Tomographic studies of rCBF with [99mTc]-HM-PAO SPECT in patients with brain tumors: comparison with C15O2 continuous inhalation technique and PET.

In 10 patients with malignant gliomas, the intracerebral distribution of [99mTc]-hexamethylpropylene-amine oxime [( 99mTc]-HM-PAO) was studied with single photon emission computed tomography (SPECT) in comparison with C15O2 steady-state inhalation technique to measure cerebral blood flow using positron emission tomography (PET). In all instances, the cerebral [99mTc]-HM-PAO distribution was comparable with the regional pattern of cerebral blood flow (rCBF) observed with PET. This was confirmed by a significant correlation of tumor to cortex and tumor to white matter ratios between these two experimental methods. However, the contrast between high and low activity regions in the SPECT scans was significantly less than that in the PET scans. Contrast enhancement of the SPECT scans was accomplished using a correction formula proposed by Lassen.

Brain and brain tumor uptake of L-3-[123I]iodo-alpha-methyl tyrosine: competition with natural L-amino acids.

SPECT studies with L-3-[123I]iodo-alpha-methyl tyrosine (IMT) were carried out in 10 patients with different types of brain tumors--first under fasting conditions (basal) and a week later during intravenous infusion of a mixture of naturally-occurring L-amino acids (AA load). An uptake index (UI) was calculated by dividing tissue count rates by the integral of plasma count rates. The UI decreased by 45.6% +/- 15.4% (n = 10, p less than 0.001) for normal brain and by 53.2% +/- 14.1% for gliomas (n = 5, p less than 0.01) during AA load compared to basal conditions, while two meningiomas and a metastasis showed only a minor decrease (23.9 +/- 5.7%, n.s.). Two pituitary adenomas could not be delineated on the SPECT scans. These data indicate that IMT competes with naturally-occurring L-amino acids for transport into normal brain and gliomas. Transport characteristics of IMT into tumors of nonglial origin appear to be different from those of gliomas. For both types of tumors, it is advisable to perform IMT-SPECT under fasting conditions.

SPECT studies of brain tumors with L-3-[123I] iodo-alpha-methyl tyrosine: comparison with PET, 124IMT and first clinical results.

L-3-[123I]iodo-alpha-methyltyrosine (123IMT) like tyrosine has been reported previously to have a high affinity for a transport system in the blood-brain-barrier (BBB). We examined the kinetic behavior of 124IMT in brain and plasma in two patients with glioblastoma using dynamic positron emission tomography (PET). 124IMT accumulated in brain and tumor tissue, reaching a maximum after 15 min, with a washout of 20% to 35% at 60 min postinjection. Animal experiments confirmed the accumulation of the intact tracer in murine brain, but there was no incorporation into proteins. SPECT studies with 123IMT in patients with different types of brain tumors showed increased uptake in 26 of 32 tumors. Although nonspecific uptake in tumors must be considered, the accumulation of IMT in normal brain and in some tumors with intact BBB suggests a specific uptake of IMT. As transport is the main determinant of initial amino acid uptake, 123IMT appears to be a suitable SPECT tracer of amino acid uptake although it is not incorporated into protein.

Immunohistochemical demonstration of proliferating cell nuclear antigen in glioblastomas: pronounced heterogeneity and lack of prognostic significance.

In order to evaluate a possible significance of the expression of proliferating cell nuclear antigen (PCNA) as clinically useful prognostic parameter, we retrospectively investigated a series of 40 glioblastomas by means of immunohistochemistry and compared the results to patient survival. All glioblastomas included in the study had been treated by operation, radiotherapy and intraarterial ACNU [3-(4-amino-2-methyl-5-pyrimidinylmethyl)-1-(2-chloroethyl)-1-nitr osourea] chemotherapy. Patient survival ranged from 2 months to 42 months (mean: 14.2 months). PCNA values varied widely, ranging from 0.5% to 75% (mean: 24.9%). Statistical analysis revealed no significant correlation between PCNA index and patient survival. Our study thus indicates that the expression of PCNA appears not to be a useful prognostic parameter for glioblastoma patients.

Effect of pharmacologic doses of zinc on the therapeutic index of brain tumor chemotherapy with carmustine.

To evaluate the potential differential effect of pretreatment with pharmacologic doses of the trace element zinc on the chemosensitivity of glioma cells and bone marrow cells for carmustine (BCNU), we performed in vitro and in vivo studies of zinc toxicity as well as of the combined treatment with zinc and the anticancer drug. We studied the in vitro effects on established human and rat glioma cell lines using a microcolorimetric growth assay and on murine bone marrow using a clonogenic assay for committed progenitor cells of the granulocyte-monocyte lineage. Zinc exposures of up to 100 microM for 120 h did not influence the growth of six of seven human glioma cell lines. Only U87MG demonstrated statistically significant toxicity during high zinc exposure (100 microM over 120 h). Dose-response growth curves generated for BCNU did not show protection against the anticancer agents by a 48-h pretreatment with different zinc concentrations. The clonogenic capacity of bone marrow cells was slightly reduced by in vitro culture for 24 and 48 h. Although this effect appeared to be more prominent in the presence of zinc supplementation, overall a statistically significant inhibition was seen only after exposure to a concentration of 100 microM zinc over 48 h. As compared with chemotherapy alone, in vitro pretreatment with 50 microM zinc over 48 h followed by chemotherapy resulted in an increased number of colony-forming unit-granulocyte monocyte (CFU-GM): CFU-GM increased by a factor of 2 for BCNU (60 microM x 2 h). This statistically significant in vitro chemoprotection would translate into a dose-protection factor of 1.5, i.e., for the same level of myelosuppression, zinc pretreatment would allow administration of a 50% increased dose of BCNU. The in vivo studies were performed in an s.c. xenograft model of the human glioma cell line U87MG in athymic mice. The maximal tolerable pretreatment with zinc was determined to be a 10-day course of daily i.p. injections of 10 mg/kg ZnCl2. The subsequent i.p. administration of the dose lethal to 10% of the mice (LD10) and of a 1.5 x LD10 dose of BCNU resulted in less bone marrow toxicity in pretreated animals than in non-zinc-pretreated mice as determined in a CFU-GM assay. Glioma colony-forming efficiency (CFE) assays, on the other hand, did not show any zinc-related difference in the BCNU sensitivity of U87MG.(ABSTRACT TRUNCATED AT 400 WORDS)

Outcomes in a consecutive series of 111 surgically treated plexal tumors: a review of the experience at the Louisiana State University Health Sciences Center.

OBJECT: The authors conducted a retrospective study of 107 consecutive patients with 111 brachial plexus tumors surgically treated at the Louisiana State University Health Sciences Center (LSUHSC). METHODS: During a 12-year period, from 1986 to 1998, 371 patients with lesions of the brachial plexus underwent surgery at LSUHSC. Among this group, 107 patients harbored 111 tumors of the brachial plexus. Neural sheath tumors were the most commonly found and included 33 neurofibromas (20 of which were associated with von Recklinghausen disease), 36 schwannomas, and 12 malignant neural sheath tumors. Of the non-neural sheath tumors, 13 were benign and 17 were malignant. Presenting symptoms included pain (59%), palpable mass (52%), paresthesias (30%), and paresis (29%). Anterior supraclavicular (82%) or posterior subscapular (18%) approaches were used to achieve gross-total (79%) or subtotal (21%) resection of tumor. The average follow-up period was 38.3 months or 3.2 years. Seventy percent of patients with benign neural sheath tumors became free from pain postoperatively or reported improvement in their preoperative pain status. Function remained intact or improved in 50% and remained stable postoperatively in another 20% of cases. Preservation of function was more likely in patients who presented intact and in those who had not undergone a previous attempted biopsy procedure or resection than in those in whom such manipulation had occurred. CONCLUSIONS: Resection of most plexal tumors is technically feasible and associated with acceptable morbidity and mortality rates.

Effects of recombinant human tumor necrosis factor on rodent gliomas and normal brain.

In a study examining the possible therapeutic effects of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) on malignant gliomas without expression of tumor necrosis factor (TNF)-receptors, RG-2 glioma cells were tested in vitro as well as in a rat experimental glioma model. A growth inhibition assay revealed no inhibiting effect in vitro up to a concentration of 20 micrograms/ml rHuTNF-alpha. Receptor-binding studies showed that RG-2 cells did not present specific receptors for rHuTNF-alpha. The pharmacokinetics of rHuTNF-alpha after intravenous injection were studied with respect to serum, tissue, and brain tumor concentrations and showed increased glioma concentrations of (mean +/- standard error of the mean) 0.47 +/- 0.18 ng TNF/mg brain compared to 0.15 +/- 0.05 ng TNF/mg brain in the normal contralateral hemisphere. No therapeutic effect on solid RG-2 gliomas could be observed after stereotactic injection of 7.3 micrograms rHuTNF/10 microliter buffer solution into the tumor in 10 animals. Immunohistochemical studies after stereotactic injection of rHuTNF-alpha showed total disappearance of the substance after 24 hours without internalization into tumor cells. Stereotactic injection of 7.3 micrograms rHuTNF 10 microliters into normal brain resulted in marked inflammatory response around the injection track, including microvascular thrombosis. These results demonstrate that rHuTNF has neither direct nor indirect cytotoxic activity on RG-2 glioma cells. Furthermore, before clinical use of rHuTNF-alpha in malignant gliomas, the authors suggest that receptor studies be done in each patient. In receptor-positive patients undergoing treatment with rHuTNF-alpha, precautions should be taken to prevent local encephalitic reactions.

Intracerebral hemorrhage due to cerebral amyloid angiopathy. Case report.

The case is presented of a 59-year-old man with cerebral amyloid angiopathy and three consecutive hemorrhages in the occipital lobes. The clinicopathological features and the relationship to Alzheimer's dementia are discussed. The correct treatment of intracerebral hemorrhage related to cerebral amyloid angiopathy is a matter of controversy.

Familial oligodendroglioma. Case report.

A case of familial oligodendroglioma, occurring in a mother and her daughter, is presented.

Congenital anaplastic astrocytoma with favorable prognosis. Case report.

A large intracranial tumor that caused macrocrania leading to dystocia was demonstrated by prenatal ultrasound examination. After birth, computerized tomography (CT) confirmed the presence of a giant supratentorial tumor with a large cyst. When the infant was 20 days old, the tumor was radically extirpated. Neuropathological examination revealed an astrocytoma with focal signs of anaplasia showing a macrocyst as well as multiple microcysts resulting from hemorrhages into the tumor. Although no adjuvant radio- or chemotherapy was administered, the child had nearly normal psychomotor development without clinical or CT evidence of tumor recurrence, and is now 3 years old.

Primary thalamic malignant fibrous histiocytoma of the dominant hemisphere causing severe neuropsychological symptoms.

A 45-year-old man with a malignant fibrous histiocytoma (MFH) of the left thalamus is reported. This tumor only rarely originates within the brain. Primarily intracerebral MFH usually has a superficial localization and rarely involves the deep cerebral structures. Our patient presented with complex neuropsychological symptoms, including aphasia, hemispatial neglect and acalculia. These findings are further supporting evidence for the role of the thalamus, particularly of its posterior parts, in language, speech and other neuropsychological functions.

[Space-occupying lesions in the pineal region--MRT using Gd-DTPA]. / Raumforderungen der Pinealisregion--MRT mit Gd-DTPA.

The results obtained from contrast-enhanced MRI in 21 patients with masses in the pineal region are reported. The use of gadolinium-DTPA results in intensive contrast uptake by the tumour; this produces better definition of the tumour and more exact delineation from neighbouring structures. This is of importance in judging resectability and in choosing the operative approach. During chemotherapy or radiotherapy, it provides reliable demonstration of the success of treatment and accurately demonstrates the size of the tumour and the presence of necrosis. On the other hand, histologic classification of pineal tumours is possible only occasionally.

[Contrast medium enhanced MRT of tumors of the posterior fossa in children and adolescents]. / Kontrastmittelunterstützte MRT von Tumoren der hinteren Schädelgrube im Kindes- und Jugendalter.

The results of contrast-enhanced MR in 24 children and adolescents with tumours of the posterior cranial fossa are presented. During initial diagnosis, the majority of tumours showed intensive enhancement with improved demarcation from neighbouring structures. The solid component of a cystic tumour, even when small and not visible on the original scan, could be demonstrated in all cases by means of gadolinium-DTPA. Post-operatively, T2-weighted scans regularly showed areas of high signal strength at the margin of the resection; in the absence of a mass or demonstrable progression, the significance of this is uncertain. In these cases gadolinium-DTPA, because of the function of the blood-brain barrier, greatly increases accuracy in demonstrating residual or recurrent tumours.

[MRT using gadolinium-DTPA in spinal intradural space-occupying lesions]. / MRT mit Gadolinium-DTPA bei spinalen intraduralen Raumforderungen.

The results of contrast enhanced MRI in 36 patients with suspected spinal intradural tumours are described. All intramedullary tumors showed distinctive enhancement and solid tumors could be delineated clearly, even if they were not clearly visible on unenhanced scans. The differentiation between neoplasm and non-neoplastic syrinx was markedly improved. The sensitivity of MRI for demonstrating intradural extramedullary tumours was greatly improved by gadolinium DTPA and even small lesions or flat meningeal infiltrates could be visualised. In addition, gadolinium DTPA improved the delineation and localisation of larger lesions, even if they had already been seen on unenhanced images.

Early effects of intra-arterial chemotherapy in patients with brain tumours studied with PET: preliminary results.

In ten patients with malignant gliomas the regional cerebral metabolic rate for glucose (rCMRGlc) was studied with positron emission tomography (PET) using 2-18F-deoxyglucose (18FDG) before and within 1 to 7 days after intra-arterial chemotherapy with the nitrosourea derivative ACNU (iaACNU). Three patients were studied before and after two iaACNU courses and one patients before and after three iaACNU courses. The early effects of iaACNU on tumour rCMRGlc were highly variable and appeared to be more pronounced after the first course of iaACNU than in later iaACNU courses, i.e. more pronounced in untreated patients. Although there was no clear correlation between the change of rCMRGlc following the first course of iaACNU and the clinical outcome in this small group of patients, the patient with the most pronounced decrease of tumour metabolism (-16.5%) after the first course of iaACNU exhibited full tumour remission for 12 months, while the patient with the most pronounced increase of tumour metabolism (+65%) after the first course of iaACNU developed rapid tumour progression. The first results indicate that early effects of intra-arterial chemotherapy may be observed with 18FDG PET, especially following the first course of iACNU. Further studies are needed to evaluate the predictive value of such studies for therapy response.

Investigations of brain tumours with 99Tcm-HMPAO SPECT.

The cerebral uptake of 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) as measured with the use of single photon emission computed tomography (SPECT) was studied in 66 patients with various types of brain tumours and quantified by tumour-to-cerebellum ratios. The uptake of 99Tcm-HMPAO by gliomas and meningiomas showed wide ranges of values. There were no significant differences among primary malignant gliomas (0.75 +/- 0.27, n = 25), recurrent malignant gliomas (0.81 +/- 0.25, n = 14) and benign gliomas (0.77 +/- 0.21, n = 9). Compared to gliomas, meningiomas exhibited a significantly higher 99Tcm-HMPAO uptake (1.14 +/- 0.31, n = 13, p less than 0.001) while the remaining four patients with tumours of various histopathology showed a low 99Tcm-HMPAO uptake. Three of the 66 patients were scanned immediately and again 2 h after injection and they revealed a decrease in tumour activity. No changes in the pattern of uptake were observed in two patients with gliomas which were studied before and after intra-arterial chemotherapy, but a decrease in tumour uptake was found in the glioma patient who was studied before and after radiotherapy. The results obtained with 99Tcm-HMPAO SPECT are in agreement with those on regional cerebral blood flow (rCBF) in brain tumours reported in the literature.

Completely reversible, severe, acute neurological deterioration with an otherwise asymptomatic, huge intradiploic calvarial epidermal cyst.

A huge, intradiploic, right temporoparietal epidermal cyst was known to be present, unchanged in extent, for over 14 years in a 55-year-old man. Although extreme mass effect was demonstrated by computed tomography scans, results of the neurological examination were within normal limits. Treatment of nausea and vomiting after vestibular testing caused somnolence and an acute diencephalic-mesencephalic syndrome of tentorial herniation. However, only moderate amounts of analgesics and sedatives were given. These symptoms disappeared as the pharmacological sedative effect diminished. Thereafter the tumor was resected radically. Neuropathological examination confirmed an epidermal cyst. Results of the postoperative neurological examination were within normal limits.

Cervicobrachialgia with congenital vertebral anomalies and diastematomyelia.

A case of diastematomyelia in an adult female patient is reported. The relationship of the cervicobrachialgia, which was the presenting sign, to the diastematomyelia and the congenital vertebral anomalies is discussed.