Hansdetlef Wassmann

Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

Using single-photon emission tomography (SPET), the radiopharmaceuticall,-3-iodine-123-α-methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours.

Non-invasive grading of primary brain tumours: Results of a comparative study between SPET with123I-α-methyl tyrosine and PET with18F-deoxyglucose

Use of iodine-123-α-methyl tyrosine (123I-IMT) allows investigation of the amino acid transport rate in gliomas. It was the aim of this study to compare the value of measurement of glucose metabolism with that of measurement of123I-IMT uptake for the non-invasive grading of brain tumours. The study population comprised 23 patients with histopathologically proven primary brain tumours; 14 had high-grade gliomas, and nine low-grade brain neoplasms. Glucose metabolism was studied using an ECAT EXACT 47 positron emission tomography (PET) camera and fluorine-18 fluorodeoxyglucose (18F-FDG);123I-IMT uptake was measured with the triple-headed single-photon emission tomography (SPET) camera, MULTISPECT 3.18F-FDG and123I-IMT uptake was quantified as ratios between the uptake by the tumour and contralateral regions of reference. Glucose metabolism and amino acid uptake of the brain tumours correlated significantly (r=0.71,P <0.001). Assuming discrimination thresholds between high-grade and low-grade tumours of 0.8 for18F-FDG uptake and 1.8 for123I-IMT uptake, the accuracy values of18F-FDG PET and123I-IMT SPET for differentiating between high-grade and low-grade tumours were 21/23 (91%) and 19/23 (83%), respectively. The difference in diagnostic performance was not significant on receiver operating characteristic analysis (P >0.4). It is concluded that there is no major difference between the PET investigation of glucose metabolism and the less expensive SPET measurement of amino acid uptake in terms of their accuracy in evaluating the malignancy grade of primary brain tumours. This encourages the performance of further studies to analyse the potential impact of123I-IMT SPET on the therapeutic management of patients with brain tumours.

Intracranial metastasis of a spinal myxopapillary ependymoma. A case report

A 37-year-old man exhibited a suprasellar tumor which histologically proved to be a myxopapillary ependymoma. Since these gliomas are virtually restricted to the cauda equina region, magnetic resonance imaging (MRI) was performed which revealed multiple spinal tumors. The present case seems to be the first report on spontaneous intracranial seeding of a spinal myxopapillary ependymoma.

Problems of the Glasgow Coma Scale with early intubated patients

The Glasgow Coma Scale is probably the most common grading scale in neurotraumatology all over the world. Its validity concerning severity and prognosis of the injury has been established in the Anglo-American literature. Data derived from the German rescue system, however is different from the Anglo-American in some respects. The analysis of a well-defined group of German trauma patients with moderate and severe head injuries (n=299) shows that low Glasgow Coma Scores (GCS 3–6) established during the first two posttraumatic days must not correspond directly to the outcome after one year. Especially for the best Glasgow Coma Score during the day after the injury, GCS 4 had a poorer collective long-term prognosis than GCS 3. Therefore, German data from head injury studies based on the Glasgow Coma Scoring are difficult to compare to those cited in the Anglo-American literature. Any statistical analysis of a so called “ranking scale” which does not satisfy its own claims under special conditions is difficult.

Sequential scintigraphic strategy for the differentiation of brain tumours

Abstract.Both thallium-201 and iodine-123 α-methyltyrosine (123I-IMT) have been shown to be useful in the diagnostic evaluation of brain tumours. The aim of this study was to investigate the respective contributions of 201Tl and 123I-IMT single-photon emission tomography (SPET) in the non-invasive evaluation of intracerebral tumours. We analysed 65 patients with the following brain tumours: 8 non-neoplastic lesions, 4 meningiomas, 12 low-grade gliomas, 28 high-grade gliomas, 11 metastases and 2 high-grade lymphomas. 201Tl SPET and 123I-IMT SPET were performed [start of 201Tl SPET: 15 min p.i. (early) and 180 min p.i. (delayed); start of 123I-IMT SPET: 15 min p.i.]. The intensity of uptake was quantified as the ratio between tracer accumulation in the tumour and in the contralateral hemisphere. None of the non-neoplastic lesions or low-grade gliomas expressed marked 201Tl uptake. All malignant tumours except one small metastasis and all meningiomas except one small, cystic and degenerated lesion showed significant 201Tl accumulation [Tl(15’)>2.0]; 123I-IMT uptake was either absent or intermediate in non-malignant lesions except in two low-grade gliomas; the highest levels were observed in high-grade gliomas followed by metastases and lymphomas (mean IMT: 2.7 vs 2.1 vs 1.8), with metastases showing a high variability in 123I-IMT uptake (range: 0.8–3.6). Using 201Tl to distinguish non-neoplastic lesions from malignant tumours and meningiomas, 63 of 65 patients were characterised correctly. In the latter group, high-grade gliomas were correctly identified in 27 of 28 cases by their amino acid uptake. It is concluded that the combination of 201Tl and 123I-IMT surpasses the accuracy of each single test in the differentiation of space-occupying lesions of the brain. Based on these preliminary results, a sequential strategy is proposed involving an initial 201Tl SPET study and an additional 123I-IMT SPET study in the event of positive 201Tl uptake.

Revascularization procedures in internal carotid artery pseudo-occlusion

SummaryBackground. Surgical treatment of patients with suspected internal carotid artery (ICA) pseudo-occlusion and reduced cerebrovascular reactivity (CVR) is still uncertain regarding the diagnostic procedures, the risks and the optimal timing as well as performance of revascularization. Method. From 1983–2001, 781 patients with symptomatic ICA stenosis were treated surgically. In 53 patients, a final diagnosis of extracranial ICA pseudo-occlusion was established by repeating Digital Subtraction Angiography (DSA). Angiographical findings were anterograde “string-like” filling of ICA beyond the carotid bifurcation or retrograde filling of the proximal, so called “occluded” extracranial ICA, extending up to the skull base. The CVR was reduced. All patients underwent direct surgery of extracranial carotid artery. Diagnostic parameters, peri-operative risks and postoperative course of these patients were evaluated. Findings. In 40 patients (75.5%) a successful revascularization of ICA was possible. ICA pseudo-occlusion was in all cases of atheromatous origin, moreover in 8 patients combined with a floating thrombus, distal to the stenosis. Thrombectomy was done by means of Fogarty catheter. In 13 patients (24.5%), a surgical re-opening of the ICA lumen was not possible. Five of these patients showed in DSA an anterograde “string sign”, eight presented retrograde filling of ICA reaching the skull base. Peri-operative mortality was 1.9%, peri-operative morbidity was 7.5%. After a 4 years (mean) follow-up, 95% of the reopened ICA remained patent. Conclusion. In patients with explicit carotid artery occlusion signs, careful selective DSA should be compulsory with a late series to detect ICA pseudo-occlusion. There is a chance for extracranial reopening ICA, even with compromised CVR, if anterograde “string like” or retrograde filling of proximal so called “occluded” ICA as far as the skull base is angiographically identified.

Dimethyl sulfoxide increases latency of anoxic terminal negativity in hippocampal slices of guinea pig in vitro.

Dimethyl sulfoxide (DMSO), which is widely used as a solvent for a variety of drugs, was used in the present study to investigate its ability to increase the hypoxic tolerance of brain tissue in vitro. DC-potentials and evoked potentials (EP, Schaffer collateral stimulation) were recorded in the CA1 region of hippocampal slices from adult guinea pigs. The latencies of the negative DC-potential shift (anoxic terminal negativity, ATN) after onset of hypoxia (95% N2, 5% CO2) were determined during superfusion with artificial cerebrospinal fluid (aCSF) or DMSO 0.4% dissolved in aCSF, respectively. The latencies of ATN were increased by DMSO application from 7.5+/-0.9 min (mean +/- SEM) under control conditions (n = 38) to 11.1+/-1.3 min with DMSO (n = 22, P < 0.01). These results demonstrate a neuroprotective effect of DMSO.

Combined Radiochemotherapy with Paclitaxel in the Treatment of Malignant Glioma

Background: Paclitaxel is a radiosensitizing agent that shows a synergistic effect with radiation in malignant glioma cells. A phase I/II trial was performed in order to evaluate both feasibility and outcome of combined radiochemotherapy in malignant glioma. Patients and Methods: 56 patients were included in the trial. Paclitaxel was administered on days 1–4, 15–18 and 29–32 18 to 24 hours prior to irradiation. Radiotherapy with 60 Gy in conventional fractionation was initiated on day 2. 31 patients were included in a dose-escalation trial starting with 20 mg/m2/d and increasing up to 60 mg/m2/d in 10-mg steps. Additional 25 patients were treated with 50 mg/m2/d. Results: The regimen was very well tolerated with minimal subjective impairment such as sickness or weakness. Maximal tolerable dose was 50 mg/m2/d, with neutropenia being the dose-limiting toxicity. There were four allergic reactions and five thromboembolisms; furthermore, one patient with a normal blood count died due to pneumonia. The median survival was 12 months, and significantly favorable factors were a young age, a lower tumor grade (grade 3) and a complete resection. Varying the paclitaxel dose had no influence on outcome. Conclusions: Combined radiochemotherapy with paclitaxel in the treatment of malignant glioma was well tolerated. Maximal tolerable dose was 50 mg/m2/d. There was no increase in survival compared with results reported in the literature.Hintergrund: Paclitaxel ist eine strahlensensibilisierende Substanz, die auch bei Gliomzellen eine synergistische Wirkung zeigt. Wir führten eine Phase-I/II-Studie durch, um die Toxizität und erste Ergebnisse der kombinierten postoperativen Radiochemotherapie bei malignen Gliomen zu evaluieren. Patienten und Methode: 56 Patienten wurden in die Studie eingeschlossen. Paclitaxel wurde an den Tagen 1–4, 15–18 und 29–32 18 bis 24 Stunden vor der Bestrahlung gegeben. Diese erfolgte mit 60 Gy in konventioneller Fraktionierung ab Ta 2. 31 Patienten nahmen an der Dosiseskalationsstudie teil, die mit Paclitaxel 20mg/m2/d bis 60 mg/m2/d in 10-mg-Schritten durchgeführt wurde. Weitere 25 Patienten wurden mit 50 mg/m2/d behandelt. Ergebnisse: Das Regime wurde sehr gut vertragen. Es trat keine Übelkeit oder Reduktion des Allgemeinzustandes auf. Die maximal tolerable Dosis war 50 mg/m2/d. Dosislimitierend war eine Grad-4-Neutropenie bei 60 mg/m2/d (Tabelle 1). Vier allergische Reaktionen und fünf thromboembolische Ereignisse waren zu verzeichnen. Ein Patient starb an einer Pneumonie bei normalem Blutbild. Das mediane Überleben betrug 12 Monate. Signifikant günstige prognostische Faktoren waren junges Patientenalter, Grad-3-Tumoren (Abbildung 1) und komplette Resektion (Abbildung 2). Die Paclitaxeldosis hatte keinen Einfluss auf das Therapieergebnis. Schlussfolgerung: Die kombinierte Radiochemotherapie mit Paclitaxel war gut verträglich. Die maximal tolerable Dosis betrug 50 mg/m2/d. Im Vergleich zu Literaturdaten konnte keine Verbesserung des Überlebens festgestellt werden.

High amino acid uptake in a low-grade desmoplastic infantile ganglioglioma in a 14-year-old patient

Amino acid uptake is higher in high-grade than in low-grade gliomas; this is the rationale for using radioactively labelled amino acids for the non-invasive grading of brain neoplasms. We present a 14-year-old boy with a low-grade desmoplastic infantile ganglioglioma (DIG) that exhibited marked contrast enhancement on magnetic resonance imaging (MRI), but no signs of infiltration and only minimal surrounding edema. In this benign neoplasm the relative uptake of the radioactively labelled amino acid I-123-α-methyl tyrosine (IMT), determined using single-photon emission computed tomography (SPECT), was 3.24; it was considerably higher than that of eleven other pretherapeutic low-grade gliomas where it ranged from 1.06 to 1.94 and also markedly above the average value of 2.37 found in 20 high-grade gliomas. This case report illustrates that results from emission tomography with radioactively labelled amino acids must be interpreted with caution, particularly when rare tumor entities are considered in view of uncommon clinical or radiological findings.

Cerebral AL λ-amyloidoma: Clinical and pathomorphological characteristics. Review of the literature and of a patient

Background. Amyloid deposits within the brain can be found in a heterogeneous group of diseases. Some of them involve only the central nervous system (AD); others are of systemic origin. Isolated deposits either in the brain, cranial nerves or within the spinal neural structures are extremely rare. So far, we do not know the natural origin, nor the clinical course. Methods. We reviewed the overall published cases as far as available and added our own case to learn more about the natural history, clinical and imaging characteristics of this rare brain lesion. Results. Together with our own case, 27 patients with cerebral amyloidoma were collected in the literature. The lesion always occurred supratentorially, moreover in another two cases also infratentorially. The initial symptoms as well as the results of different neuroimaging features were not specific. There was no predominance for sex and localization. Diagnosis could only be established by histopathological examination after surgical intervention. No recurrence was seen after radical resection; but there was progression in some cases of tumor biopsy. Conclusion. Complete surgical removal of cerebral AL amyloidoma seems to be the only way to prevent progression or recurrence of such a brain lesion.