Gross-total resection of malignant gliomas in elderly patients: implications in survival.

BACKGROUND: Malignant gliomas in elderly patients are frequently under represented in neuro-oncology trials because of presumed low tolerability of gross-total resection and radiochemotherapy treatments. Thus, the balance of benefit versus adverse response of standard glioma therapy remains controversial. We hypothesized that older patients with malignant gliomas might also take advantage of extensive surgical procedures. PATIENTS AND METHODS: We analyzed retrospectively 138 consecutive malignant glioma patients. Sixty-two patients were >65 years whereas seventy-six were

Enhancing accuracy of magnetic resonance image fusion by defining a volume of interest.

We compared the registration accuracy for corresponding anatomical landmarks in two MR images after fusing the complete volume (CV) and a defined volume of interest (VOI) of both MRI data sets. We carried out contrast-enhanced T1-weighted gradient-echo and T2-weighted fast spin-echo MRI (matrix 256 x 256) in 39 cases. The CV and a defined VOI data set were each fused using prototype software. We measured and analysed the distance between 25 anatomical landmarks in predefined areas identified at levels L(1)-L(5) corresponding to defined axial sections. Fusion technique, landmark areas and level of fusion were further processed using a feed-forward neural network to calculate the difference which can be expected based on the measurements. We identified 975 landmarks for both T1- and T2-weighted images and found a significant difference in registration accuracy ( P<0.01) for all landmarks between CV (1.6+/-1.2 mm) and VOI (0.7+/-1.0 mm). From cranial (L(1)) to caudal (L(5)), mean deviations were: L(1) CV 1.5 mm, VOI 0.5 mm; L(2) CV 1.8 mm, VOI 0.4 mm; L(3) CV 1.7 mm, VOI 0.4 mm; L(4) CV 1.6 mm, VOI 0.6 mm; and L(5) CV 1.6 mm, VOI 1.6 mm. Neural network analysis predicted a higher accuracy for VOI (0.05-0.15 mm) than for CV fusion (0.9-1.6 mm). Deviations due to magnetic susceptibility changes between air and tissue seen on gradient-echo images can decrease fusion accuracy. Our VOI fusion technique improves image fusion accuracy to <0.5 mm by excluding areas with marked susceptibility changes.

The translaminar approach to canalicular and cranio-dorsolateral lumbar disc herniations.

INTRODUCTION: The interlaminar approach is the standard procedure for most disc herniations in lumbar spine surgery. However, in cranially extruded disc herniations including canalicular herniations, partial or complete facetectomy is necessary with increased risk of postoperative spinal instability. We present the translaminar technique which allows a more direct and less destructive operative approach. METHODS: 30 patients using the translaminar fenestration were analysed by a postoperative follow-up of 6 weeks and one year. The mean-age was 57.2 years. For resection of the disc herniation, a small round or oval fenestration (6-8 mm) in the hemilamina, craniomedially to the facet joint, was performed. No patient received a partial or total facetectomy. RESULTS: The majority of affected discs were at the L4-L5 level (53%). An extruded fragment was found in 28 patients (93%). In 5 patients bleeding from epidural veins complicated the intra-operative course. In 50% the nerve root was visually exposed. 15 patients (50%) had an intervertebral discectomy additional to the fragment excision. One patient was re-operated on after 10 days because of persisting radicular pain by using the same translaminar approach. 28 patients showed complete or nearly complete relief of radicular pain. Using this approach we have seen no major complication or clinical instability during a follow-up of at least one year. CONCLUSIONS: The translaminar approach is an effective and minimally invasive technique in both canalicular and cranio-dorsolateral disc herniations. It gives an additional possibility to avoid partial removal of the facet joints, can be performed in all lumbar segments and preserves structures important for segmental spinal stability. The approach allows access to the extruded disc fragment and intervertebral disc space comparable to classical approaches and is a frequently used operative technique in our department.

Evoked potentials in acute head injured patients with MRI-detected intracerebral lesions.

BACKGROUND: Magnetic resonance imaging (MRI) allows precise detection of intracranial lesions in head injured patients. We compared intracranial lesions detected in MRI to somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) concerning their prognostic value. METHODS: Thirty patients with traumatic brain injury and prolonged recovery were studied. Size, side and number of 474 intra- and extraparenchymal lesions as well as lesion localisation based on a specific anatomical classification were entered into a database (a total of 7080 data). In addition, we recorded median-nerve SEP (M-SEP), tibial nerve SEP (T-SEP) and BAEP in all of the patients. FINDINGS: M-SEP and Glasgow-Outcome-Score (GOS) one year after injury correlated significantly to patients with lesions in the brainstem (p<0.0001) and corpus callosum (p<0.001). Similar results were found for T-SEP (p<0.0001). All patients with bicortical loss of M-SEP had an unfavourable outcome (GOS 2). Among the analysis of lesion volume, only the volume of brainstem lesions correlated to GOS (p<0.001), but this was not found for callosal lesions. However, comparing the vegetative (GOS 2) to the non-vegetative group (GOS 3-5), for both callosal (p<0.02) and brainstem (p<0.005) lesions a significant correlation was found. INTERPRETATION: MRI does not improve the prognostic reliability of SEP in head injury but offers possibilities for clarifying electrophysiological and clinical pathologies. This explains that the volume of brainstem lesions, essentially influencing the clinical outcome, is strongly correlated to T-SEP and M-SEP. In contrast, callosal lesions did not show a clear relationship to outcome despite large callosal lesions (>4 ml) which tended to poor outcome. In conclusion, we suggest that MRI and SEP are supplementary to each other concerning prognostic evaluation.

Effect of 1-methyl-4-phenylpyridinium on glutathione in rat pheochromocytoma PC 12 cells.

We investigated the effect of the selective dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) on glutathione redox status and the generation of reactive oxygen intermediates (ROI) in rat pheochromocytoma PC 12 cells in vitro. Treatment with MPP+ (250 microM) led to a 63% increase of reduced glutathione (GSH) after 24 h, while a 10-fold higher concentration of MPP+ (2.5 mM) depleted cellular GSH to 12.5% of control levels within that time. Similarly, the complex I-inhibitor rotenone induced a time-dependent loss of GSH at 1 and 10 microM, whereas treatment with lower concentrations of rotenone (0.1, 0.01 microM) increased cellular GSH. Both MPP+ and rotenone increased cellular levels of oxidised glutathione (GSSG) and the higher concentrations of both compounds led to an elevated ratio of oxidised glutathione (GSSG) vs total glutathione (GSH + GSSG) indicating a shift in cellular redox balance. MPP+ or rotenone did not induce the generation of ROI or significant elevation of intracellular levels of thiobabituric acid reactive substances (TBARS) for up to 48 h. Our data suggest that MPP+ has differential effects on glutathione homeostasis depending on the degree of complex I-inhibition and that inhibition of complex I is not sufficient to generate ROI in this paradigm.

Effect of intracerebral lesions detected in early MRI on outcome after acute brain injury.

In the present study we classified intracerebral lesions likely to influence the outcome of head injured patients according to localization, lesion type, lesion number and lesion volume. A score of intracerebral lesions based on findings in early MRI is presented. Early MRI studies were performed in 30 patients (average 5-6 days after trauma) and outcome (GOS) was determined after 3 and 12 months. Lesions were classified and lesion volume V was calculated (V = pi abc/6). The applied intracerebral lesion score included lesions in the frontal cortex, basal ganglia, corpus callosum and brainstem. Patients in a persistent vegetative state (PVS) showed a higher number (p = 0.018) and volume (p = 0.013) of frontal lesions as compared to the non-vegetative group (NPVS). Lesion volume in basal ganglia differed significantly between PVS and NPVS (p = 0.01) and correlated to outcome (r = -0.65, p < 0.005). Volume difference in the corpus callosum between PVS and NPVS was significant (p = 0.02). The number (r = -0.61, p < 0.005) and volume (r = -0.62, p < 0.005) of brainstem lesions correlated to outcome and PVS differed in number (p = 0.012) and volume (p = 0.006). The intracerebral lesion score correlated to the GOS (r = -0.57, p = 0.001) and PVS and NPVS differed significantly. A lesion volume exceeding 40 ml in the frontal cortex, 3.5 ml in the basal ganglia, 4 ml in the corpus callosum or 1.5 ml in the brainstem is likely to lead to an unfavorable outcome. More than 4 lesions in the frontal cortex or 3 lesions in the brainstem appeared more frequent in patients with unfavorable outcome. Treatment strategies in the early phase after brain injury could be modified by the knowledge of certain lesions only visible on MRI.

MPP+ inhibits proliferation of PC12 cells by a p21(WAF1/Cip1)-dependent pathway and induces cell death in cells lacking p21(WAF1/Cip1).

The molecular and biochemical mode of cell death of dopaminergic neurons in Parkinson's disease (PD) is uncertain. In an attempt at further clarification we studied the effects of 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on dopaminergic PC12 cells. In humans and nonhuman primates MPTP/MPP+ causes a syndrome closely resembling PD. MPP+ toxicity is thought to be mediated by the block of complex I of the mitochondrial electron transport chain. Treatment of undifferentiated PC12 cells with MPP+ primarily inhibited proliferation of PC12 cells and secondarily led to cell death after the depletion of all energy substrates by glycolysis. This cell death showed no morphological characteristics of apoptosis and was not blocked by treatment with caspase inhibitors. The inhibition of cell growth was not dependent on an inhibition of complex I activity since MPP+ also inhibited cell proliferation in SH-SY5Y cells lacking mitochondrial DNA and complex I activity (p0 cells). As shown by flow cytometric analysis, MPP+ induced a block in the G0/G1 to S phase transition that correlated with increased expression of the cyclin-dependent kinase inhibitor p21(WAF1/Cip1) and growth arrest. Since treatment with 1 microM MPP+ caused apoptotic cell death in p21(WAF1/Cip1)-deficient (p21(-/-)) but not in parental (p21(+/+)) mouse embryo fibroblasts, our data suggest that in an early phase MPP+-induced p21(WAF1/Cip1) expression leads to growth arrest and prevents apoptosis until energy depletion finally leads to a nonapoptotic cell death.

Differential effects of L-buthionine sulfoximine and ethacrynic acid on glutathione levels and mitochondrial function in PC12 cells.

We investigated the effect of glutathione (GSH) depletion on mitochondrial function and generation of reactive oxygen intermediates (ROI) in PC12 cells in vitro. Direct depletion of cellular GSH using ethacrynic acid (EA, 500 mM) resulted in a concentration-dependent generation of ROI and cell death within 24 h. Treatment with 500 microM L-buthionine sulfoximine (BSO), which inhibits GSH synthesis, reduced cellular GSH but did not lead to generation of ROI. Furthermore, cells remained viable up to 72 h. Analysis of subcellular fractions revealed complete loss of cytosolic and mitochondrial GSH within 4 h of EA treatment. In contrast, BSO-treated cells still maintained 100% GSH in the mitochondrial fraction for 4 h and 6% for 48 h. Mitochondrial complex II/IIi and IV activities were not significantly decreased up to 48 h of BSO treatment while EA treatment resulted in a complete loss of complex II/III activity and a 70% reduction of complex IV activity within 4 h. These findings suggest that mitochondrial GSH is critical for the maintenance of mitochondrial function and cellular viability.