J. R. Moringlane

Detection and Quantification of Vascular Endothelial Growth Factor/Vascular Permeability Factor in Brain Tumor Tissue and Cyst Fluid

In primary malignant brain tumors increased vascularity and marked edema strongly suggest a possible role of the vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). This was confirmed by earlier in situ hybridization studies, by analysis of the expression of the mitogen in different subsets of glioblastoma cells, and by the fact that the VEGF/VPF receptor flt-1 (fms-like tyrosine kinase) is up-regulated in tumor cells in vivo. To assess and quantify the expression of the VEGF/VPF gene and of the receptor gene, 26 surgical specimens of brain tumor tissue from 24 patients were analyzed. In most malignant gliomas, the expression level of the VEGF/VPF gene is elevated and can be increased up to 20- to 50-fold in comparison with low-grade tumors. Using polymerase chain reaction-based amplification, it could be shown that the messenger RNAs of three different VEGF/VPF forms are synthesized in tumor tissue samples. Northern blot studies revealed that in some samples a significant expression of the gene coding for placenta growth factor, a growth factor closely related to VEGF/VPF, was observed. In addition, using a radioreceptor assay it was possible to detect high VEGF/VPF-like activity in the cyst fluids of brain tumors, indicating the accumulation of the mitogen and permeability factor in brain tumor cysts. Further investigations revealed that astrocytoma and glioblastoma cells in culture express the VEGF/VPF gene and secrete the VEGF/VPF protein, whereas gene expression of the two known VEGF/VPF receptors, kinase insert domain-containing receptor and flt-1, could not be detected. These data support previous reports, which stated that VEGF/VPF acts as a paracrine growth and permeability factor in brain tumors and may contribute to tumor growth by initiating tumor angiogenesis.

Thermocoagulation of the dorsal root entry zone for the treatment of intractable pain.

The authors report the results of DREZ thermocoagulation in 35 patients since March 1980. This technique was applied not only in patients with deafferentation pain after brachial plexus avulsion, but also for postamputation phantom limb pain and pain caused by injury to the spine and spinal cord, by peripheral nerve lesions, and by multiple sclerosis. Independent of etiology, the duration of the pain syndrome, and the quality and projection of the pain, the overall results have been satisfactory and long-lasting.

Clinical Value of Iodine-123-Alpha-Methyl-l-Tyrosine Single-Photon Emission Tomography in the Differential Diagnosis of Recurrent Brain Tumor in Patients Pretreated for Glioma at Follow-Up

PURPOSE To assess the clinical potential of iodine-123-alpha-methyl-L-tyrosine (IMT) and single-photon emission tomography (SPET) in the differential diagnosis of recurrences in patients pretreated for gliomas at follow-up. PATIENTS AND METHODS Seventy-eight patients were examined after primary therapy over 36 months. Histopathologic diagnoses of all patients was known at first treatment; magnetic resonance and/or computed tomography examination was performed in addition to IMT-SPET. Cerebral SPET images were acquired 20 minutes after intravenous application of 190 +/- 10 MBq of IMT. SPET images were classified as positive or negative for recurrent tumor visually and by calculating the ratios between tracer accumulation in the lesion and the unaffected contralateral regions of reference using region of interest. Final diagnoses were based on prospective clinicopathologic findings obtained independently of IMT-SPET. RESULTS IMT-SPET detected all high-grade recurrent gliomas (grade 4; sensitivity, 100%). A difference could be demonstrated in grade 2 and 3 recurrences (sensitivity, 84% and 92%, respectively). Moreover, benign posttherapeutic lesions (postoperative scars, radiation necrosis) were correctly diagnosed as negative for tumor recurrence. In general, IMT uptake in grade 2 (1.45 +/- 0.24) was significantly lower than that in grades 3 (1.70 +/- 0.41) and 4 (1.88 +/- 0.32). However, it was difficult to evaluate tumor grade only from the IMT accumulation in individual cases. CONCLUSION IMT-SPET seems highly useful for detecting and delineating recurrent gliomas and differentiating between benign posttherapeutic lesions and malignant tumor tissue. It may be a valuable clinical tool to diagnose recurrences in patients pretreated for gliomas at follow-up. However, it showed limitations in determining histologic tumor grade.

Ultrasound-based navigation during intracranial burr hole procedures: experience in a series of 100 cases.

BACKGROUND To establish a rational basis for intraoperative ultrasound guidance in neurosurgical procedures via a single burr hole approach based on the experience of one hundred cases. METHODS The single burr hole approach is carried out using a bayonet-shaped ultrasound transducer with a tip dimension of 8 x 8 mm. The ultrasound probe with a mounted puncture adapter fits a standard burr hole and allows real-time imaging of the ongoing surgical steps. RESULTS One hundred cases with five indications have been operated on so far: tapping of the ventricular system (46 patients), tapping of intracranial cysts (23 patients), biopsy of intracranial tumors (15 patients), evacuation of intracranial abscesses (9 patients), and evacuation of intracerebral hematomas (7 patients). Depending on their size, the ventricles could be clearly visualized in 34 of 46 patients. In the remaining patients the free margin of the falx served as orientation. Two ventricles could neither be visualized nor entered. Visualization and puncture of intracranial cysts were easy to achieve throughout, as was the case with abscesses. Tumor biopsy was unsuccessful in two patients harboring lymphomas at distances of more than 50 mm from probe to target. Intracerebral hematomas were easily visualized but, due to the presence of clots, aspiration was impossible in two patients. One patient with a giant glioblastoma died the day after the uneventful biopsy due to increased cerebral edema. No other complications occurred. CONCLUSIONS The presented method of ultrasound-based neuronavigation is an easy-to-use, fast, and safe technique of real-time imaging for free-hand single burr hole procedures.

Experimental Radiofrequency (RF) Coagulation with Computer-based on Line Monitoring of Temperature and Power*

SummaryThe safety and reliability of radiofrequency coagulative techniques are questioned after each coagulation, especially in functional neurosurgery. In spite of the high level of technical development of modern surgical RF generators there is still uncertainty about the character of the coagulative lesion.For the present study, a 500 kHz RF generator was connected through a module for analog/digital conversion and for regulation to a personal computer provided with a software programme for the graphic display in real time of the RF power and of the temperature/time curves. The effects of thermocoagulation were studied in fresh egg white, and monopolar lesions were made in the subcortical white matter of rabbits with a probe with a 0.5 mm diameter and a bare tip of 3 mm in length. The regularity of thermocoagulation depends on the accurate temperature reading at the tip of the electrode. The ideal course of the temperature is a smoothly ascending curve from the level of 37 °C to the level present for coagulation, followed by a straight horizontal line. With too slow a response of the probe to temperature changes there is an inherent danger of overheating in the initial phase of the procedure. Additionally the power level has to be adjusted for each probe.On line monitoring with graphic display of the physical parameters provides a direct control of the course of the coagulation. Regular curves of the physical parameters without temperature overshoot correspond to reproducible lesionsin vitro andin vivo.

Colloid Cysts of the Third Ventricle: Open operative approach or stereotactic aspiration?

Colloid cysts of the third ventricle can cause hydrocephalus if they grow to the point where they occlude the foramina interventricularia. The operative approach via a craniotomy used to be the common method of treating these lesions. Now, in the era of CT- and MR-scanning, stereotactic aspiration should be preferred as an ideal method of simultaneously diagnosing and treating colloid cysts. Unlike open surgery, aspiration of colloid masses poses hardly any risk for the patient. Ten cases successfully treated by this technique are presented.

Cavum vergae cyst as a cause of hydrocephalus, “Almost Forgotten”?

SummaryCavum vergae cysts (CVC) are cerebral midline malformations, which usually have no clinical manifestations. In rare cases, however, non-communicating cysts can cause hydrocephalus by obstruction of the aqueduct. Initially, from 1930 to 1960 operative treatment consisted in open cysto-ventriculostomy,i.e. establishing a communication between CVC and the ventricles, via a transventricular approach. In the era of CT, symptomatic treatment of the hydrocephalus by ventriculo-atrial or ventriculo-peritoneal sunts is preferred. All the wellknown complications of shunting are encountered. Based on the experience of our cases of CVC with clinical manifestations, we here propose a definitive causal treatment which can be achieved by draining the cyst contents into the ventricles via a stereotactically introduced catheter.

Distribution of Epidermal Growth Factor Receptor Protein Correlates with Gain in Chromosome 7 Revealed by Comparative Genomic Hybridization after Microdissection in Glioblastoma Multiforme

In a recent study, 23 microdissected areas of 10 glioblastoma multiforme (GBM) were investigated for quantitative genomic aberrations using comparative genomic hybridization (CGH). To validate the chromosomal aberrations, as revealed by CGH after microdissection, parallel tissue sections were stained immunohistochemically with an antibody that detects both wild-type epidermal growth factor receptor (EGFR) and the deletion mutant form of the receptor (EGFRvIII). Immunostaining was correlated with CGH data of chromosome 7, because chromosome 7 is the most frequently aberrant chromosome in GBM (here four of 10 tumors), and this aberration often indicates an abnormality of EGFR. Nine of nine areas that showed gain in or amplification (2 areas) of chromosome 7 with CGH contained EGFR-immunoreactive cells. Only three of 14 areas without abnormality of chromosome 7 in CGH contained EGFR-immunoreactive cells; eleven of 14 areas were immunonegative. Our findings demonstrate a strong correlation between immunohistochemistry of EGFR and the copy numbers of chromosome 7, as revealed by CGH after microdissection in glioblastoma multiforme.

Intra-individual comparison of p-[123I]-iodo-L-phenylalanine and L-3-[123I]-iodo-α-methyl-tyrosine for SPECT imaging of gliomas

ObjectivesRadioactive amino-acids accumulate in gliomas even with an intact blood-brain-barrier. L-3-[123I]-iodo-α-methyl-tyrosine (IMT) is well established for SPECT imaging of gliomas. Recently, we introduced p-[123I]-iodo-L-phenylalanine (IPA) for the characterisation of brain lesions. This study compares both tracers in glioma patients.MethodsEleven patients with gliomas (1 WHO grade 1, 5 grade 2, 1 grade 3, 2 grade 4 gliomas, 1 unconfirmed upgrading and 1 post-therapeutic non-neoplastic lesion) underwent SPECT imaging with IPA (early and delayed acquisitions at 30 min and 3 h) and IMT (early only). Maximum tumour-to-brain ratios (TBR) were calculated using region-of-interest analysis to assess uptake of IMT and IPA. Imaging results were compared to histopathological findings.ResultsEarly TBRs of IMT and IPA were strongly correlated (r = 0.828, p = 0.002). TBRs were higher for IMT than IPA (1.95±0.50 versus 1.79±0.42; p < 0.05), but independent from tumour cell density (p > 0.1). Visual interpretation by different observers was more concordant for IMT-SPECT than IPA-SPECT (kappa 1.0 versus 0.774). No differences in early TBRs were observed between low-grade and high-grade gliomas for IMT (1.97±0.53 versus 2.21±0.44, p > 0.5) or IPA (1.70±0.23 versus 2.21±0.56, p = 0.167) with a trend to higher TBRs in low-grade tumours for IMT (p = 0.093). In contrast to the known wash-out of IMT, we observed persistent accumulation of IPA in gliomas.ConclusionsIPA shows lower TBRs than IMT, especially in low-grade tumours, so IMT should be preferred for the delineation of low-grade gliomas by SPECT imaging. Due to its prolonged retention, however, IPA remains promising for therapeutic use in gliomas after labelling with I-131.

Polysyndactyly and asymptomatic hypothalamic hamartoma in mother and son : a variant of Pallister-Hall syndrome

We report on a 53‐year‐old woman and her 20‐year‐old son who both presented with polysyndactyly, without other external malformations or mental retardation. MRI imaging revealed, as an incidental finding, asymptomatic hypothalamic hamartomas in both patients. The siblings of both mother and son are unaffected. This family may represent an autosomal dominant variant of Pallister‐Hall syndrome.