biopsies beyond the resection margin and immunohistochemistry were performed to assess infiltration status. The three MR imaging parameters were dichotomized into diameters ≤ 30 mm ("small") and > 30 mm ("large"), amount of peritumoral edema "extended" and "limited," and "multiple BMs" and "single BMs," respectively. The association between infiltration status and imaging parameters was calculated using chi-square test. RESULTS: Biopsy beyond the resection margin was performed in 77 patients; 49 (63.6%) had supramarginal infiltration and 28 patients (36.4%) showed no infiltration. Histological evidence of tumor infiltration was found in 25/41 patients with smaller lesions (61%) and in 24/36 with larger lesions (66.7%, p = 0.64), in 28/44 patients with limited (63.6%) and in 21/33 patients with extended edema (63.6%, p = 1.0), in 28/45 patients (62.2%) with single BM and in 21/32 patients (65.6%) with multiple BMs (p = 0.81). CONCLUSIONS: Based on the post hoc analysis of our prospective trial data, we could not confirm the hypothesis that infiltration of brain parenchyma beyond the glial pseudocapsule is associated with the MR imaging parameters tumor size, extent of edema, or multiplicity of metastases.

Infarct volume predicts outcome after decompressive hemicraniectomy for malignant hemispheric stroke.

The decision to perform decompressive hemicraniectomy (DHC) by default in malignant hemispheric stroke (MHS) remains controversial. Even under ideal conditions, DHC usually results in moderate to severe disability. The present study for the first time uses neuroimaging to identify independent outcome predictors in a prospective cohort of 96 MHS patients undergoing DHC. The primary outcome was functional status according to the modified Rankin Scale (mRS) at 12 months and categorized as favorable (mRS 0-3) or unfavorable (mRS 4-6). At 12 months, 19 patients (20%) reached favorable and 77 patients (80%) unfavorable outcome. The overall mean infarct volume was 328 ± 114 ml. Multivariable logistic regression identified age per year (OR 1.14, 95% CI 1.04-1.24; p = 0.005), infarct volume per cm3 (OR 1.012, 95% CI 1.003-1.022; p = 0.013), thalamic involvement (OR 8.65, 95% CI 1.04-72.15; p = 0.046) and postoperative pneumonia (OR 5.52, 95% CI 1.03-29.57; p = 0.046) as independent outcome predictors, which was confirmed by multivariable ordinal regression for age ( p = 0.004) and infarct volume ( p = 0.015). The infarct volume threshold for reasonable prediction of unfavorable outcome in our patients was 270 cm3, which in the future may help prognostication and development of clinical trials on DHC and outcome in MHS.

A counterforce to diversion of cerebrospinal fluid during ventriculoperitoneal shunting: the intraperitoneal pressure. An observational study.

BACKGROUND: Intraperitoneal pressure (IPP) counteracts the diversion of cerebrospinal fluid (CSF) from the cranial to the peritoneal compartment during ventriculoperitoneal shunting. Animal studies suggest that the intrinsic IPP exceeds the intraperitoneal hydrostatic pressure. The intrinsic IPP in mobile patients is relevant for shunt therapy, but data about it is not available. METHODS: The IPP was measured indirectly in 25 mobile subjects (13 female) by applying a standard intravesical pressure measurement technique. Measurements were carried out in reference to the navel (supine position) and the xiphoid (upright position). Results were adjusted for the intraperitoneal hydrostatic pressure and correlated afterward with general body measures. RESULTS: The corrected mean (SD) IPP measured in the supine position was 4.4 (4.5) cm H2O, and the mean (SD) upright IPP was 1.6 (7.8) cm H2O (p = 0.02). A positive correlation was found between the body mass index (BMI) and the IPP in the upright (r = 0.51) and supine (r = 0.65) body positions, and between the abdominal circumference and the IPP in the supine position (r = 0.63). CONCLUSIONS: The intrinsic IPP in mobile subjects exceeds the intraperitoneal hydrostatic pressure. Thus, the intrinsic IPP counteracts the diversion of CSF into the peritoneal compartment. The intrinsic IPP is correlated with mobile patients' general body measures.

Large Size Hemicraniectomy Reduces Early Herniation in Malignant Middle Cerebral Artery Infarction.

BACKGROUND: Decompressive hemicraniectomy (DHC) reduces mortality and improves outcome after malignant middle cerebral artery infarction (MMI) but early in-hospital mortality remains high between 22 and 33%. Possibly, this circumstance is driven by cerebral herniation due to space-occupying brain swelling despite decompressive surgery. As the size of the removed bone flap may vary considerably between surgeons, a size too small could foster herniation. Here, we investigated the effect of the additional volume created by an extended DHC (eDHC) on early in-hospital mortality in patients suffering from MMI. METHODS: We performed a retrospective single-center cohort study of 97 patients with MMI that were treated either with eDHC (n = 40) or standard DHC (sDHC; n = 57) between January 2006 and June 2012. The primary study end point was defined as in-hospital mortality due to transtentorial herniation. RESULTS: In-hospital mortality due to transtentorial herniation was significantly lower after eDHC (0 vs. 11%; p = 0.04), which was paralleled by a significantly larger volume of the craniectomy (p < 0.001) and less cerebral swelling (eDHC 21% vs. sDHC 25%; p = 0.03). No statistically significant differences were found in surgical or non-surgical complications and postoperative intensive care treatment. CONCLUSION: Despite a more aggressive surgical approach, eDHC may reduce early in-hospital mortality and limit transtentorial herniation. Prospective studies are warranted to confirm our results and assess general safety of eDHC.

Delayed cerebral ischemia and spreading depolarization in absence of angiographic vasospasm after subarachnoid hemorrhage.

It has been hypothesized that vasospasm is the prime mechanism of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Recently, it was found that clusters of spreading depolarizations (SDs) are associated with DCI. Surgical placement of nicardipine prolonged-release implants (NPRIs) was shown to strongly attenuate vasospasm. In the present study, we tested whether SDs and DCI are abolished when vasospasm is reduced or abolished by NPRIs. After aneurysm clipping, 10 NPRIs were placed next to the proximal intracranial vessels. The SDs were recorded using a subdural electrode strip. Proximal vasospasm was assessed by digital subtraction angiography (DSA). 534 SDs were recorded in 10 of 13 patients (77%). Digital subtraction angiography revealed no vasospasm in 8 of 13 patients (62%) and only mild or moderate vasospasm in the remaining. Five patients developed DCI associated with clusters of SD despite the absence of angiographic vasospasm in three of those patients. The number of SDs correlated significantly with the development of DCI. This may explain why reduction of angiographic vasospasm alone has not been sufficient to improve outcome in some clinical studies.

Modified flow- and oxygen-related autoregulation indices for continuous monitoring of cerebral autoregulation.

Continuous monitoring of brain tissue partial pressure of oxygen (ptiO(2)), thermal-diffusion regional cerebral blood flow (TD-rCBF) and cerebral perfusion pressure (CPP) allows the calculation of flow- and oxygen-related autoregulation indices ORx and FRx. The influence of temporal phase shifts on ORx and FRx due to a delay in the response time of ptiO(2) and TD-rCBF has received little attention. We investigated the impact of phase shifts between changes in CPP and the corresponding ptiO(2) and TD-rCBF responses on the degree of correlation of ORx and FRx. In five patients with aneurysmal subarachnoid hemorrhage continuous multimodal neuromonitoring was performed for 7-10 days. In each patient the phase shift of the ptiO(2)- and TD-rCBF-response after spontaneous positive or negative CPP fluctuations during two 1-h time periods of disturbed cerebral autoregulation was determined. For these periods, ORx and FRx were calculated as Pearson correlation coefficients before (ORx and FRx) and after (ORx(sync) and FRx(sync)) temporal synchronization of ptiO(2), TD-rCBF and CPP. The mean temporal phase shift after CPP fluctuations was 65±11 s for ptiO(2) and 12±4 s for TD-rCBF. Before synchronization, ORx and FRx were determined at 0.52±0.3 and 0.59±0.3, respectively. After synchronization, ORx(sync) and FRx(sync) correlated significantly stronger than unsynchronized indices (ORx(sync): 0.66±0.3; FRx(sync): 0.62±0.3; p<0.01 vs. ORx and FRx, respectively). These findings suggest that ORx and FRx are subject to temporal latency shifts of ptiO(2) and TD-rCBF in regard to spontaneous CPP fluctuations. Temporal synchronization for the calculation of both ORx and FRx may permit continuous monitoring of these indices with higher sensitivity.

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.

Use of gelatin-thrombin matrix hemostatic sealant in cranial neurosurgery.

The present study evaluated the hemostatic efficacy and handling of gelatin-thrombin matrix hemostatic sealant during intracranial procedures. A retrospective analysis of 478 consecutive patients undergoing intracranial procedures identified seven patients with acute intense or persistent intraoperative bleeding which could not be arrested in time by standard hemostatic methods. The efficacy of gelatin-thrombin matrix was assessed by determining bleeding severity before and after application, time to hemostasis, amount of gelatin-thrombin matrix necessary, need for additional hemostatic measures, and need for reoperation to control hemorrhage. Immediate hemostasis was achieved in five of seven patients. Two of these five patients had abnormal clotting parameters. Cessation of bleeding was achieved by additionally applying either fibrinogen or gelatin sponge to the bleeding site in the other two patients. No complications attributable to gelatin-thrombin matrix use were recorded. The gelatin-thrombin matrix was ready to use within 1 minute in every case. Gelatin-thrombin matrix appears to be an effective, easy-to-use, and readily available hemostatic agent for cranial neurosurgery. Combination with fibrinogen is recommended in special situations.

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 patient's recovery was prompt and complete.

Pharmacokinetics of taurolidine following repeated intravenous infusions measured by HPLC-ESI-MS/MS of the derivatives taurultame and taurinamide in glioblastoma patients.

BACKGROUND AND OBJECTIVE: Taurolidine 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 METHODS: The 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. RESULTS: The 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 microg/mL, and 1.69 at 100 microg/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. CONCLUSIONS: Taurolidine 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 therapeutically adequate mode of administration for the indication of glioblastoma.