Volkher Engelbrecht

Neurological impairment and recovery in Wilson's disease: evidence from PET and MRI

We studied the relationship of regional cerebral glucose consumption (rCMRGlc) and striatal dopamine D2 receptor binding as assessed with positron emission tomography (PET) with the structural abnormalities of the brain in magnetic resonance images (MR), and the degree of neurological impairment in 18 patients with Wilsons disease (WD). The rCMRGlc was determined in the basal ganglia, the thalamus, the cerebral cortex, and the cerebellar hemispheres. The severity of neurological signs, defined by semiquantitative motor impairment scores, correlated highly (r = -0.80) with the reduction of striatal rCMRGlc. Clinical scores, striatal rCMRGlc, and the degree of MRI abnormalities showed no correlation with different indices of dopamine D2 receptor binding. Sequential PET measurements in three patients during treatment with chelating agents revealed a moderate increase of striatal rCMRGlc (in two patients) and a moderate to marked increase of striatal D2 receptor binding (in three patients) in association with clinical improvement. Our data suggest that the rCMRGlc represents a sensitive and objective measure for assessing and monitoring striatal and extrastriatal involvement in WD. The lack of correlation between the dopamine D2 receptor binding and striatal rCMRGlc and structural abnormalities may be explained by the wide spectrum of clinical manifestations and different responses to treatment in WD patients.

Imaging diagnosis of retroperitoneal ganglioneuroma in childhood.

Purpose. To demonstrate the typical appearance of retroperitoneal ganglioneuromas on CT and MRI.¶Materials and methods. Retrospective analysis of diagnostic imaging (five CT scans, three MRI scans) in five children aged 3–15 years with the histological diagnosis of ganglioneuroma.¶Results. The scans showed large (maximum 11 cm diameter), round or oval tumours with sharply defined margins. Intraspinal tumour involvement occurred in two cases. Comparing CT with MRI, MRI was more accurate in defining the intraspinal involvement. The ganglioneuromas were hypodense on unenhanced CT and showed moderate enhancement with administration of contrast medium. In three patients, CT demonstrated tumour calcification with a disseminated speckled pattern. On T1-weighted MRI the tumours were homogeneous and hypointense, showing marked enhancement after gadolinium administration. On T2-weighted scans the tumours were hyperintense.¶Conclusion. At the time of diagnosis, retroperitoneal ganglioneuromas are generally large tumours that can be shown well by CT and MRI. The appearance on CT more readily suggests the diagnosis, but MRI is superior for documenting local or intraspinal tumour extension and lacks radiation load.

Primitive Neuroectodermal Tumors of the Cerebral Hemispheres in Two Siblings with TP53 Germline Mutation

We report on two siblings (brother and sister) who developed cerebral PNETs at the age of 5 years and 6 months, respectively. Both children were treated by operation followed by polychemotherapy. The brother also received cranio-spinal irradiation. Nevertheless, the children died about 12 months and 24 months post-operatively due to extensive cerebral tumor recurrences. Shortly after having lost both of her children, the mother developed an intra-abdominal tumor, which was resected and histologically diagnosed as ovarian carcinoma. Because of this unusual familial clustering of tumors and a positive history of brain tumors and other cancers in several maternal relatives, we analyzed DNA isolated from both PNETs and the ovarian carcinoma as well as constitutional (leukocyte) DNA from the whole family for mutation of the TP53 tumor suppressor gene. This analysis revealed that all tumors were homozygous for a missense mutation at codon 213 (CGA => TGG) resulting in an amino acid exchange from arginine to tryptophane. The same mutation was present in one TP53 allele in the constitutional DNA of the mother and the children, indicating that the mother had transmitted a TP53 germline mutation to both of her children. Analysis of loss of heterozygosity at microsatellite markers from 17p confirmed deletion of the paternal (wild-type) allele in both PNETs. Further investigation of the PNETs by comparative genomic hybridization revealed multiple chromosomal abnormalities. Interestingly, some genomic changes were common to both PNETs, while many others were not, a finding suggesting substantial genomic instability, probably as a consequence of p53 inactivation.

Fast spin-echo MR imaging of the pediatric brain

On a 1.5-T MR unit conventional spin-echo (CSE) and fast spin-echo (FSE) images were obtained in 70 consecutive children ranging from 4 days to 13 years in age. They suffered from developmental retardation, neurodegenerative, ischemic or inflammatory diseases. In our prospective study artifacts, lesion conspicuity and general impression were compared between double-echo (proton density- and T2-weighted) CSE and single-echo (T2-weighted) FSE images. Phase artifacts from flowing blood were seen rarely on the FSE images, while motion artifacts appeared more frequently. Assessment of myelination in 43 children with unfinished myelination revealed no difference between FSE and CSE. The lesion conspicuity in 20 children with focal abnormalities compared favorably between FSE and CSE. There was no diagnostically relevant difference between FSE and CSE, although in FSE spin density images were missing. FSE sequences can be used in MR imaging of the pediatric brain without disadvantage and with a time reduction of 67–75%.

The value of new MRI techniques in adrenoleukodystrophy

Purpose. To evaluate the significance of new techniques in MRI examinations of the brain in children with X-linked adrenoleukodystrophy (ALD). Materials and methods. Five patients aged between 2 and 15 years with childhood ALD were examined with MRI. Following conventional spin-echo (CSE) sequences, a fast spin-echo (FSE) sequence with T2 contrast was performed in four patients, an FSE turbo-inversion- recovery (TIR) sequence in two, magnetization transfer contrast (MTC) imaging in two, and localized proton spectroscopy (MRS) in four patients. Results. FSE compared favorably with CSE with a time saving of 70 %. On TIR images the contrast between normal and demyelinated white matter was greater than on CSE and FSE images. Calculated MTC values revealed a severe MTC loss within the demyelinated regions and a moderate reduction in the border zones. In this way, calculation of MTC might be useful to differentiate between edematous changes and areas of irreversible demyelination. MRS revealed a reduction in N -acetylaspartate and an elevation in choline (Cho). The degree of MRS changes paralleled the severity of demyelination. A Cho elevation may precede visible demyelination on T2-weighted images. Conclusion. T2-weighted FSE sequences can replace CSE without any disadvantages and with effective time saving. The indication for MTC imaging and MRS in children with ALD is not yet finally defined. These new techniques may reveal the earliest signs of cerebral involvement or of disease progression, a matter of great importance in selecting the optimal therapeutic approach.

Proton MR spectroscopy of the lumbar spine in patients with glycogen storage disease type Ib

Glycogen storage disease type Ib is an autosomal recessive inherited metabolic disorder resulting from deficiency of the microsomal glucose‐6‐phosphatase enzyme system. Six patients (three of which were treated with granulocyte colony stimulating factor) suffering from this disease were examined using image guided localized proton magnetic resonance (MR) spectroscopy. The relative signal intensities of water and lipid protons of the lumbar spine were determined. Comparison was made with iliac crest biopsies in the glycogen storage disease type Ib patients and localized proton MR spectroscopic values of the lumbar spine obtained by thirteen healthy volunteers. The data demonstrate for the first time that hypercellularity and myeloid hyperplasia in subjects with glycogen storage disease type Ib due to functionally impaired leucocytes results in a strongly increased water proton signal with a very low or absent lipid signal in localized proton MR spectroscopy. Upon granulocyte colony stimulating factor treatment, the water proton signal in the lumbar spine is not further augmented. J. Magn. Reson. Imaging 2001;14:757–762.

Dynamische kontrastverstärkte MRT zur Beurteilung der Knochenmarksmikrozirkulation bei malignen hämatologischen Erkrankungen vor und während einer Thalidomidtherapie

ZusammenfassungFragestellung. Unser Ziel war die Beurteilung der Mikrovaskularisation und des antiangiogenetischen Effektes einer Thalidomidtherapie mittels dynamischer kontrastverstärkter MRT (d-MRT) bei unterschiedlichen hämatologischen Erkrankungen. Methodik. Bei 20 Normalpersonen, 20 Patienten mit Myelodysplastischen Syndromen (MDS), 10 Patienten mit Osteomyelofibrose (OMF) und 10 Patienten mit Multiplem Myelom (MM) wurde eine schnelle Gradientenechosequenz (Turbo fast low angle shot 2D) mit pumpengesteuerter Gd-DTPA-Applikation vor und bei 18 davon durchschnittlich 4,3 Monate nach Therapiebeginn mit Thalidomid durchgeführt. Zwei Perfusionsparameter (Amplitude und Austauschratenkonstante) wurden berechnet und es erfolgten ein statistischer Vergleich der Werte zwischen Probanden und Patienten sowie eine Korrelation der klinischen Verlaufsparameter der Patienten mit den d-MRT-Ergebnissen. Ergebnisse. Bei den Patienten wurden im Vergleich zu den Normalpersonen durchschnittlich höhere Amplituden (Normalpersonen 14,4±5,2; MDS 24,8±8,1; OMF 35,9±4,3; MM 23,4±3,6) und Austauschratenkonstanten (Normalpersonen 0,124±0,042; MDS 0,136±0,036; OMF 0,144±0,068; MM 0,131±0,034) gemessen. Bei 14 von 18 im Verlauf untersuchten Patienten konnte eine signifikante (p<0,005) Reduktion der Perfusionsparameter in der d-MRT unter Thalidomidtherapie nachgewiesen werden. Klinisch zeigten sämtliche dieser Patienten eine Krankheitsremission. Schlussfolgerungen. Bei den untersuchten hämatologischen Erkrankungen liegen im Vergleich zu Normalpersonen signifikant höhere d-MRT-Perfusionsparameter der Lendenwirbelsäule vor. Unter antiangiogenetischer Therapie mit Thalidomid kommt es im Falle eines Therapieansprechens zum Abfall dieser Werte.AbstractPurpose. The aim of the study was to measure microcirculation parameters by dynamic contrast-enhanced MRI (d-MRI) and to evaluate the anti-angiogentic effects during treatment with thalidomide in different hematologic malignancies. Methods. In 20 healthy normal persons, 20 patients with myelodysplastic syndromes (MDS), 10 patients with multiple myeloma (MM) and 10 with myelofibrosis (MF) a fast gradient echo sequence (Turbo fast low angle shot 2D) with a pump controlled bolus infusion of gadolinium-DTPA was performed before and in 18 of these after beginning (average of 4,3 months) of a thalidomide therapy. Two pharmacokinetic parameters – the amplitude and exchange-rate-constant – were calculated and a statistical comparison of these values between healthy persons and patients as well as a correlation with the clinical course was executed. Results. Compared with the normal controls the patients showed a higher amplitude (normal persons 14.4±5.2, MDS 24.8±8.1, MF 35.9±4.3, MM 23.4±3.6) and exchange-rate-constant (normal persons 0.124±0.042, MDS 0.136±0.036, MF 0.144±0.068, MM 0.131±0.034). In the d-MRI-follow-up examinations a significant (p<0.005) reduction of the amplitude and exchange rate constant values was evident in 14 of 18 patients undergoing a thalidomide therapy. Clinically all of these patients showed a therapy responding with complete or partial diseases remission. Conclusions. In patients with hematologic malignancies significantly higher d-MRI-microcirculation parameters of the lumbar spine can be demonstrated than in normal persons. During anti-angiogenetic treatment with thalidomide a decrease of these values was observed in case of a responding to therapy.

Bildgebende Diagnostik supradiaphragmaler Manifestationen extranodaler Non-Hodgkin-Lymphome

ZusammenfassungMaligne Lymphome werden in Hodgkinund Non-Hodgkin-Lymphome (NHL) unterteilt. Der vorliegende Beitrag beschäftigt sich mit der bildgebenden Diagnostik extranodaler NHL in supradiaphragmalen Manifestationsorten. NHL können in fast allen Geweben des Körpers auftreten und sind in einer primär extranodalen Manifestation sehr seltene Tumorkrankheiten. Die sekundäre Beteiligung im Rahmen einer generalisierten lymphoproliferativen Erkrankung ist dagegen häufiger und tritt auch bei HIV-Patienten als AIDS-definierende Erkrankung auf. Da gerade extranodale Lymphome die Erscheinungsform anderer maligner Tumore imitieren, ist eine direkte radiologische Diagnose ohne histologische Sicherung nicht in allen Fällen möglich.Der Beitrag schildert die typischen Manifestationsformen von NHL der Lungen, des Kopf-Hals-Bereiches einschließlich der großen Drüsen sowie in seltenen Lokalisationen wie dem Herzen oder der Mamma.AbstractMalignant lymphomas are differentiated into Hodgkins and non-Hodgkins-lymphoma (NHL). The following article discusses the imaging of extranodal NHL in supradiaphragmatic localizations. Lymphoma can affect nearly all tissues, and represent a rare entity as primary extranodal NHL. A secondary involvement of non-nodal tissue as consequence of a generalized lymphoproliferative disease is more common,and may be seen as well in HIV-positive patients defining AIDS. As extranodal lymphoma mimick the radiologic appearance of other malignant tumors, direct diagnosis without histologic analysis is often impossible. The article describes typical manifestations of lymphoma of the lungs, the head and neck area including the large glands, and rare localizations as the heart or the breast.

CT Appearance of a Renal Aspergilloma in a Patient with the Acquired Immunodeficiency Syndrome

The appearance of a unilateral renal aspergilloma on computed tomography is described in a 32-year-old man with acquired immunodeficiency syndrome (AIDS). Aspergillus infections are uncommon in the AIDS population. Only 9 cases of renal aspergilloma have been described in AIDS. The treatment performed was percutaneous drainage followed by antifungal drug administration and unilateral nephrectomy. This case report emphasizes the fact that renal fungal infections need to be considered in differential diagnosis of kidney infections in AIDS patients.

Radiological assessment of extranodal lymphoma: spectrum of disease

ZusammenfassungUnter primärer extranodaler Lymphommanifestation im engen Sinne wird die primäre Organmanifestation eines malignen Lymphoms unter Ausschluß von Thymus, Milz, dem Waldeyerschen Rachenring, des Wurmfortsatzes und der Peyerschen Ileumplaques definiert. Im klinischen Alltag wird der Begriff jedoch auch für die sekundäre Organmanifestation einer lymphoproliferativen Grunderkrankung eingesetzt. Primär extranodale Lymphome sind überwiegend Non-Hodgkin-Lymphome; nur in ca. 1 % der Fälle manifestiert sich der Morbus Hodgkin primär extranodal. Bei den extranodalen NHL überwiegen die hochmalignen Formen. Wesentliche Ausnahme hiervon sind die vorwiegend niedrig malignen MALT-Lymphome. In der Vergangenheit wegen ihres langsamen und ortsständigen Tumorwachstums als Pseudolymphome betrachtet, sind sie erstmalig als eigene Entität in der „Revised-European-American-Lymphoma (REAL-)-Klassifikation“ von 1994 berücksichtigt worden. Die Häufigkeitsangaben schwanken für die primäre extranodale Manifestation zwischen < 10–25 %. Wesentlicher Grund hierfür ist die klassifikationsbedingte unterschiedliche Berücksichtigung extranodaler Regionen. Eine sekundäre Organbeteiligung durch ein NHL tritt in bis zu 40 % der Fälle im langfristigen Krankheitsverlauf primär nodaler Lymphome auf. Bei AIDS-Patienten, die an einem AIDS-assoziierten Lymphom erkranken, wird der sekundäre Organbefall in 85 % der Fälle häufig diagnostiziert. Der folgende Beitrag setzt sich mit der radiologischen Bildgebung extranodaler Lymphommanifestationen im thorakoabdominalbereich auseinander.SummaryPrimary extranodal lymphoma manifestation in the narrow sense is the term used to define the primary organ manifestation of a malignant lymphoma, excluding the thymus, spleen, Waldeyers tonsillar ring, the appendix and Peyers patches. However, in the clinical routine the term is also used for the secondary organ manifestation of underlying lymphoproliferative disease. Primary extranodal lymphomas are mainly non-Hodgkin lymphomas; there is primary extranodal manifestation of Hodgkins disease in only about 1 % of the cases. Among the extranodal NHL, the highly malignant forms predominate. A major exception is MALT lymphomas, which mainly show low slow growth. In the past, they were considered to be pseudolymphomas because of their slow and localized tumor growth. They were included as an entity of their own for the first time in the Revised European American Lymphoma (REAL) classification of 1994. The incidence data vary between < 10 % and 25 % for primary extranodal manifestation. The major reason for this is the difference in extranodal regions because of classification. Secondary organ involvment of an NHL occurs in up to 40 % of the cases in the long-term course of the disease in primary nodal lymphomas. Secondary organ involvment is frequently diagnosed in AIDS patients who develop an AIDS-related lymphoma (85 % of cases). The following contribution reports on the radiological imaging of extranodal lymphoma manifestation in the thoracoabdominal region.