Clinical characteristics and prognostic factors of adult patients with pilocytic astrocytoma.

INTRODUCTION: Pilocytic astrocytoma (PA) is the most common primary brain neoplasm in children and treated in curative intent with gross total resection (GTR). However, PA is rare in adults, resulting in limited knowledge on the natural clinical course. This study aimed to describe the clinical course and identify prognostic factors of adult patients with PA. METHODS: 46 patients ≥ 18 years at diagnosis of PA and neurosurgical resection or biopsy between 2000 and 2018 were identified from the Neuro-Biobank of the Medical University of Vienna. In two cases with differing histopathological diagnosis at recurrence, DNA methylation analysis was performed using Illumina Infinium HumanMethylation850 BeadChip (850 k) arrays and the Molecular Neuropathology classifier. Clinico-pathological features were correlated with patient outcomes. RESULTS: Median age at diagnosis was 32.5 years (range: 19-75) and median Ki67 proliferation index was 2.8% (0.5-13.4%). Tumor location significantly correlated with resectability (p < 0.001). Tumor progression or recurrence was observed in 9/46 (19.6%) patients after a median follow up time of 53.0 months (range 0.5-300). 5-year overall and progression-free survival rates were 85.3% and 70.0%, respectively. 2/9 (22.2%) patients presented with histological changes in the recurrent tumor specimen. In detail, methylation classification redefined the histological diagnosis to anaplastic astrocytoma with piloid features and glioma in one patient, each. Age > 40 and higher body mass index (BMI) were associated with impaired progression-free and overall survival (p < 0.05). CONCLUSIONS: Tumor recurrence or progression in adult PA patients was higher than the one reported in pediatric patients. Higher age and BMI were associated with impaired prognosis.

Magnetic resonance velocity mapping of 3D cerebrospinal fluid flow dynamics in hydrocephalus: preliminary results.

OBJECTIVES: To investigate the detectability of CSF flow alterations in the ventricular system of patients with hydrocephalus using time-resolved 3D MR velocity mapping. METHODS: MR velocity mapping was performed in 21 consecutive hydrocephalus patients and 21 age-matched volunteers using a 3D phase-contrast (PC) sequence. Velocity vectors and particle path lines were calculated for visualisation of flow dynamics. CSF flow was classified as "hypomotile flow" if it showed attenuated dynamics and as "hypermotile flow" if it showed increased dynamics compared with volunteers. Diagnostic efficacy was compared with routine 2D cine PC-MRI. RESULTS: Seven patients showed hypomotile CSF flow: six had non-communicating hydrocephalus due to aqueductal stenosis. One showed oscillating flow between the lateral ventricles after craniotomy for intracranial haemorrhage. Seven patients showed normal flow: six had hydrocephalus ex vacuo due to brain atrophy. One patient who underwent ventriculostomy 10 years ago showed a flow path through the opening. Seven patients showed hypermotile flow: three had normal pressure hydrocephalus, three had dementia, and in one the diagnosis remained unclear. The diagnostic efficacy of velocity mapping was significantly higher except for that of aqueductal stenosis. CONCLUSIONS: Our approach may be useful for diagnosis, therapy planning, and follow-up of different kinds of hydrocephalus.

[Ethical aspects of dealing with coma patients]. / Ethische Aspekte im Umgang mit Komapatienten.

The number of patients who survive severe brain injury increased due to progress in neurosurgery and intensive care. To establish a proper prognosis on the coma stage and the possible potential of remission is difficult in many cases. The treatment of patients in chronic coma leads to economic and ethical problems. Progress in functional radiology may help to obtain a proper prognosis in future. While numerous issues deal with ethical aspects in case of brain death only few do so with treatment decisions in chronic coma patients.

Prognostic relevance of p53 protein expression in glioblastoma.

TP53 plays a key role in cellular response to DNA-damaging agents, and mutation of this gene, which is associated with immunohistochemically detectable p53 protein accumulation, may influence response to chemo- and radiotherapy. We investigated immunohistochemically the influence of p53 protein accumulation in 114 consecutive cases of primary glioblastoma treated by surgery and adjuvant radio- and chemotherapy. In addition, we determined cellular proliferation index using the antibody MIB-1 and apoptotic index of tumor cells using the TUNEL-assay. Twenty-nine patients (25.4%) were considered as positive with regard to p53 protein expression (>50% p53 immunostained tumor cells). Patients with p53 positive glioblastomas were significantly younger (mean age 54.4+/-2 years) than those with p53 negative tumors (mean age 61.4+/-1.1 years) (p=0.002, Mann-Whitney test). While no significant difference in apoptotic index was found, we observed a significantly higher MIB-1 labeling index (LI) in patients with p53 positive tumors (median LI: 36.4%) compared to p53 negative ones (median LI: 23.8%) (p=0.005, Mann-Whitney test). p53 protein expression was associated with significantly longer survival in univariate analysis (p=0.0399, log-rank test). In multivariate analysis of overall survival (Cox regression) only postoperative Karnofsky performance status remained as independent prognostic factor. We conclude that glioblastoma patients with immunohistochemically detectable p53 protein expression, who received adjuvant radio- and chemotherapy, have a significantly better overall survival, possibly due to increased sensitivity to this adjuvant treatment.

Social and economic outcome after posterior microforaminotomy for cervical spondylotic radiculopathy.

Between 1993 and 1998, the surgical technique of posterior cervical foraminotomy as described by Frykholm, with individual cervical nerve root decompression had been applied at the Neurosurgical Department of the University of Vienna. We conducted a retrospective study to assess the functional and socio-economic outcome. Thirty-two patients were included in this study, 21 men and 11 women with a median age of 48 years (range 30 to 70 years). Prior to surgical management, median duration of symptoms had been 7 weeks (range 1-50 weeks), with cervicobrachialgia in 28 of the patients, 27 of the patients had sustained radicular sensory loss, and in 25 of the patients radicular paresis occurred. Measured by the Prolo Functional Economic Outcome Rating Scale, 64% of the patients were classified with a good outcome (scale 8-10), 18% of the patients were classified with a moderate outcome (scale 5-7), and 18% of the patients were classified with a poor outcome (scale < 5). Two of the patients required additional anterior cervical discectomy and one patient suffered a superficial wound infection which needed surgical drainage. This study confirms that posterior microforaminotomy is a useful technique for degenerative disease causing cervical radiculopathy with the advantage of avoiding fusion and immobilisation. Criteria for evaluating the results of treating cervical spinal disorders vary widely. Comparative analyses of outcome among different therapy protocols are compromised by the diversity among the groups studied, as well as by the varying methods of measuring success. We propose a scale based on the socio-economic and functional status of the patient before and after treatment This scale is easily applicable and can delineate pre- and postoperative conditions of patients. A more universal acceptance of common criteria for judging the outcome of spinal operations should facilitate comparisons among various methods of treatment.

Survival improvement in patients with glioblastoma multiforme during the last 20 years in a single tertiary-care center.

METHODOLOGY: The survival of 357 consecutive patients with newly diagnosed glioblastoma multiforme (GBM) in three treatment groups reflecting different time-periods of diagnosis (A: 1982-1984; B: 1994/1995; C: 1996-1998) was analysed to assess the impact and the potential improvement of changing treatment strategies in our tertiary-care center. PATIENTS AND METHODS: Group A (n = 100) included all consecutive patients diagnosed from 1982 to 1984 and served as the historical control. Group B (n = 93) included all consecutive patients diagnosed in 1994/1995 and group C (n = 164) those diagnosed from 1996 to 1998. Survival in the three treatment groups (A vs. B vs. C) was analysed according to treatment given after neurosurgical intervention (i.e. no specific therapy versus radiotherapy versus combined radio-/chemotherapy), and according to first-line chemotherapy, age (< 40, 40-60, > 60), sex, and tumor location (hemispheric versus bilateral or multifocal tumors, and tumors involving eloquent brain areas). Survival was analysed using Kaplan-Meier's non-parametric method. A p-value < 0.05 was considered statistically significant. RESULTS: Patients in groups A and B received radio- and/or chemotherapy to a varying extent (radiotherapy: group A: 22%, group B: 62%; chemotherapy: group A: 6%, group B: 33%). Chemotherapy was administered after termination of radiotherapy in both groups. In group C, 96% of patients received combined radio-/chemotherapy which was administered concomitantly and started within three weeks after surgery. Median survival was 5.2 months in group A, 5.1 months in group B and 14.5 months in C (p < 0.0001). Nine patients in group A (9%), 9 in group B (10%) and 40 in group C (25%) survived more than 18 months (p < 0.05). CONCLUSIONS: Survival improvement in group C might be attributable to the early start of combined radio-/chemotherapy. Therapy was administered on a complete outpatient basis, enabled by a dedicated interdisciplinary neuro-oncologic team caring for group C. Toxicity was mild and patients' acceptance excellent.

The keyhole concept in aneurysm surgery: results of the past 20 years.

BACKGROUND: Improvements in preoperative imaging and intraoperative visualization have led to a refinement in surgical techniques. OBJECTIVE: Report of a 20-year experience with application of the keyhole technique as a contribution to the ongoing debate on the impact of limited craniotomies in aneurysm surgery. METHODS: Over a 20-year period, 1000 consecutive patients with 1297 aneurysms were surgically treated in 1062 operations: 651 in the acute stage after SAH and 411 with unruptured aneurysms. The outcome was assessed with the modified Rankin scale and approach-related complications. RESULTS: The majority of the cases were treated by 4 different keyhole approaches: The supraorbital approach was used in 793 patients for 989 aneurysms, the subtemporal in 48 patients for 50 aneurysms, the interhemispheric in 46 patients for 51 aneurysms, and the retromastoidal in 55 patients for 55 aneurysms. In 120 patients, the classic pterional approach was applied to treat 152 aneurysms. The results of unruptured aneurysms were good (modified Rankin scale ≤ 2) in 96.52%. The complication rates of the keyhole approaches were less than in the pterional group, although the difference did not reach statistical significance. CONCLUSION: The overall outcome, rate of retreatment, and approach-related complications with keyhole approaches for the management of ruptured and unruptured aneurysms are comparable to recently published conventional surgical aneurysm series. In addition to the common benefits of limited-exposure approaches, this series demonstrates appropriate safety and applicability of the keyhole technique in aneurysm surgery.

Physiotherapy-based rehabilitation following disc herniation operation: results of a randomized clinical trial.

STUDY DESIGN: Three-group, randomized, single blinded, controlled trial. OBJECTIVE: To test the effectiveness of physiotherapy-based rehabilitation starting 1 week after lumbar disc surgery. In addition, we tried to estimate the contribution of specific effects to the observed outcome (efficacy). SUMMARY OF BACKGROUND DATA: Physiotherapy-based rehabilitation is usually recommended for patients following lumbar disc surgery. Few and conflicting data exist for the relative effectiveness of this intervention. METHODS: A total of 120 patients following first-time, uncomplicated lumbar disc surgery were randomly assigned to "comprehensive" physiotherapy, "sham" neck massage, or no therapy. Before enrollment, all subjects completed a minimal physiotherapeutic intervention. Physiotherapy was administered by experienced physiotherapists and consisted of 20 sessions per patient over 12 weeks. Masseurs administered "sham massage" to the neck. The amount of treatment time was equal to that of physiotherapy. The main outcome measure was the Low Back Pain Rating Score (LBPRS) at 6 and 12 weeks, and 1.5 years after randomization. Secondary parameters were patients' overall satisfaction with treatment outcome and socioeconomic and psychologic measures. RESULTS: At the end of therapy (12 weeks), the LBPRS revealed a significantly better improvement in the physiotherapy group than in the untreated group. LBPRS outcome, however, did not significantly differ between physiotherapy and "sham" therapy. There was a tendency toward significance between the sham therapy and no therapy. Within the 1.5-year follow-up, LBP rating scales remained significantly improved compared with baseline, but there were no significant outcome differences. No statistically significant between-group differences were found for the secondary outcome parameters. CONCLUSION: As compared with no therapy, physiotherapy following first-time disc herniation operation is effective in the short-term. Because of the limited benefits of physiotherapy relative to "sham" therapy, it is open to question whether this treatment acts primarily physiologically in patients following first-time lumbar disc surgery, but psychological factors may contribute substantially to the benefits observed.

Microsurgical treatment of juxta facet cysts of the lumbar spine.

OBJECTIVES: Juxta facet cysts are a common cause of low back and radicular pain. They are mostly associated with degenerative facet joints and spondylolisthesis. The study focuses on long-term outcomes after microsurgical treatment without fusion. METHOD: From April 2002 to April 2004, 31 patients (23 female and 8 male) underwent microsurgical resection of lumbar juxta facet cysts. The patient age ranged from 31 to 83 years (mean 67.2 years). The most affected level was L4-L5 (19 patients), followed by L3-L4 (9 patients). Fourteen patients additionally had spondylolisthesis of the involved segment. All patients had signs of nerve root compression and had received conservative treatment preoperatively. We performed limited bone removal (sparing the facet joints) and cyst resection in 27 patients. In four patients, cyst resection and standard laminectomy were performed owing to spinal stenosis. RESULTS: Conservative treatment was without any effect in all patients. At follow-up, 12-30 months after surgery, excellent to good outcome was achieved in 25 of 31 patients (80.7%), and 6 patients (19.3%) showed fair results. Persistent low back pain was more common in patients with spondylolisthesis than in the other group (6/14 vs 3/17); this may be due to instability. Spondylolisthesis did not progress or become mobile after surgery radiographically in any of our patients. CONCLUSIONS: Conservative therapy does not adequately improve symptoms in patients with intraspinal juxta facet cysts and radicular signs. Juxta facet cysts can be treated effectively with a minimally invasive microsurgical approach. This may be of particular significance when the cysts are associated with spondylolisthesis, minimizing the risk of instability and the need for fusion. In a selected group of patients with persistent low back pain, fusion may become necessary to improve symptoms.

Intraoperative evaluation of implants in anterior cervical spine surgery by three-dimensional fluoroscopy.

OBJECTIVE: Accurate radiographic documentation of the proper placement of cages, plates, and screws following cervical spine surgery significantly impacts clinical outcome. Postoperative computed tomography scans clearly show that the position of implants is sometimes far from ideal. The morbidity of anterior cervical disc surgery is well documented, but the incidence and influence of the misplacement of interbody spacers, plates, and screws are underestimated. We used isocentered fluoroscopy with three-dimensional image reconstruction intraoperatively to evaluate the extent of bony decompression and position of implants before wound closure. METHODS: From October 2003 through April 2004, 27 patients had anterior cervical procedures: 22 one-level and 5 two-level operations. Herniated cervical discs were diagnosed in 21 individuals, whereas 6 exhibited spondylosis. A radiolucent operating table made of carbon fibers was used in all patients. Before wound closure, intraoperative three-dimensional fluoroscopy was performed to evaluate the location of cervical implants and anterior bone resection. RESULTS: The entire scanning procedure required 5 minutes; the actual scanning time was only 120 seconds. In all patients, we were able to adequately evaluate the placement of cage, plates, and screws. Utilization of intraoperative three-dimensional fluoroscopy revealed that two cages were malpositioned and required revision before wound closure. CONCLUSIONS: Intraoperative three-dimensional fluoroscopy is a valuable tool for the intraoperative imaging of bony decompression and implants in anterior cervical spine surgery. The technique is safe and reliable and should help us to avoid incomplete decompression or misplacement of implants and therefore improve long-term functional outcomes in the future.

Survival and prognostic factors of patients with unresectable glioblastoma multiforme.

The aim of this study was to assess survival and prognostic factors of 98 consecutive patients with unresectable glioblastoma multiforme (GBM) after stereotactic biopsy. Patients were diagnosed between 1993 and 1998, and the treatment modality subsequent to stereotactic biopsy was determined by the year of diagnosis. Before 1995, patients did not receive further specific therapy after stereotactic biopsy (n=36). In 1996, patients were administered radiotherapy starting within 6 weeks after stereotactic biopsy (n=24). From 1997 to 1998, patients received combined radio-/chemotherapy (RCT; CCNU orally) starting within 2 weeks after stereotactic biopsy (n=38). Patients' age ranged from 21 to 84 (median 64) years and their median Karnofsky performance score 2 weeks after stereotactic biopsy was 80 (range 60-100). Survival and prognostic factors were analyzed with respect to administered treatment modalities (without specific therapy versus radiotherapy versus combined RCT), with respect to age (>oror=or<80), tumor location (frontal, parieto-temporal, central, occipital) and tumor size (>or5 cm) by the Kaplan-Meier method, by log-rank test and multivariate Cox regression analysis. Post-biopsy treatment modality was the strongest predictor for survival. Median (range) survival was 9 (3-47) weeks in those without specific therapy, 13 (5-54) weeks in patients receiving radiotherapy and 31 (11-101) weeks in patients receiving combined RCT (p

Second-line chemotherapy with dacarbazine and fotemustine in nitrosourea-pretreated patients with recurrent glioblastoma multiforme.

The aim of this study was to assess the efficacy and toxicity of a combination of dacarbazine (D) and fotemustine (F) administered to a homogenous group of patients with recurrent or progressive glioblastoma multiforme (GBM). Thirty-one patients with computed tomography or magnetic resonance imaging scan evidence of recurrent or progressive GBM after first-line chemotherapy with nitrosoureas as well as radiation therapy were given a combination of D (200 mg/m2) and F (100 mg/m2). At 30 min after termination of D administration, F was given over 60 min. Treatment was performed in an outpatient setting every 21 days. A total of 140 cycles (range 1-12 cycles; median 4 cycles) was administered. One partial response (3%) lasting for 11 weeks was observed. Sixteen (52%) patients reached stable disease lasting between 7 and 94 weeks. Median survival from start of the D/F combination was 45 (range 10-150) weeks. Median time to progression was 17 (3-101) weeks for all patients. Major toxicity was myelosuppression resulting in exclusion from study in seven (23%) patients [due to thrombocytopenia common toxicity criteria (CTC) grade 2 persisting longer than 3 weeks in three patients, due to thrombocytopenia CTC grade >/=3 in three and due to leukopenia CTC grade 3 in one patient]. No other toxicity than alopecia occurred. We conclude that the D/F combination is a well-tolerated second-line regimen and can be administered in a complete outpatient setting. D/F shows efficacy even in nitrosourea-pretreated patients and justifies further investigation.

Feasibility and toxicity of CCNU therapy in elderly patients with glioblastoma multiforme.

In our institution, 103 glioblastoma multiforme (GBM) patients aged from 55 to 83 years were treated since November 1994 as follows. All patients underwent surgical intervention (gross total resection, n = 35; subtotal resection, n = 38; stereotactic biopsy, n = 30). Subsequently all patients were offered radiotherapy and chemotherapy with CCNU. Results were as follows: 101 patients started radiotherapy, 93 patients completed it (96% of the patients aged < 65 years and 85% of the patients > or =65 years). All patients received at least 1 cycle of chemotherapy (median 3 cycles). Chemotherapy-associated toxicity was generally mild, more pronounced in females and did not increase with age. Median time to progression was 10.5+/-3.2 months for the patients < 65 years and 5.1+/-1 months for patients > or =65 years. median overall survival was 17.5+/-3.8 months in patients < 65 years and 8.6+/-1 months in patients > or =65 years (p < 0.0001). In multivariate analysis, age and female sex remained independent prognostic factors. Our data indicate that a treatment concept including concomitant radio- and chemotherapy is feasible even in elderly patients with GBM.