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  • Author or Editor: Andreas W. Unterberg x
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Stepan Fedorko, Klaus Zweckberger and Andreas W. Unterberg

OBJECTIVE

Pineal region tumors are a rare and heterogeneous group of lesions. The optimal therapeutic approach is currently a topic of controversy, particularly in light of the potential operative risks and complications. The potential beneficial effects of surgery have already been described, but information about neurological outcome and, in particular, health-related quality of life (HRQOL) is still lacking in the literature. The aim of this study was to assess the therapeutic effect of resection of pineal region lesions, emphasizing grade of tumor resection, neurological outcome, quality of life, and the necessity of additional shunt procedures.

METHODS

The authors performed a prospective study of HRQOL in 32 patients who had undergone surgical treatment of lesions in the pineal region (20 tumors and 12 cysts) between 2008 and 2014. All patients had at least 6 months of follow-up, with reexamination including standardized neurological assessment, an evaluation of dependency using the modified Rankin Scale, and an evaluation of HRQOL. The authors retrospectively examined patient charts and collected information regarding imaging studies, neurological status prior to surgery, surgical strategies used, any complications, and histological diagnoses.

RESULTS

In this study, there was no surgery-associated mortality or major morbidity. Permanent minor morbidity was reported for 4 patients (13%). Comparing pre- and postoperative neurological symptoms, 75% of tumor patients had either complete resolution or improvement of preoperative symptoms; symptoms were unchanged in 10% of tumor patients and deteriorated in 15%. In patients with pineal cysts, long-term follow-up showed that 42% of patients were free of any symptoms and 58% experienced improvement of their preoperative symptoms. These outcomes were also reflected in the modified Rankin Scale scores, which demonstrated significant improvement following resection of pineal region lesions. Furthermore, significant improvements in HRQOL scores occurred in global health status, in all functional scales, and in pain, nausea and vomiting, fatigue, and insomnia (p < 0.0001). Moreover, a significant reduction in the necessity for permanent shunt procedures was observed after gross-total tumor resection compared with subtotal resection (p = 0.035) of pineal cysts.

CONCLUSIONS

Despite potential risks, (radical) surgery is a highly effective and safe treatment option for pineal region lesions and should be considered for the majority of patients.

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Bruce J. Andersen, Andreas W. Unterberg, Geoff D. Clarke and Anthony Marmarou

✓ Cerebral energy metabolism was studied in cats subjected to fluid-percussion brain trauma followed immediately by 30 minutes of controlled hypoventilation for the purpose of simulating a more realistic model of human head injury. The cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2) and glucose (CMRGl) were measured, with simultaneous phosphorus-31 magnetic resonance spectroscopy quantifications of cerebral tissue pH, phosphocreatine (PCr), and inorganic phosphate (Pi). Hypoventilation alone did not produce marked changes in CMRGl, tissue pH, or PCr:Pi ratios. When hypoventilation was combined with trauma, marked alterations in CBF, CMRGl, PCr:Pi ratio, and tissue pH were seen, indicating relative ischemia. The alterations of cerebral energy metabolism produced by combining trauma and hypoventilation are more severe than those caused by fluid-percussion trauma alone, and may provide a more realistic model of human head injury.

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John F. Stover, Nils-Kristian Dohse and Andreas W. Unterberg

Object. Identification of new therapeutic agents aimed at attenuating posttraumatic brain edema formation remains an unresolved challenge. Among others, activation of bradykinin B2 receptors is known to mediate the formation of brain edema. The purpose of this study was to investigate the protective effect of the novel nonpeptide B2 receptor antagonist, LF 16-0687Ms, in brain-injured rats.

Methods. Focal contusion was produced by controlled cortical impact injury. Five minutes after trauma, the rats received a single dose of no, low- (3 mg/kg body weight), or high- (30 mg/kg) dose LF 16-0687Ms. After 24 hours, the amount of brain swelling and hemispheric water content were determined. Low and high doses of LF 16-0687Ms significantly reduced brain swelling by 25% and 27%, respectively (p < 0.03). Hemispheric water content tended to be increased in the nontraumatized hemisphere.

In a subsequent series of 10 rats, cisternal cerebrospinal fluid (CSF) samples were collected to determine whether changes in substances associated with edema formation could clarify why LF 16-0687Ms increases water content. For this, the volume regulator amino acid taurine, the excitatory transmitter glutamate, and the adenosine triphosphate degradation products hypoxanthine and xanthine were measured. In CSF, the levels of taurine, hypoxanthine, and xanthine were significantly decreased following a single administration of LF 16-0687Ms (p < 0.005); the level of glutamate, however, was double that found in control animals (p < 0.05).

Conclusions. Using the present study design, a single administration of LF 16-0687Ms successfully reduced posttraumatic brain swelling. The decreased levels of taurine, hypoxanthine, and xanthine may reflect reduced posttraumatic brain edema, whereas the increased level of glutamate could account for the elevated water content observed in the nontraumatized hemisphere.

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Andreas W. Unterberg, Bruce J. Andersen, Geoff D. Clarke and Anthony Marmarou

✓ Clinical and experimental evidence suggests that head injury can cause alterations of cerebral energy metabolism. However, the etiology of this metabolic perturbation is not known. The objective of this study was to determine the effect of fluid-percussion trauma on cerebral energy metabolism. Seven ventilated, chloralose-anesthetized cats were subjected to a 3.2-atm fluid-percussion brain injury. Before and for 8 hours after trauma, continuous phosphorus-31 magnetic resonance spectrography was obtained to noninvasively monitor tissue pH, phosphocreatine (PCr), and inorganic phosphate (Pi) levels. Measurement of cerebral blood flow (CBF) by the radioactive microsphere technique and calculation of oxygen and glucose consumption (CMRO2 and CMRGl) were also performed before trauma as well as 30 minutes and 1,2,4, and 8 hours after trauma. The data showed a moderate decrease in tissue pH from 7.04 to 6.89 at 30 minutes following trauma with return to control levels by 3 hours posttrauma. During the 8-hour observation period, CBF, CMRO2, and CMRGl remained at control levels. Tissue PCr and Pi levels were also unchanged.

Fluid-percussion trauma at the 3.2-atm level in ventilated cats causes a moderate and transient decrease in tissue pH that returns to control levels after trauma. No other metabolic changes are seen later than 30 minutes posttrauma. This indicates that a mild metabolic disturbance occurs after trauma in the ventilated animal and quickly returns to normal.

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John F. Stover, Britta Schöning, Oliver W. Sakowitz, Christian Woiciechowsky and Andreas W. Unterberg

Object. Disturbance of calcium homeostasis contributes to evolving tissue damage and energetic impairment following traumatic brain injury (TBI). Calcium-mediated activation of calcineurin results in production of tissue-damaging nitric oxide and free oxygen radicals. Inhibition of calcineurin induced by the immunosuppressant tacrolimus (FK506) has been shown to reduce structural and functional damage after ischemia. The aims of the present study were to investigate time- and dose-dependent short-term antiedematous effects of tacrolimus following TBI.

Methods. A left temporoparietal contusion (controlled cortical impact injury [CCII]) was induced in 51 male Sprague—Dawley rats. Tacrolimus (1 or 3 mg/kg body weight) was administered by a single intraperitoneal injection at 5 minutes, 30 minutes, or 4 hours after CCII occurred. Control rats received physiological saline. Water contents of traumatized and nontraumatized hemispheres, as well as cerebrospinal fluid (CSF) levels of mediators reflecting tissue damage (the proinflammatory cytokines interleukin [IL]-6 and tumor necrosis factor [TNF]—α, the excitotoxin glutamate, and the adenosine triphosphate—degradation product hypoxanthine), were determined 24 hours after trauma.

Although CSF levels of IL-6 and TNFα were completely suppressed by tacrolimus at all time points and at both concentrations, CSF levels of glutamate and hypoxanthine, as well as edema formation, were only marginally influenced. Significant reduction of cerebral water content was confined to nontraumatized hemispheres. In addition, the higher dose of tacrolimus failed to exert significant antiedematous effects on traumatized hemispheres.

Conclusions. Under the present study design, the potency of tacrolimus in reducing edema formation following CCII seems limited. However, its immunosuppressive effects could be of value in influencing the posttraumatic inflammatory response known to aggravate tissue damage.

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Andreas W. Unterberg, Oliver W. Sakowitz, Asita S. Sarrafzadeh, Götz Benndorf and Wolfgang R. Lanksch

Object. Ischemia due to vasospasm is a feared complication in patients following aneurysmal subarachnoid hemorrhage (SAH). Cerebral online microdialysis monitoring may detect the metabolic changes in the extracellular fluid associated with ischemia. The aims of the present study were to correlate clinical course, microdialysis-recorded data, transcranial Doppler (TCD) ultrasonography findings, and angiographic findings in patients with SAH.

Methods. In 60 patients a microdialysis catheter was inserted into the brain parenchyma that is most likely to be affected by vasospasm directly after aneurysm clipping. Hourly analyses of glucose, pyruvate, lactate, and glutamate levels were performed using a bedside device. Blood-flow velocities were obtained using serial TCD measurements. Cerebral angiography was routinely performed on Day 7 after aneurysm clipping or earlier in cases of clinical deterioration (30 patients). In all patients the results of microdialysis monitoring, TCD ultrasonography, and angiography were correlated.

The mean duration of monitoring was 7.3 ± 2.5 days. In patients with acute ischemic neurological deficits (18 patients) immediate microdialysis-recorded alterations were observed if the probe was placed close to the malperfused region. In 13 of 15 patients with symptomatic vasospasm (delayed ischemic neurological deficit [DIND]), the microdialysis-recorded values revealed secondary deterioration. In terms of confirming DIND, microdialysis had the highest specificity (0.89, 95% confidence interval [CI] 0.78–1) compared with TCD ultrasonography (0.63, 95% CI 0.46–0.8) and angiography (0.53, 95% CI 0.35–0.7). For microdialysis, the positive likelihood ratio was 7.8, whereas this was significantly lower for TCD ultrasonography (1.7) and angiography (2.1).

Conclusions. Although angiography also demonstrates vessel narrowing in asymptomatic patients, online microdialysis reveals characteristic metabolic changes that occur during vasospasm. Thus, online microdialysis may be used to confirm the diagnosis of vasospasm.

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Asita Sarrafzadeh, Daniel Haux, Ingeborg Küchler, Wolfgang R. Lanksch and Andreas W. Unterberg

Object. The majority of patients with poor-grade subarachnoid hemorrhage (SAH), that is, World Federation of Neurosurgical Societies (WFNS) Grades IV and V, have high morbidity and mortality rates. The objective of this study was to investigate cerebral metabolism in patients with low-compared with high-grade SAH by using bedside microdialysis and to evaluate whether microdialysis parameters are of prognostic value for outcome in SAH.

Methods. A prospective investigation was conducted in 149 patients with SAH (mean age 50.9 ± 12.9 years); these patients were studied for 162 ± 84 hours (mean ± standard deviation). Lesions were classified as low-grade SAH (WFNS Grades I–III, 89 patients) and high-grade SAH (WFNS Grade IV or V, 60 patients). After approval by the local ethics committee and consent from the patient or next of kin, a microdialysis catheter was inserted into the vascular territory of the aneurysm after clip placement. The microdialysates were analyzed hourly for extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol. The 6- and 12-month outcomes according to the Glasgow Outcome Scale and functional disability according to the modified Rankin Scale were assessed.

In patients with high-grade SAH, cerebral metabolism was severely deranged compared with those who suffered low-grade SAH, with high levels (p < 0.05) of lactate, a high L/P ratio, high levels of glycerol, and, although not significant, of glutamate. Univariate analysis revealed a relationship among hyperglycemia on admission, Fisher grade, and 12-month outcome (p < 0.005). In a multivariate regression analysis performed in 131 patients, the authors identified four independent predictors of poor outcome at 12 months, in the following order of significance: WFNS grade, patient age, L/P ratio, and glutamate (p < 0.03).

Conclusions. Microdialysis parameters reflected the severity of SAH. The L/P ratio was the best metabolic independent prognostic marker of 12-month outcome. A better understanding of the causes of deranged cerebral metabolism may allow the discovery of therapeutic options to improve the prognosis, especially in patients with high-grade SAH, in the future.

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Karl L. Kiening, Andreas W. Unterberg, Tillman F. Bardt, Gerd-Helge Schneider and Wolfgang R. Lanksch

✓ Monitoring of cerebral oxygenation is considered to be of great importance in minimizing secondary hypoxic and ischemic brain damage following severe head injury. Although the threshold for cerebral hypoxia in jugular bulb oximetry (measurement of O2 saturation in the jugular vein (SjvO2)) is generally accepted to be 50% oxygen saturation, a comparable value in brain tissue PO2 (PtiO2) monitoring, a new method for direct assessment of PO2 in the cerebral white matter, has not yet been established. Hence, the purpose of this study was to compare brain PtiO2 with SjvO2 in severely head injured patients during phases of reduced cerebral perfusion pressure (CPP) to define a threshold in brain PtiO2 monitoring. In addition, the safety and data quality of both SjvO2 and brain PtiO2 monitoring were studied.

In 15 patients with severe head injuries, SjvO2 and brain PtiO2 were monitored simultaneously. For brain PtiO2 monitoring a polarographic microcatheter was inserted in the frontal cerebral white matter, whereas for SjvO2 measurements were obtained by using a fiberoptic catheter placed in the jugular bulb. Intracranial pressure was monitored by means of an intraparenchymal catheter. Mean arterial blood pressure, CPP, end-tidal CO2, and arterial oxygen saturation (pulse oximetry) were continuously recorded. All data were simultaneously stored and analyzed using a multimodal computer system. For specific analysis, phases of marked deterioration in systemic blood pressure and consecutive reductions in CPP were investigated.

There were no complications that could be attributed to the PtiO2 catheters, that is, no intracranial bleeding or infection. The “time of good data quality” was 95% in brain PtiO2 compared to 43% in SjvO2; PtiO2 monitoring could be performed twice as long as SjvO2 monitoring. During marked decreases in CPP, SjvO2 and brain PtiO2 correlated closely. A significant second-order regression curve of SjvO2 versus brain PtiO2 (p < 0.01) was plotted. At a threshold of 50% in SjvO2, brain PtiO2 was found to be within the range of 3 to 12 mm Hg, with a regression curve “best fit” value of 8.5 mm Hg. There was a close correlation between CPP and oxygenation parameters (PtiO2 and SjvO2) when CPP fell below a breakpoint of 60 mm Hg, suggesting intact cerebral autoregulation in most patients.

This study demonstrates that monitoring brain PtiO2 is a safe, reliable, and sensitive diagnostic method to follow cerebral oxygenation. In comparison to SjvO2, PtiO2 is more suitable for long-term monitoring. It can be used to minimize episodes of secondary cerebral maloxygenation after severe head injury and may, hopefully, improve the outcome in severely head injured patients.