What is the value of emission tomography studies in patients with a primary glioblastoma multiforme treated by 192Ir brachytherapy?

BACKGROUND: We studied the use of (201)Thallium SPECT and L-[1-(11)C]-tyrosine PET in patients with a primary glioblastoma multiforme treated with (192)Ir brachytherapy after surgery and external beam radiation therapy. We hypothesised that the patients most likely to benefit from further surgery after deterioration would be those with radiation necrosis and would be recognised by a negative emission tomography scan. METHODS: Twenty-one patients underwent (201)Thallium SPECT performed before brachytherapy, and this was repeated in 19 patients when recurrence was suspected. Nine patients also underwent a PET scan at the same time. Nine patients underwent a second operation. FINDINGS: SPECT and PET were highly concordant concerning the prediction of radionecrosis and/or tumour recurrence. Repeat surgery did not lead to a significant increase in survival. There was no significant association between the duration of survival and tumour-to-background ratio but the number studied was small. Both SPECT and PET showed highly active lesions, which were proved to be recurrent tumour by clinical and histological follow-up. CONCLUSION: Although PET and SPECT are both highly sensitive in detecting active tumour tissue, emission tomography was not clinically valuable in the investigation of patients with a primary glioblastoma treated with brachytherapy.

Surgical considerations in movement disorders: deep brain stimulation, ablation and transplantation.

Surgical therapy for movement disorders has been practiced since the early 20th century, mostly for Parkinson's disease. At its onset, large destructive procedures like open resection of cortex, parts of the basal ganglia or its fibre connections produced variable, ill-documented results. With the introduction of the stereotactic operating technique in the second half of the century, ablative surgery became more refined, and more selective interventions became possible to alleviate the suffering of those patients for whom no other treatment modalities were yet available. However, the introduction of levodopa-based pharmacological therapy pushed surgical therapy almost completely to the background. In the past two decades, there has been a resurgence of interest in surgery for movement disorders, due to both limitations of long-term pharmacological therapy and the advent of the treatment modality of deep brain stimulation. The subject has now grown into a large field of clinical and scientific interest. Parkinson's disease is the most widespread surgical indication, but in other movement disorders considerable improvement can be achieved by surgery as well, most notably in dystonia. A short review of the surgical therapy for these disorders is presented.

Molecular characterization of areas with low grade tumor or satellitosis in human malignant astrocytomas.

Malignant astrocytomas often display histopathological heterogeneity. In the present study, we have molecularly characterized different areas within 4 such tumors to determine whether the tissue heterogeneity can be explained by differences in DNA constitution. Two tumors contained low grade areas, and the other 2 had areas with satellitosis. The tumors were examined for loss of heterozygosity with markers from chromosomes 9p, 10, and 17p and for amplification of the epidermal growth factor receptor gene. In each case, the high grade portion of the tumor displayed at least one of these structural alterations. However, identical alterations were found in the associated low grade or satellitosis areas of each tumor. Our data suggest that: (a) genetic alterations associated with tumor progression already occur in histopathologically low grade areas of high grade astrocytoma; (b) satellitosis associated with a high grade astrocytoma has to be considered as part of that tumor; and (c) tissue heterogeneity within a high grade astrocytoma is not a consequence of differences in DNA constitution at the loci that were examined.

[Headache and impaired consciousness due to the spontaneous intracranial hypotension syndrome]. / Hoofdpijn en verminderd bewustzijn veroorzaakt door het spontane liquorhypotensiesyndroom.

A 51-year-old man presented with a 6-week history of progressive headache, confusion and ataxic gate. The symptoms were not preceded by trauma or lumbar puncture. A CT-scan of the brain revealed bilateral subdural fluid accumulation and hyperdensities in the subarachnoid space. In view of the signs of a subarachnoid haemorrhage, angiography was performed but showed no indications of an aneurysm. An MRI-scan of the head revealed abnormalities in line with intracranial hypotension. CT-myelography of the whole spine revealed a cerebrospinal fluid leak at the level of the fifth and sixth thoracic vertebrae. The patient recovered completely after placement of an epidural blood patch at this level. Spontaneous intracranial hypotension shows clinical similarities with the symptoms following a lumbar puncture. In most cases it can be treated by conservative measures. However, invasive measures are sometimes necessary to close the defect in the meninges.

Prediction of spinal epidural metastases.

CONTEXT: Early diagnosis and treatment of spinal epidural metastases (SEM) is of the utmost importance to prevent neurological deficit due to spinal cord compression. Magnetic resonance imaging (MRI) has become the final tool in that diagnostic process. However, access to MRI is still limited in The Netherlands, requiring cost-effective use. It is generally acknowledged that patients with systemic cancer who present with a radiculopathy or myelopathy should undergo an MRI. However, the diagnostic policy in patients with systemic cancer who present with recently developed back pain is still a matter of debate. OBJECTIVE: To identify the patients with back pain in whom MRI can safely be omitted because of a low risk of SEM. METHODS: In a prospective series of 170 consecutive patients with cancer with recently developed back pain, prediction of spinal metastatic disease (SMD) and especially SEM was studied by means of a multivariate risk analysis of the parameters of the standard neurological evaluation (medical history, neurological examination, and plain films of the whole spine). Magnetic resonance imaging was used as the criterion standard. We calculated the risk implications of omitting MRI in patients with an estimated risk below different cutoff points. RESULTS: Spinal metastatic disease was diagnosed in 80 patients (47%); of these, 31 had SEM. A metastatic abnormality on plain films was the strongest independent predictor for SMD. Other important predictors were night pain, progressive pain, and Karnofsky score. Advanced age, exacerbation of pain during recumbency, and osteoporotic fracture imply a low risk of SMD. Night pain and the Karnofsky score proved to be the main predictors for SEM. A plain film showing an osteoporotic fracture strongly decreased the risk of SEM. The discriminating value of the multivariate analysis was too low, and too few patients can be excluded from undergoing MRI on the basis of the standard neurological checkup. To identify all the patients with SMD (P<.01), MRI would be excluded in only 7 patients. Identification of all patients with SEM (P<.001) reduced the number of MRIs by 21 at the expense of plain films of the whole spine for any patient. CONCLUSIONS: Selection of patients with cancer with back pain at risk of SEM was not possible with the standard neurological checkup. After intake by the neurologist, the next step should be MRI of the whole spine.

A comparison of neuropsychological effects of thalamotomy and thalamic stimulation.

OBJECTIVE: The neuropsychological effects of thalamotomy and thalamic stimulation in patients with severe drug-resistant tremor due to PD, essential tremor (ET), or MS were compared in a randomized trial. METHODS: Complete neuropsychological evaluations at baseline and 6 months after surgery were obtained in 62 patients who underwent thalamotomy (n = 32: 21 PD, 6 ET, 5 MS) or thalamic stimulation (n = 30: 19 PD, 7 ET, 4 MS). RESULTS: Six months after thalamotomy, a decline was seen in the scores of the Stroop Color-Word Test, with the exception of the interference score. In the thalamic stimulation group, no significant changes were found on any of the cognitive tests. Age, diagnosis, disease severity, and baseline cognitive status were not correlated to cognitive changes. A difference in score changes between right- and left-sided surgery was found in verbal fluency and Stroop Test scores after both thalamotomy and thalamic stimulation. CONCLUSIONS: Both thalamotomy and thalamic stimulation are associated with a minimal overall risk of cognitive deterioration. Verbal fluency decreased after both left-sided thalamotomy and thalamic stimulation.

Morbidity and mortality following pallidotomy in Parkinson's disease: a systematic review.

OBJECTIVE: To study the frequency of morbidity and mortality associated with pallidotomy. METHOD: The authors searched the MEDLINE electronic database for pallidotomy articles reported between January 1992 and December 2000. They selected studies by the following criteria: original clinical data, unequivocal description of morbidity and mortality, and unselected consecutive cases. The authors extracted the following data: number of patients, unilateral or bilateral procedures, age, localization technique, follow-up time, number of patients with adverse effects, number of patients with permanent adverse effects (>3 months), types of adverse effects, and mortality. RESULTS: For unilateral pallidotomy, 12 prospective studies included 334 patients. Of these patients, 30.2% (95% CI, 25.3 to 35.2) had adverse effects, and 13.8% (95% CI, 10.1 to 17.5) had permanent adverse effects. A symptomatic infarction or hemorrhage occurred in 3.9% (95% CI, 2.1 to 6.6). The mortality rate was 1.2% (95% CI, 0.3 to 3.0). In the series with microelectrode recording, the frequency of adverse effects was 14.4% (95% CI, 4.7 to 24.1) higher and the frequency of stroke was 4.9% (95% CI, 1.4 to 8.4) higher. The most frequent adverse effects were problems with speech (11.1%) and facial paresis (8.4%). For bilateral pallidotomy, five historical cohort studies including 20 patients were available for review. Fourteen patients had an adverse effect, and the most frequent adverse effects were impairments of speech and cognition. CONCLUSIONS: The risk of permanent adverse effects associated with unilateral pallidotomy was 13.8%. A symptomatic infarction or hemorrhage occurred in 3.9% of patients, and the associated mortality rate was 1.2%.

Quality of life after brachytherapy in patients with glioblastoma multiforme.

As quality of life (QoL) is perhaps the most important outcome for patients treated for glioblastoma multiforme (GBM), we measured QoL in GBM patients after brachytherapy. QoL was assessed by questionnaires for both patients and partners before brachytherapy and at various times during follow-up in 21 GBM patients by an extension of the Rotterdam Symptom Checklist (e-RSCL), consisting of four subscales. The Karnofsky Performance Scale (KPS) was also measured. Analysis of variance was done to evaluate the direct effect of brachytherapy (visit 1-2, short-term) and during follow up (visit 1-4, longer-term). Significant short-term effects were found for two subscales of the e-RSCL. Longer-term effects were found for all four subscales and for the KPS. A high correlation between partner and patient's QoL assessment was found. QoL in GBM patients after brachytherapy can therefore be carefully monitored with a subjective instrument such as the e-RSCL. Patients and partners experience QoL equally.

Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas.

The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the radiation effect of glioblastomas. The advantage of OMS is maintenance of the characteristics of the original tumour, which is lost in conventional cell cultures. OMS prepared from four glioblastomas were treated with hypofractionated radiation with a radiobiologically equivalent dose to standard radiation treatment for glioblastoma patients. After treatment, the histology as well as the cell proliferation of the OMS was examined. After radiation, a significant decrease in cell proliferation was found, although no histological damage to the OMS was observed. The modest effects of radiation on the OMS are in agreement with the limited therapeutic value of radiotherapy for glioblastoma patients. Therefore, OMS seems to be a good alternative for cell lines to study the radiobiological effect on glioblastomas.

Differential expression of CD44 splice variants in the normal human central nervous system.

Cluster of differentiation 44 (CD44) is a broadly distributed group of glycoproteins that are involved in many functions related to cell-cell and cell-matrix interactions. In the present study, the expression of the standard form of CD44 (CD44s) and of CD44 variants (CD44v) was explored immunohistochemically on frozen sections of various areas of the human CNS. The results demonstrate that CD44s epitopes are expressed predominantly by white matter astrocytes, whereas different CD44 variant molecules are present in neurons, on axonal membranes, on endothelium or on choroid plexus epithelium. Interestingly, neurons and axons differentially expressed CD44 variant epitopes but consistently lack immunoreactivity for CD44s epitopes. Another interesting finding was that some CD44 variant epitopes expressed by neurons were localized in the cytoplasm instead of on the cell membrane. The broad distribution of variant CD44 molecules in the human CNS suggests that CD44 may play an important role in many biological processes in the CNS.

Human malignant astrocytes express macrophage phenotype.

Six well-characterized specimens of cultured astrocytoma cells were investigated with a panel of macrophage markers. Our results show that the macrophage markers OKM-1(CD11b), OKM5(CD36), EBM11(CD68), HAM56, Factor 13, alpha-1-antichymotrypsin, alpha-1-antitrypsin, ferritin and lysozyme are clearly reactive to neoplastic astrocytes whereas astrocytes in normal brain specimens are not reactive. In order to obtain further confirmation concerning the reactivity of tumor cells in vivo, we simultaneously measured by flow cytometric analysis DNA content and HAM56 immunoreactivity in a freshly obtained tumor specimen. In this experiment we found a marked reactivity of aneuploid cells to HAM56. The macrophage phenotype of malignant astrocytes may reflect a similarity in functions of these cells and tumor-associated macrophages which promote tumor growth via the production of growth factors and angiogenic factors. Furthermore, our findings implicate that demonstration of macrophages within malignant astrocytomas by using macrophage-specific antibodies must be cautiously considered.

Accelerated radiotherapy in glioblastoma multiforme: a dose searching prospective study.

The EORTC Radiotherapy Cooperative Group performed a prospective phase II study in glioblastoma multiforme using accelerated radiotherapy in escalating doses. The aims of the study were to investigate acute and late toxicity as well as tumor response and survival. Only the CT-enhanced tumor zone plus a margin of 2-3 cm were treated (mean volume, 1034 +/- 477 cm3). Radiotherapy was administered with 5-18 MV photons. The radiation schedule consisted of 3 fractions of 2 Gy/day, separated with at least 4 h. The first group of patients was scheduled to receive a total dose of 42 Gy, 21 fractions in 9 days. The total dose was then escalated up to 48 Gy (24 fractions in 10 days), 54 Gy (27 fractions in 11 days) and 60 Gy (30 fractions in 12 days). The numbers of patients entered in each dose-level group were 15, 17, 18 and 16, respectively. Acute toxicity was mild, nausea/vomiting was absent in 91% of the patients. In 80% of the patients the neurological condition improved or remained stable compared with the start of radiotherapy but in 58% of the patients steroids were necessary, either increased in dose or initiated. Acute toxicity did not increase with increasing radiation doses although patients treated with 60 Gy more often required steroids than the other groups. Late toxicity was strongly suspected in 2 patients receiving 52 Gy and 56 Gy, respectively. Within the whole group of 66 patients only one recurrence outside the primary site was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of perfusion enhancement after administration of nicotinamide and carbogen in patients with glioblastoma: a 99mTc-HMPAO SPECT study.

BACKGROUND: Nicotinamide (NAM) and carbogen both have been shown to enhance the radiation effect in rodent tumour models and are currently being tested in clinical trials. These agents have demonstrated to act against hypoxia and one of their underlying mechanisms could be an increase of tumour blood perfusion. PURPOSE: To analyse the effect of both agents on normal brain perfusion and tumour perfusion in patients with glioblastoma. MATERIALS AND METHODS: Nineteen patients with glioblastoma were studied with 99mtechnetium-hexamethylpropyleneamine oxime single photon emission computed tomography (99mTc-HMPAO SPECT) before and after administration of carbogen and/or NAM. Another six patients were studied with the same procedure but without any flow modulator and were used as controls. RESULTS: Although the variations between patients were large, no significant enhancement in mean tumour and normal brain perfusion could be demonstrated with NAM or carbogen compared to the control patients. Also no consistent changes in the mean perfusion ratio between tumour and surrounding normal brain were found, suggesting an absence of a selective perfusion effect. CONCLUSIONS: No significant influence of carbogen and/or NAM on tumour perfusion and normal brain perfusion could be detected with SPECT in patients with glioblastoma.

Ambulatory monitoring of tremor and other movements before and after thalamotomy: a new quantitative technique.

Tremor, e.g. in Parkinson patients, often shows large spontaneous fluctuations in severity over the day, to such an extent that a short observation is usually not sufficient to assess the overall severity or the effect of a treatment. Since momentary impressions of the tremor can thus be misleading, long-term ambulatory recordings would be helpful in the evaluation of severity and treatment effectiveness. As existing methods for long-term tremor registration have several shortcomings, a new method is proposed: an algorithm was designed to discriminate tremor from other movements and to describe the amount (i.e. the proportion of tremor or movements per time unit) as well as the intensity (i.e. average acceleration amplitude) of the two types of movement. In the evaluation of the severity of tremor both the amount and intensity of tremor episodes are of importance. The algorithm was tested on 24-h analog tape recordings of wrist-movement in 10 young and 10 aged controls, as well as in 8 patients with tremor--both before and after a tremor relieving thalamotomy. The algorithm scored movements as 'tremor' exclusively in patients prior to the operation. Fluctuations in tremor severity over the day were detected, and tremor could be discriminated from non-pathological movements. Moreover, following thalamotomy, motor slowing (bradykinesia) was detectable using this algorithm. Based on these test results, a miniaturized device in wrist-watch format is now being developed for long-term registrations.

Stereotactic rostral mesencephalotomy in cancer pain and deafferentation pain. A series of 40 cases with follow-up results.

Stereotactic rostral mesencephalotomy was performed in two groups of patients to investigate the long-term results in regard to pain relief. A standardized technique of target localization with ventriculography was used. Group A consisted of 33 patients with otherwise intractable pain due to cancer. Group B consisted of seven patients with deafferentation pain. Long-term pain relief was good (57%) for Group A and nonexistent for Group B patients. It is concluded that stereotactic rostral mesencepthalotomy is a valuable means for treating nociceptive cancer pain in lateral syndromes, but is of no value in neuropathic pain. Anatomical correlates for the results obtained are discussed and a hypothesis on the plasticity of the neo- and paleospinal afferent systems is formulated.

Successful stereotaxic evacuation of an acute pontomedullary hematoma. Case report.

A healthy young woman developed a rapidly progressive pontomedullary lesion 24 hours after delivery of her first child. The lesion was shown on computerized tomography (CT) to be a primary hematoma. Stereotaxic aspiration was carried out, and the patient recovered. Angiography and CT scanning demonstrated a vascular lesion compatible with an arteriovenous malformation.

A prospective comparison between three-dimensional magnetic resonance imaging and ventriculography for target-coordinate determination in frame-based functional stereotactic neurosurgery.

OBJECT: The purpose of this prospective study was to compare stereotactic coordinates obtained with ventriculography with coordinates derived from stereotactic computer-reconstructed three-dimensional magnetic resonance (3D-MR) imaging in functional stereotactic procedures. METHODS: In 15 consecutive patients undergoing functional stereotactic procedures, both preoperative frame-based stereotactic 3D-MR imaging and intraoperative ventriculography were performed. Differences between 3D-MR imaging and ventriculography in X, Y, and Z coordinates of the anterior commissure (AC), posterior commissure (PC), and target area were calculated, as well as the 3D distance between the position of AC, PC, and target within stereotactic space as obtained using both methods. The position of the stereotactic MR imaging fiducial markers measured using 3D-MR imaging compared well with the markers' known position embedded in the software (mean error 0.4 mm, maximal error for an individual slice 1.2 mm). For the individual coordinates, only for Y-PC was a difference found between 3D-MR imaging and ventriculography that significantly exceeded half the size of a pixel, the theoretical limit of precision when using a digitized imaging technique. However, the mean difference was smaller than 1 mm. The mean 3D distance between the 3D-MR imaging- and ventriculography-derived coordinates was 1.09 mm for AC, 1.13 mm for PC, and 1.29 mm for the targets. CONCLUSIONS: With these data it is shown that there is sufficient agreement between ventriculography-derived and 3D-MR imaging-derived stereotactic coordinates to justify the use of 3D-MR imaging target determination in frame-based functional stereotactic neurosurgery.

Giant intracranial mucocele.

A 21-year-old man was admitted to hospital because of recent anosmia and liquorrhoea. He also complained of moderate headache and concentration problems in the past few years. On CT scan and MRI scans a big subfrontal process was seen, partially solid and partially cystic. Neurosurgical and histological findings proved that the lesion was an osteoma of the anterior skull base, concomitant with an intradurally extending mucocele.

Treatment of colloid cysts of the third ventricle by stereotactic aspiration.

Four patients are described with a colloid cyst in the anterior part of the third ventricle, causing obstruction of the foramina of Monro. Stereotactic aspiration of the cyst was performed after exact neuroradiological localization, including CT scan. The great advantages of the technique presented are discussed.

Posteroventral pallidotomy in movement disorders.

Since 1992 there has been renewed interest in pallidotomy now that the limitations and adverse effects of long-term dopaminergic therapy have become more apparent and more difficult to control in patients with advanced Parkinson's disease. The authors describe the effect of pallidotomy in 19 patients, sixteen of whom had advanced Parkinson's disease with painful dystonia and/or response fluctuations with severe akinesia while in "off" and dyskinesias while in "on". One patient had cortico-basal degeneration with rigidity, one patient had secondary dystonia and one had dystonic posturing due to Wilson's disease. Fifteen patients underwent unilateral pallidotomy, four patients had a staged bilateral procedure. Follow-up ranged from 3 to 42 months (mean 18 months). All patients with peak-dose dyskinesias and/or dystonia had marked reduction of symptoms, including the cases of Wilson's disease and secondary dystonia. The akinesia and rigidity scores of Parkinson-patients in "off" were greatly reduced, mainly but not only on the contralateral side. Evaluation by the patients showed remarkable improvement of symptoms in 79%, leading to substantially improved functional abilities in 68%. In this series the decrease in dopamine-response fluctuations, dystonia, hypokinesia and rigidity with functional improvement as judged by examiners and patients reflect a significant regain of independence.