Stefan Palkovic

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.

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.

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.

Evaluation of the extension of cerebral gliomas by scintigraphy.

Background: Single photon emission computed tomography (SPECT) with 201T1 and 123I-α-methyl tyrosine (123I-IMT) are routine methods for the evaluation of brain tumors. 123-I-IMT transport across the blood brain barrier is mediated by an amino acid carrier, 201T1 accumulation is analogous to cerebral potassium uptake. Patients and Methods: To determine the differences in glioma extension as shown by the 2 methods, 17 patients with malignant gliomas were included in this comparative imaging study: astrocytoma III: n = 6, ependymoma III: n = 1, oligodendroglioma III: n = 1, glioblastoma IV: n = 9. The tomographic image sets were matched anatomically and the slices showing maximal tumor extension were identified in both image sets respectively. Tumor spread was compared visually and the tumor extension was quantified. Results: In gliomas WHO III tumor extension was delineated significantly larger by 123I-IMT-SPECT than by 201T1-SPECT (mean ± SD: 816 ± 281 pixels vs 600 ± 220 pixels, n = 8, p < 0.05). The size of glioblastomas was shown in a comparable manner by the 2 methods (977 ± 571 vs 1,051 ± 588, n = 9, ns, p = 0.57), but there were considerable regional differences between the area of 201T1 uptake and amino acid retention. In the whole group a weak but significant negative correlation between intensity of 201T1 uptake on the one hand and a ratio of the area as depicted by 123I-IMT vs area as depicted by 201T1 on the other hand, was found (n = 17, r = 0.49, p < 0.05). Thus the differences in the delineation of areas became smaller with increasing 201T1 uptake. Conclusions: These preliminary data indicate that the extension of gliomas is depicted differently by the 2 methods. 123I-IMT-SPECT shows a larger tumor extension especially in gliomas WHO III. Since 201T1 uptake has previously been shown to correlate with disruption of the blood brain barrier, 123I-IMT-SPECT may delineate tumor parts without endothelial leakage. This additional information may be helpful in planning surgical or radiation therapy. The advantages of 123I-IMT in this respect decrease with increasing 201T1 uptake and with increasing malignancy.Hintergrund: Die szintigraphische Darstellung der Verteilung des 201Thallium (201T1-SPECT) und der Aminosäure 123I-α-Methyltyrosin (123-I-IMT-SPECT) wird zur Evaluierung von Gliomen eingesetzt. Während die 201T1-Aufnahme analog zum zerebralen Kaliumeinstrom erfolgt, wird 123I-IMT mit Hilfe eines Aminosäurecarriers über die Blut-Hirn-Schranke transportiert. Ziel der Studie war ein Vergleich der Darstellng der Gliomausdehnung mit den beiden Verfahren. Patienten und Methode: 17 Patienten mit malignen Gliomen wurden mit beiden Verfahren untersucht (Astrozytom III: n = 6, Ependymom III: n = 1, Oligodendrogliom III: n = 1, Glioblastom IV: n = 9). Die Schnittbilder wurden anatomisch abgeglichen und die Schicht mit der jeweils maximalen Tumorausdehnung aufgesucht. Die Tumorfläche wurde gemessen und die Tumorausdehnung visuell beurteilt. Ergebnisse: Die Tumorausdehnung stellt sich bei den WHO-III-Tumoren mit 123-I-IMT-SPECT signifikant größer dar als in der 201T1-SPECT (Mittelwert ± Standardabweichung 816 ± 281 Pixels vs. 600 ± 220 Pixels, n = 8, p < 0,05, Abbildung 1a), die Größe der Glioblastome war in beiden Untersuchungen vergleichbar (977 ± 571 vs. 1051 ± 588, n = 9, p = 0,57, Abbildung 1b), wobei die visuelle Beurteilung in einigen Fällen regionale Unterschiede der Speicherintensität zeigte. In der Gesamtgruppe ergab sich eine schwache, aber signifikante negative Korrelation zwischen der maximalen 201-T1-Aufnahme einerseits und einem Quotienten aus der mit 123-I-IMT und der mit 201T1 dargestellten Fläche andererseits (n = 17, r = 0,49, p < 0,05, Abbildung 2). Somit wurde der Unterschied in der Flächendarstellung mit steigender 201T1-Aufnahme kleiner. Schlussfolgerungen:123I-IMT-SPECT zeigt bei Gliomen WHO-Grad III eine größere Tumorausdehnung als 201T1-SPECT. Da in früheren Untersuchungen gezeigt wurde, dass in den meisten Fällen eine Störung der Blut-Hirn-Schranke Voraussetzung für die zerebrale 201T1-Akkumulation ist, kann die 123I-IMT-SPECT möglicherweise Tumoranteile darstellen, die keine vermehrte endotheliale Durchlässigkeit aufweisen. Inwiefern diese Zusatzinformation zur Planung einer Operation oder einer Strahlentherapie eingesetzt werden kann, muss in zukünftigen Studien gezeigt werden. Mit steigender Malignität und zunehmender 201T1-Aufnahme nehmen die genannten Vorteile des 123I-IMT ab.

12 years' experience with intraoperative radiotherapy (IORT) of malignant gliomas

Background:Even after surgery and radiotherapy, malignant gliomas still have a poor prognosis. The authors report on their experience with IORT in 71 patients.Patients and Methods:From May 1992 to February 2004, 71 patients with malignant gliomas were treated with IORT. 26 patients suffered from grade III gliomas, 45 patients from glioblastomas (GBM). IORT was carried out using a standard electron tube and 9- to 18-MeV electrons. 52/71 patients who were primarily treated received 20 Gy IORT + 60 Gy postoperative radiotherapy, 19/71 patients with recurrences only received IORT (20–25 Gy).Results:The complication rates were 1.4% for wound infections and 5.6% for hemorrhage. Median disease-specific survival amounted to 14.9 months (gliomas III) and 14.2 months (GBM). The 2-year survival rates amounted to 26.9% (gliomas III) and 6.8% (GBM; p = 0.0296). Total versus subtotal resection had no significant influence on survival (p = 0.0741), nor had age, sex, tumor site, performance status, size, primary versus recurrence, and radiation dose. A comparison to a conventionally treated patient group did not show a significant survival improvement. 3 months after treatment, initial symptoms had improved in 59% (hemiparesis), 50% (aphasia), 50% (hemianopsia), and 60% (convulsions).Conclusion:IORT has been shown to be feasible; perioperative complication rates were not increased. Survival was generally not improved compared to a historical control group. Recurrences achieved the same survival as primary tumors, and GBM also had a slightly increased survival, thus being possible indications for IORT.Hintergrund:Auch nach Resektion und Strahlentherapie haben maligne Gliome nach wie vor eine schlechte Prognose. Die Autoren berichten über ihre Erfahrungen mit der IORT bei 71 Patienten.Patienten und Methodik:Von Mai 1992 bis Februar 2004 wurden 71 Patienten mit malignen Gliomen mit IORT behandelt. 26 Patienten hatten Grad-III-Gliome, 45 Patienten Glioblastome (GBM). Die IORT wurde mittels eines üblichen Elektronentubus und 9- bis 18-MeV-Elektronen durchgeführt. 52/71 Patienten wurden primär mit 20 Gy IORT + 60 Gy postoperativer Radiotherapie behandelt, 19/71 Patienten mit Rezidiven erhielten nur eine IORT (20–25 Gy).Ergebnisse:Die Komplikationsraten betrugen 1,4% für Wundinfektionen und 5,6% für Blutungen. Das mediane krankheitsspezifische Überleben lag bei 14,9 Monaten (Gliome III) und 14,2 Monaten (GBM). Die 2-Jahres-Überlebensraten betrugen 26,9% (Gliome III) und 6,8% (GBM; p = 0,0296). Der Resektionsstatus hatte keinen signifikanten Einfluss (p = 0,0741), ebenso wenig Alter, Geschlecht, Lokalisation, Allgemeinzustand, Größe, Primärtumor versus Rezidiv und Bestrahlungsdosis. Ein Vergleich mit einem konventionell behandelten Patientenkollektiv zeigte keine signifikante Verbesserung des Überlebens. 3 Monate nach Therapie hatten sich die initialen Symptome in 59% (Hemiparese), 50% (Aphasie), 50% (Hemianopsie) und 60% (Krampfanfälle) gebessert.Schlussfolgerung:Die IORT ist gut durchführbar; die perioperative Komplikationsrate war nicht erhöht. Das Überleben konnte im Vergleich zu einer historischen Kontrollgruppe insgesamt nicht verbessert werden. Rezidive erzielten dasselbe Überleben wie Primärtumoren, und auch GBM erreichten ein etwas besseres Überleben; diese beiden Gruppen sind am ehesten mögliche Indikationen für die IORT.

Coexistence of cerebral aneurysm and meningioma—Pure accident?

OBJECTIVES Coexisting intracerebral aneurysms and meningiomas occur relatively rarely, without a clear relationship, although an aneurysm can be located within a meningioma. The aim of this retrospective study was to identify possible explanations for the coexistence of these conditions and to present a rationale for treatment strategies. PATIENTS AND METHODS Ninety-five patients with coexistent meningioma and aneurysm were found in the National Library of Medicine, and 11 more patients were retrieved from our own database. RESULTS Co-occurrence of both pathologies, sometimes solitary, sometimes multiple, was mostly found in women (3:1). Clinical symptoms in the majority of patients were caused by tumour growth, whereas aneurysm rupture was seen only in a few cases. Consequently tumour resection was performed first in 58 out of the 95 patients, and aneurysm treatment in 38 patients. From available data, the mortality rate three decades before was approximately 40%, but decreased in the last years, due to microsurgical and endovascular techniques. All of our patients were alive after 1 year of follow-up. In patients with intratumoural aneurysms, only three published and one our own case, were treated for both pathologies. CONCLUSIONS The coexistence of meningioma and aneurysm seems to be a coincidence. Treatment should primary focus on the cause of presenting symptoms, but in cases with intratumoural aneurysm, the aneurysm should be treated first. Due to the development of microsurgical and endovascular techniques peri-procedural mortality and morbidity has decreased.

High uptake of L-3-[123I]iodo-α-methyl tyrosine in pilocytic astrocytomas

Despite a favourable prognosis, pilocytic astrocytomas may exhibit signs of malignancy on various neuroimaging modalities. This retrospective analysis was conducted to determine whether scintigraphic features of malignancy are also found on single-photon emission tomography (SPET) using L-3-[123I]iodo-α-methyl tyrosine (IMT) as a tracer. Twenty patients with pilocytic astrocytomas were retrospectively selected from a large series of patients referred for the evaluation of primary or recurrent brain tumours. IMT SPET was performed in 16 patients, positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was available in 10 of the patients and SPET using technetium-99m tetrofosmin or thallium-201 had been performed in 11. Image analysis was performed using standard protocols to determine how many patients exceeded the respective thresholds of malignancy. Features of malignancy were found in 7/16 IMT SPET studies, in 7/10 FDG PET studies and in 7/11 of the residual SPET investigations. A significant correlation of tumour size and IMT uptake in primary pilocytic astrocytomas indicated partial volume effects to partly account for the differential uptake behaviour (n=10, r=0.87, P<0.05). Differences in IMT uptake in primaries (1.7±0.6, n=10) and in recurrent tumours (2.3±0.7, n=6) did not attain statistical significance. IMT SPET results indicative of malignancy are regularly found in pilocytic astrocytomas, despite their good prognosis. No uptake may be detected in largely cystic or in small tumours.

Spontaneous spinal epidural haematoma: a therapeutical challenge? Report of an unusual case

We report the conservative treatment of a spontaneous spinal epidural haematoma attending with acute extensive neurological deficits, which resolved spontaneously. Spontaneous remission of spontaneous spinal epidural haematoma with severe neurological deficit is rare in the literature. An 80 year old man was admitted to our hospital presenting sciatica followed by rapid development of paraparesis and cauda equina syndrome, which represents a neurosurgical emergency. Magnetic resonance imaging revealed a multilevel epidural haematoma from L1 to L5. During the initial diagnostic procedure the symptoms started to decline unexpectedly, so the surgical intervention could be withdrawn. Twenty four hours after admission the patient was almost free of symptoms, mobile, and continent. Awareness and high index of suspicion, and a willingness to seek the prompt help of the imaging department, are crucial to successful management before the opportunity to treat is lost.