A family with pheochromocytoma-paraganglioma inherited tumour syndrome. Serial 18F-DOPA PET/CT investigations.

AIM: Hereditary pheochromocytoma-paraganglioma syndromes are characterized by multiple pheochromocytomas (PCC) and paragangliomas (PGLs), inherited in an autosomal dominant manner. Early detection and removal of tumours may prevent or minimize complications related to mass effects and malignant transformation. Having confirmed the diagnosis, it is important to localize the tumours and reveal their extent preoperatively. This study aimed to introduce 18F-DOPA PET/CT as a highly sensitive non-invasive diagnostic tool for early detection of mass lesions in patients with pheochromocytoma-paraganglioma inherited tumour syndrome and to report about its impact on patient management. PATIENTS, METHODS: We are currently supervising one of the largest documented families in Germany with genetically determined SDHD gene mutation. We performed 18F-DOPA PET/CT in order to detect tumours in asymptomatic gene carriers and enable subsequent surgical therapy. RESULTS: In seven patients undergoing 12 18F-DOPA PET/CT scans 17 lesions have been detected. Three of these lesions, located in the head and neck region, have had no morphologic correlate in CT and one had also no morphologic correlate in MRI. Of the six histologically analyzed lesions five have been tumors (PGL or PCC) and one has been a nodular hyperplasia. This means the 18F-DOPA PET/CT scan in our study group had a sensitivity of 83%. 18F-DOPA PET/CT investigations lead to change in the management in 5/7 studied patients (70%). CONCLUSION: The benefits of PET/CT in detection of pheochromocytoma and paraganglioma are well documented, but we are the first to use this technique for screening of a rare hereditary disease (estimated prevalence 0.3/100 000).

Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study.

Adding supraphysiologic doses of levothyroxine (L-T4) to standard treatment for bipolar depression shows promise, but the mechanisms underlying clinical improvement are unknown. In a previous pilot study, L-T4 treatment reduced depression scores and activity within the anterior limbic network. Here we extended this work in a randomized, double-blind, placebo-controlled study of patients with bipolar depression. Cerebral glucose metabolism was assessed with positron emission tomography and [F-18]fluorodeoxyglucose before and after 6 weeks of treatment with L-T4 (n=15) or placebo (n=10) in 12 volumes of interest (VOIs): the bilateral thalamus, amygdala, hippocampus, dorsal striatum and ventral striatum, and midline cerebellar vermis and subgenual cingulate cortex. Radioactivity in the VOIs, normalized to whole-brain radioactivity was taken as a surrogate index of glucose metabolism, and markers of thyroid function were assayed. Changes in brain activity and their association with clinical response were assessed using statistical parametric mapping. Adjunctive L-T4 treatment produced a significant decline in depression scores during the 6-week treatment. In patients treated with L-T4, we found a significant decrease in regional activity at P<0.05 after Bonferroni correction in the left thalamus, right amygdala, right hippocampus, left ventral striatum and the right dorsal striatum. Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate were correlated with a reduction in depression scores (P<0.05 after Bonferroni correction). Placebo treatment was associated with a significant decrease in activity only in the right amygdala, and no region had a change in activity that was correlated with change in depression scores. The groups differed significantly in the relationship between the changes in depression scores and in activity in the thalamus bilaterally and the left ventral striatum. The findings provide evidence that administration of supraphysiologic thyroid hormone improves depressive symptoms in patients with bipolar disorder by modulating function in components of the anterior limbic network.

Multi-centre calibration of an adaptive thresholding method for PET-based delineation of tumour volumes in radiotherapy planning of lung cancer.

PURPOSE: To evaluate the calibration of an adaptive thresholding algorithm (contrast-oriented algorithm) for FDG PET-based delineation of tumour volumes in eleven centres with respect to scanner types and image data processing by phantom measurements. METHODS: A cylindrical phantom with spheres of different diameters was filled with FDG realizing different signal-to-background ratios and scanned using 5 Siemens Biograph PET/CT scanners, 5 Philips Gemini PET/CT scanners, and one Siemens ECAT-ART PET scanner. All scans were analysed by the contrast-oriented algorithm implemented in two different software packages. For each site, the threshold SUVs of all spheres best matching the known sphere volumes were determined. Calibration parameters a and b were calculated for each combination of scanner and image-analysis software package. In addition, "scanner-type-specific" calibration curves were determined from all values obtained for each combination of scanner type and software package. Both kinds of calibration curves were used for volume delineation of the spheres. RESULTS: Only minor differences in calibration parameters were observed for scanners of the same type (Δa ≤4%, Δb ≤14%) provided that identical imaging protocols were used whereas significant differences were found comparing calibration parameters of the ART scanner with those of scanners of different type (Δa ≤60%, Δb ≤54%). After calibration, for all scanners investigated the calculated SUV thresholds for auto-contouring did not differ significantly (all p>0.58). The resulting sphere volumes deviated by less than -7% to +8% from the true values. CONCLUSION: After multi-centre calibration the use of the contrast-oriented algorithm for FDG PET-based delineation of tumour volumes in the different centres using different scanner types and specific imaging protocols is feasible.

Midbrain serotonin transporters in de novo and L-DOPA-treated patients with early Parkinson's disease--a [123 I]-ADAM SPECT study.

BACKGROUND: Dopaminergic availability is known to linearly decline in Parkinson's disease (PD). In contrast, temporal characteristics of serotonergic markers like the serotonin transporter (SERT) in relation to clinical staging of PD and dopaminergic cell loss are less clear. This study investigated SERT availability using [(123) I]-ADAM and single-photon emission tomography (SPECT) in drug-naive, de novo patients, i.e., in a PD stage where dopaminergic decline starts to lead to the occurrence of the characteristic motor symptoms. METHODS: Nine de novo patients with PD and 9 age-matched healthy controls were studied. Measurements were repeated after 3 months of levodopa treatment in patients with PD, and dopaminergic transporter (DAT) binding was examined at baseline using [(123) I]-FP-CIT SPECT. RESULTS: No alterations of SERT availability were found between groups, and neither correlation between SERT and DAT nor effects of levodopa treatment on SERT was found in patients with PD. CONCLUSIONS: These preliminary findings indicate that midbrain SERT is preserved in unmedicated patients at this early stage of PD, supporting the view that serotonergic decline temporally follows dopaminergic cell loss.

Physical aspects of scintigraphy-based dosimetry for nuclear medicine therapy.

In nuclear medicine therapy the treatment of tumours by radiation exposure from internally deposited labelled antibodies or labelled peptides is currently an active field of investigation. To permit the efficient delivery of high amounts of radiation dose to tumours while limiting the radiation dose to critical organs dosimetry calculations have to be performed. These are relying on scintigraphic data being input to the well known MIRD formalism. This paper focuses on the methods and the difficulties associated with the scintigraphic determination of organ kinetics. The physical properties of the well-known scintigraphic imaging modalities, PET, SPECT and planar scintigraphy, are discussed thereby taking into account the properties of the appropriate radionuclides currently being available for therapy and dosimetry. Several arguments are given and disputed for the limited clinical use of PET and SPECT in dosimetry and the ongoing preference of planar whole-body imaging as the method of choice. The quantitative restrictions still inherent to this method are also discussed in detail. Procedural recommendations are proposed covering all processes related to data acquisition, data correction and data analysis which finally lead to reliable estimations of organ dose.

123I-IMT SPECT for evaluation of the response to radiation therapy in high grade gliomas: a feasibility study.

Assessing response to radiation therapy in patients with high grade gliomas is needed upon making decisions toward further therapy strategies. Currently used standard imaging tools such as CT and MRI are not sensitive enough to detect early therapy effects. We prospectively investigated if single photon emission computed tomography (SPECT) using radiolabelled amino acid derivate (123)I-methyltyrosine (IMT) would be useful for this aim. 10 patients with histologically proven high grade gliomas, who were candidates for radiation therapy, were enrolled in this investigation. All patients were examined by IMT SPECT before radiation therapy and 4 weeks after the initiation of the hypofractionated application of 40 Gy. Patients were followed up for 39 months; the tumours to background ratios (T/B) for IMT under/before radiation therapy were correlated to survival times. Initially, SPECT depicted an abnormal intratumoural IMT uptake in all patients (mean T/B ratios 1.37-1.87). In four out of 10 patients, the mean T/B ratios decreased by more than 10% under radiation therapy. In six other patients, the BQ decreased by less than 10% or increased. There were no significant correlations between the degree of changes in T/B and survival (r = -0.1, p = 0.973). Serial IMT SPECT measurements allow detection of changes in amino acid accumulation in high-grade gliomas under radiation therapy. However, these changes seem to possess no prognostic value in respect to survival prediction.

Impact of FDG-PET/MRI image fusion on the detection of pancreatic cancer.

BACKGROUND: This study assessed the value of image fusion with (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) in patients suspected of having pancreatic cancer. METHODS: 32 patients (12 women, 20 men; age 24-79 years; mean 56.6 years) were included. All patients underwent whole-body FDG-PET examinations and contrast-enhanced MRI. Image fusion used a semiautomatic voxel-based algorithm. Separate reading, side-by-side analysis and evaluation of fused PET/MRI images were performed. Results were correlated to histopathology (n = 30), or clinical follow-up (n = 2). RESULTS: 15/32 patients had pancreas cancer and 17/32 patients benign disease. The sensitivity and specificity for cancer detection by FDG-PET were 93 and 41% for visual and 86 and 58% for semiquantitative analysis whereas MRI achieved 100 and 76% respectively. Topographical assignment of PET foci by image fusion was superior to side-by-side analysis in 11/39 (28%) foci (in 8/32 patients). However, a true impact on therapeutic strategy was observed only in 1/8 patients as the presence of multiple metastases, irresectable primaries or medical reasons for inoperability prevented a curative setting. CONCLUSION: Compared to side-by-side analysis, PET/MRI image fusion improves the anatomical assignment and interpretation of FDG foci. The therapeutic benefit for the patient however is limited in patients with multiple lesions or incurable primaries.

Thermovoltaic properties of hornet silk.

In silk from the larval silk caps of the Oriental hornet Vespa orientalis (Hymenoptera, Vespinae), temperature-dependent changes in the electric voltage have been recorded, with rise in the voltage occurring mainly upon rise in the temperature between 10-36 degrees C. The peak voltage was measured between 32-38 degrees C and attained 240-360 mV, but with further increase in temperature, the voltage decreased, dropping to 0 mV at about 45-50 degrees C. Upon second measurement (of same silk specimen), the voltage peak usually occurred later (by 8-9 degrees C) and at higher temperature than in the first measurement. Continuous measurements during warming up to 30 degrees C followed by cooling down to 15 degrees C yielded an hysteresis between the warming "line" and the cooling "line", the former often straight and the latter usually curved. Maintaining the silk specimen at a fixed temperature for a prolonged period (hours) initially causes the voltage to rise, then remain steady, and finally drop. Boiling the silk caps in tap water for 7-10 min exerts some changes in the silk properties, mainly a decrease in voltage level. The general behavior of the silk suggests that it is a polymer endowed with the qualities of an organic semiconductor. The various properties of the larval silk are discussed in great detail.

Image guided respiratory gated hypofractionated Stereotactic Body Radiation Therapy (H-SBRT) for liver and lung tumors: Initial experience.

To evaluate our initial experience with image guided respiratory gated H-SBRT for liver and lung tumors. The system combines a stereoscopic x-ray imaging system (ExacTrac X-Ray 6D) with a dedicated conformal stereotactic radiosurgery and radiotherapy linear accelerator (Novalis) and ExacTrac Adaptive Gating for dynamic adaptive treatment. Moving targets are located and tracked by x-ray imaging of implanted fiducial markers defined in the treatment planning computed tomography (CT). The marker position is compared with the position in verification stereoscopic x-ray images, using fully automated marker detection software. The required shift for a correct, gated set-up is calculated and automatically applied. We present our acceptance testing and initial experience in patients with liver and lung tumors. For treatment planning CT and Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) as well as magnetic resonance imaging (MRI) taken at free breathing and expiration breath hold with internal and external fiducials present were used. Patients were treated with 8-11 consecutive fractions to a dose of 74.8-79.2 Gy. Phantom tests demonstrated targeting accuracy with a moving target to within +/-1 mm. Inter- and intrafractional patient set-up displacements, as corrected by the gated set-up and not detectable by a conventional set-up, were up to 30 mm. Verification imaging to determine target location during treatment showed an average marker position deviation from the expected position of up to 4 mm on real patients. This initial evaluation shows the accuracy of the system and feasibility of image guided real-time respiratory gated H-SBRT for liver and lung tumors.

Evaluation of patients with liver metastases from colorectal cancer for locally ablative treatment with laser induced thermotherapy. Impact of PET with 18F-fluorodeoxyglucose on therapeutic decisions.

PURPOSE: Before locally ablative treatment of colorectal liver metastases, patients have to be carefully evaluated to decide whether this is the adequate therapy. In this study we determined the value of FDG-PET in comparison to conventional staging procedures. PATIENTS, METHODS: In 68 consecutive patients referred for laser induced thermotherapy (LITT) of liver metastases from colorectal cancer, pretherapeutic staging with conventional imaging (thoracic and abdominal CT, liver MRI, chest X-ray) and FDG-PET was performed. The examinations were analysed separately and blinded. Based on the staging information, therapeutic decisions were made by an interdisciplinary review board according to a standardized algorithm. The results were compared between conventional imaging and FDG-PET, and were validated by clinical follow up data and histopathology, respectively. RESULTS: On FDG-PET 210 lesions were interpreted as tumour manifestations. 48 of these were not seen on conventional imaging (true positive, n = 46). In contrast, 24 lesions were visualized by conventional imaging only (true positive, n = 12). Compared to conventional imaging, discrepant findings on FDG-PET led to treatment modifications in 25 patients (37%); these were correct in 20/25 patients. According to the actual treatment course, the inadequate treatment modifications in the remaining 5 patients were avoided by further diagnostic procedures (i.e. biopsies). CONCLUSION: In the evaluation of patients with known liver metastases from colorectal cancer before LITT, FDG-PET depicts relevant findings subsidiary to conventional imaging and thus is of high value for therapeutic decision making.

Corrections of arterial input function for dynamic H215O PET to assess perfusion of pelvic tumours: arterial blood sampling versus image extraction.

Assessment of perfusion with 15O-labelled water (H215O) requires measurement of the arterial input function (AIF). The arterial time activity curve (TAC) measured using the peripheral sampling scheme requires corrections for delay and dispersion. In this study, parametrizations with and without arterial spillover correction for fitting of the tissue curve are evaluated. Additionally, a completely noninvasive method for generation of the AIF from a dynamic positron emission tomography (PET) acquisition is applied to assess perfusion of pelvic tumours. This method uses a volume of interest (VOI) to extract the TAC from the femoral artery. The VOI TAC is corrected for spillover using a separate tissue TAC and for recovery by determining the recovery coefficient on a coregistered CT data set. The techniques were applied in five patients with pelvic tumours who underwent a total of 11 examinations. Delay and dispersion correction of the blood TAC without arterial spillover correction yielded in seven examinations solutions inconsistent with physiology. Correction of arterial spillover increased the fitting accuracy and yielded consistent results in all patients. Generation of an AIF from PET image data was investigated as an alternative to arterial blood sampling and was shown to have an intrinsic potential to determine the AIF noninvasively and reproducibly. The AIF extracted from a VOI in a dynamic PET scan was similar in shape to the blood AIF but yielded significantly higher tissue perfusion values (mean of 104.0 +/- 52.0%) and lower partition coefficients (-31.6 +/- 24.2%). The perfusion values and partition coefficients determined with the VOI technique have to be corrected in order to compare the results with those of studies using a blood AIF.

[Determination of ventricular volumes in coronary artery disease: comparison of two gated SPECT analysis tools with MRI]. / Bestimmung ventrikulärer Volumina bei koronarer Herzerkrankung: Vergleich zweier Gated-SPECT-Analyseverfahren mit MRT.

AIM: Comparison of two gated SPECT analysis tools -- gated SPECT quantification (GSQ) and emory cardiac toolbox (ECT) -- in patients with coronary artery disease (CAD) and severely impaired left ventricular function (preoperative: EF <35% by cardiac catheter). PATIENTS, METHODS: A total of 56 gated SPECT examinations (one-day hybrid-protocol with (201)Tl-chloride for rest and (99m)Tc-sestamibi for stress applied during low-dose dobutamine stress MR-examination; temporal resolution; 8 phases per cardiac cycle) were performed in 36 patients (31 preoperatively, 25 postoperatively) and compared with MRI in 48 cases. Left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes as well as the left ventricular ejection fraction (LV-EF) were calculated. RESULTS: The total volumetric assessment by both analysis algorithms (n = 56) showed good intraclass correlation coefficients preoperatively (n = 31), but even better postoperatively (n = 25). The mean reconstruction time was approximately 3 minutes ( +/- 2 SD) for GSQ and 15 minutes ( +/- 5 SD) for ECT. In comparison to MRI the results of both analysis tools also correlated well, but the agreement decreased in the presence of scared tissue. The mean LV-EF (MRI) preoperatively was 30.4%, in 6/36 patients above the values calculated from cardiac catheter, postoperatively 34.6%. CONCLUSION: Both gated SPECT analysis tools showed reliable volumetric assessments in high-risk patients with CAD and severely reduced LV-EF in comparison to MRI, with advantages for GSQ in terms of postprocessing time. However, for the calculation of LV-EF a markedly lower concordance with MR-results was observed for both methods depending on the presence of myocardial scars.

Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand [123I]-ADAM.

We studied the midbrain SERT availability in patients with major depression and assessed the relation of SERT occupancy by citalopram to the treatment response. 21 non-medicated patients with major depression and 13 healthy controls were examined by [(123)I]-ADAM SPECT. The midbrain SERT availability (SERT V(3)'') was calculated using individual MRI scans. In 13/21 patients SPECT was repeated 7 days after oral medication with citalopram (10 mg/day). We found no significant difference in the mean midbrain SERT availability between the studied patients with major depression and healthy controls (0.86 +/- 0.27 vs. 0.71 +/- 0.44, p = 0.069). The mean SERT occupancy accounted to 61%. The degree of SERT blockade by citalopram did not correlate with the reduction in HAMD total score. Treatment with low-dosed citalopram caused individually variable occupancy of the midbrain-SERT and a rapid clinical improvement in 54% of the investigated patients.

Colon dissection: a new three-dimensional reconstruction tool for computed tomography colonography.

PURPOSE: To improve the sensitivity of computed tomography (CT) colonography in the detection of polyps by comparing the 3D reconstruction tool "colon dissection" and endoluminal view (virtual colonoscopy) with axial 2D reconstructions. MATERIAL AND METHODS: Forty-eight patients (22 M, 26 F, mean age 57 +/- 21) were studied after intra-anal air insufflation in the supine and prone positions using a 16-slice helical CT (16 x 0.625 mm, pitch 1.7; detector rotation time 0.5 s; 160 mAs und 120 kV) and conventional colonoscopy. Two radiologists blinded to the results of the conventional colonoscopy analyzed the 3D reconstruction in virtual-endoscopy mode, in colon-dissection mode, and axial 2D slices. RESULTS: Conventional colonoscopy revealed a total of 35 polyps in 15 patients; 33 polyps were disclosed by CT methods. Sensitivity and specificity for detecting colon polyps were 94% and 94%, respectively, when using the "colon dissection", 89% and 94% when using "virtual endoscopy", and 62% and 100% when using axial 2D reconstruction. Sensitivity in relation to the diameter of colon polyps with "colon dissection", "virtual colonoscopy", and axial 2D-slices was: polyps with a diameter >5.0 mm, 100%, 100%, and 71%, respectively; polyps with a diameter of between 3 and 4.9 mm, 92%, 85%, and 46%; and polyps with a diameter < 3 mm, 89%, 78%, and 56%. The difference between "virtual endoscopy" and "colon dissection" in diagnosing polyps up to 4.9 mm in diameter was statistically significant. CONCLUSION: 3D reconstruction software "colon dissection" improves sensitivity of CT colonography compared with the endoluminal view.

Myocardial viability assessment in patients with highly impaired left ventricular function: comparison of delayed enhancement, dobutamine stress MRI, end-diastolic wall thickness, and TI201-SPECT with functional recovery after revascularization.

This study compared different magnetic resonance imaging (MRI) methods with Tl(201) single photon emission computerized tomography (SPECT) and the "gold standard" for viability assessment, functional recovery after coronary artery bypass grafting (CABG). Twenty patients (64+/-7.3 years) with severely impaired left ventricular function (ejection fraction [EF] 28.6+/-8.7%) underwent MRI and SPECT before and 6 months after CABG. Wall-motion abnormalities were assessed by stress cine MRI using low-dose dobutamine. A segment with a nonreversible defect in Tl(201)-SPECT and a delayed enhancement (DE) in an area >50% of the entire segment, as well as an end-diastolic wall thickness <6 mm, was defined as nonviable. The mean postoperative EF (n=20) improved slightly from 28.6+/-8.7% to 32.2+/-12.4% (not significant). Using the Tl(201)-SPECT as the reference method, end-diastolic wall thickness, MRI-DE, and stress MRI showed high sensitivity of 94%, 93%, and 84%, respectively, but low specificities. Using the recovery of contractile function 6 months after CABG as the gold standard, MRI-DE showed an even higher sensitivity of 99%, end-diastolic wall thickness 96%, stress MRI 88%, and Tl(201)-SPECT 86%. MRI-DE showed advantages compared with the widely used Tl(201)-SPECT and all other MRI methods for predicting myocardial recovery after CABG.

Imaging of dopamine transporters and D2 receptors in vascular parkinsonism: a report of four cases.

The role of nuclear medicine imaging in the diagnosis of vascular parkinsonism (VP) has been addressed by only few studies up to now. Most previous reports suggest no or only mild impairment of DAT and D2 receptors in VP. In contrast, in four patients with VP, reported here, the combined DAT and D2 receptor SPECT showed highly unusual changes in the pre- and/or postsynaptic dopaminergic system. The possible value of combined DAT/D2 receptor SPECT imaging should be investigated by future prospective studies.

Bedside microdialysis reflects dysfunction of cerebral energy metabolism in patients with aneurysmal subarachnoid hemorrhage as confirmed by 15 O-H2 O-PET and 18 F-FDG-PET.

OBJECTIVE: To compare microdialysis (MD) and positron emission tomography (PET) in the detection of ischemia in aneurysmal subarachnoid hemorrhage (SAH) patients. METHODS: 15 SAH patients (13F/2M, 48+/-13 years, WFNS Grade I-V) were prospectively included in the study. A MD-catheter was inserted into the brain parenchyma most likely to be affected by vasospasm directly after aneurysm clipping. Glucose, pyruvate, lactate, glutamate and glycerol were analyzed hourly (CMA 600). 15O-H2O-PET scans (n=10) and 18F-FDG-PET scans (n=13) were performed between the day 2 and 17 after SAH. 15O-H2O-PET data were merged with CT scans to provide quantification of rCBF within the MD-ROI (rCBFMD; Amira, ZIB Berlin, Germany). 18F-FDG-PET data were evaluated visually by visual analysis. RESULTS: Regions of glucose hypometabolism were observed in 10 patients with symptoms of ischemia. Their rCBF was lower compared to asymptomatic patients (p<0.05). The MD levels of glutamate, lactate, the L/P ratio and glycerol were significantly higher in symptomatic than asymptomatic patients (p<0.05). Out of all measured MD parameters, glutamate showed the closest correlation with rCBF (r=-0.66, p=0.014). Microdialysis parameters were well correlated with glucose hypometabolism (18F-FDG-PET) and symptoms of ischemia. However, the threshold for a metabolic derangement was above the limits of cerebral ischemia defined by PET. CONCLUSION: MD is a useful tool to monitor ischemia, especially in patients with high-grade SAH.

Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients.

72 consecutive patients with suspected parkinsonian syndromes (PS) were studied by dopamine transporter (DAT) and D2 receptor SPECT in order to evaluate the accuracy of combined SPECT imaging. In the follow-up, the patients were diagnosed as having Parkinson's disease (PD, n = 25), dementia with Lewy bodies (DLB, n = 6), multiple system atrophy (MSA, n = 13), progressive supranuclear palsy (PSP, n = 8), corticobasal degeneration (CBD, n = 9), and essential tremor (ET, n = 11). Using the iteratively estimated optimal cutoffs, DAT was reduced in 57/61 PS patients, whereas all ET patients were identified as "normal". Reduced D2 receptor binding had 7/13 patients with MSA, 6/8 patients with PSP, 2/9 patients with CBD and no ET, PD or DLB patients. FP-CIT SPECT allows an accurate detection of nigrostriatal affection in neurodegenerative PS. IBZM SPECT is useful to approve the diagnosis of PSP and MSA although a normal finding cannot exclude an atypical PS. IBZM SPECT seems to be of restricted value in CBD.

Early age of onset in fatal familial insomnia. Two novel cases and review of the literature.

Fatal familial insomnia (FFI) is a prion disease exhibiting the PRNP D178N/129M genotype. Features of this autosomal dominant illness are progressive insomnia, dysautonomia, myoclonus, cognitive decline and motor signs associated with thalamic nerve cell loss and gliosis. In contrast to the new variant of Creutzfeldt-Jakob disease (vCJD) the onset of FFI is in middle to late adulthood. We report two male patients who belong to a large German FFI kindred. They were examined clinically, and postmortem neuropathological examination was carried out in collaboration with the German reference centre for prion disease. Additionally, the prion protein gene (PRNP) was analysed. To identify further patients with disease onset under 30 years of age a comprehensive literature review was carried out. Two male patients presented with typical symptoms of FFI at the age of 23 and 24 years. In their kindred, the age of onset has never before been under 44 years of age. Our literature review identified five additional early onset cases who died at age 21 to 25 years. In all 22 reviewed FFI families the median manifestation age was 49.5 years. Although phenotypic variability of FFI is common, age of onset under 30 years has been considered to be a hallmark of vCJD with a mean manifestation at 27 years of age. Our findings underline that in addition to vCJD, FFI must be considered in cases of young-onset prion disease. This has considerable impact on clinical management and genetic counselling.