Incremental value of amyloid-PET versus CSF in the diagnosis of Alzheimer's disease.

PURPOSE: To compare the incremental diagnostic value of amyloid-PET and CSF (Aß42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm. METHODS: Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker. RESULTS: Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3. CONCLUSIONS: Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence. TRIAL REGISTRATION: EudraCT no.: 2014-005389-31.

Radiofrequency ablation for non-spinal osteoid osteomas in 557 patients.

OBJECTIVES: To present the results of biopsy and computed tomography (CT) guided radiofrequency ablation (RFA) for non-spinal osteoid osteomas, and compare the results before and after procedural modifications. METHODS: We retrospectively studied 557 patients with non-spinal osteoid osteomas treated with biopsy and CT-guided RFA. In 68 patients we used 3-mm CT at 2-mm intervals, 19 G/5-mm active tip electrodes, and one 4-minute ablation at 90-93°C. In 489 patients we used contiguous 1-mm CT, 20 G/5-15-mm electrodes, ablation maintaining 60°C for 2 min followed by 14-15 min at 90-93°C, and multiple ablations in the same session for large and multiform lesions. RESULTS: 533/557 patients (96%) remained asymptomatic and 24/557 (4%) had recurrence; repeat RFA was successful in 22/24 patients (92%). Biopsy was non-diagnostic in 82%. With the modifications performed, success improved from 79% to 98%, recurrences reduced from 21% to 2% and complications from 5.9% to 0.2% (p < 0.001). All patients with large and multiform lesions treated with one ablation had recurrence, compared to no patient with similar lesions and multiple ablations in the same session. CONCLUSION: Electrode parameters, duration of ablation, morphology and size of osteoid osteomas are important for RFA. The above modifications are recommended for improved outcome.

(111)In-pentetreotide SPET/CT in carcinoid tumours: is the role of hybrid systems advantageous in abdominal or thoracic lesions?

Our aim was to evaluate the different clinical value of (111)In-pentetreotide hybrid SPET/CT versus SPET alone in detecting carcinoid tumours located in the thoracic and abdominal region. Twenty-four patients with carcinoid tumours histologically proven (13 of abdominal origin, 11 of thoracic origin) underwent (111)In-pentetreotide SPET/CT with hybrid system (Millennium VG with Hawkeye, G.E.M.S., USA) composed of a dual head gamma camera equipped with a low dose X-ray tube. Single photon emission tomography images were performed 4h and 24h after (111)In-pentetreotide intravenous administration, while SPET/CT co-registered images were performed at 4h. Scintigraphic images were first evaluated alone and then re-interpreted by adding transmission fused data. Nine of the 13 patients with tumours of abdominal origin showed pathological SPET images, while 4/13 were negative. Seven out of the 11 patients with tumour of thoracic origin had pathological SPET findings, while 4/11 were negative. In all, 11/24 subjects disclosed abdominal pathological uptake and 10/24 thoracic. In 6/11 abdominal cases SPET/CT allowed anatomical localization of lesions, while in 2/10 in thoracic cases. Additional data were provided by SPET/CT in 8/24 cases (6 abdominal, 2 thoracic), by transmission images characterized as lesions not expressing somatostatin receptors. Sensitivity of SPET alone in all carcinoids was 72%, negative predictive value (NPV) was 50% and accuracy was 78%. Considering abdominal lesions (independently of the origin) sensitivity of SPET alone was 64.7%, NPV was 40%, accuracy was 71.4%. For thoracic lesions sensitivity of SPET alone was 83.3%, NPV was 66.7% and accuracy was 87.5%. For SPET/CT considering together all carcinoids and also separately lesions of abdominal and of thoracic origin, sensitivity, NPV and accuracy were always 100%. In conclusion, SPET/CT imaging was more useful to anatomically detect carcinoids either in abdomen or in thorax and specifically lesions not expressing somatostatin receptors, as compared to SPET alone.

Semi-quantitative analysis of perfusion of Brodmann areas in the differential diagnosis of cognitive impairment in Alzheimer's disease, fronto-temporal dementia and mild cognitive impairment.

Different perfusion defects reflect neurological damage characteristics of different kinds of dementia. Our aim was to investigate the role of brain single photon emission tomography (SPET) with semiquantitative analysis of Brodmann areas in dementia, by technetium-99m - hexamethyl-propylenamine- oxime ((99m)Tc-HMPAO) brain SPET with semiquantitative analysis of Brodmann areas in patients with Alzheimer's disease (AD), frontotemporal dementia (FTD) and mild cognitive impairment (MCI). We studied 75 patients, 25 with AD (NiNCDS ADRDA criteria), 25 with FTD (Lund and Manchester criteria), 25 with MCI (EADC criteria). After i.v. injection of 740MBq of (99m)Tc-HMPAO, each patient underwent brain SPET. A software application was used able to map the SPET brain image to a stereotaxic atlas (Talairach), providing an affine co-registration by blocks of data defined in the Talairach space. A normal database calculating voxel by voxel the mean and the standard deviation of the measured values was built. Functional SPET data of 3D regions of interest (ROI) of predefined Brodmann's area templates were compared with those of a database of healthy subjects of the same age and gender. Mean values obtained in the Brodmann area ROI in the different groups of patients studied were evaluated. Our results showed that different Brodmann areas were significantly impaired in the different categories of dementia subjects. Both areas 37 (temporal gyrus) and 39 (angular gyrus) of AD patients (mean+/-SD: 37L= -1.6+/-1.0; 37R= -1.5+/-1.1; 39L= -2.3+/-1.3; 39R= -1.9+/-1.2) showed significant hypoperfusion (P<0.05) versus MCI (37L= -0.9 +/-0.7; 37R= -1.1+/-0.9; 39L= -1.4+/-1.1; 39R= -1.6+/-1.6.) and FTD (37L= -1.1+/-0.8; 37R= -1.0+/-0.9; 39L= -1.4+/-1.0; 39R= -1.2+/-1.2) subjects. AD patients showed significantly (P<0.01) decreased perfusion in areas 40 (supramarginal gyrus) (40L= -2.6+/-1.0; 40R= -2.3+/-1.1) with respect to MCI patients (40L= -1.8+/-0.9; 40R= -1.7+/-1.2). Finally, FTD patients showed significant hypoperfusion (P<0.05) in both areas 47 (frontal association cortex) (47L= -1.8+/-0.8; 47R= -1.1+/-0.8) in comparison with MCI subjects (47L= -1.2+/-0.9; 47R= -0.9+/-0.9). In conclusion, our results suggest that semiquantitative analysis of single Brodmann areas identify frontal area hypoperfusion in FTD patients and also parietal and temporal impairment in AD patients. In MCI patients, no hypoperfusion pattern is identified.

Reciprocal Incremental Value of 18F-FDG-PET and Cerebrospinal Fluid Biomarkers in Mild Cognitive Impairment Patients Suspected for Alzheimer's Disease and Inconclusive First Biomarker.

BACKGROUND: In Alzheimer's disease (AD) diagnosis, both cerebrospinal fluid (CSF) biomarkers and FDG-PET sometimes give inconclusive results. OBJECTIVE: To evaluate the incremental diagnostic value of FDG-PET over CSF biomarkers, and vice versa, in patients with mild cognitive impairment (MCI) and suspected AD, in which the first biomarker resulted inconclusive. METHODS: A consecutive series of MCI patients was retrospectively selected from two Memory Clinics where, as per clinical routine, either the first biomarker choice is FDG-PET and CSF biomarkers are only used in patients with uninformative FDG-PET, or vice versa. We defined criteria of uncertainty in interpretation of FDG-PET and CSF biomarkers, according to current evidence. The final diagnosis was established according to clinical-neuropsychological follow-up of at least one year (mean 4.4±2.2). RESULTS: When CSF was used as second biomarker after FDG-PET, 14 out of 36 (39%) received informative results. Among these 14 patients, 11 (79%) were correctly classified with respect to final diagnosis, thus with a relative incremental value of CSF over FDG-PET of 30.6%. When FDG-PET was used as second biomarker, 26 out of 39 (67%) received informative results. Among these 26 patients, 15 (58%) were correctly classified by FDG-PET with respect to final diagnosis, thus with a relative incremental value over CSF of 38.5%. CONCLUSION: Our real-world data confirm the added values of FDG-PET (or CSF) in a diagnostic pathway where CSF (or FDG-PET) was used as first biomarkers in suspected AD. These findings should be replicated in larger studies with prospective enrolment according to a Phase III design.

Cerebrospinal fluid neuron-specific enolase: a further marker of Alzheimer's disease?

To investigate whether neuron-specific enolase (NSE) plays a role in dementia, we measured cerebrospinal fluid (CSF) concentrations of NSE, Abeta42 and total protein tau (h-tau) in different dementia patients. We studied 159 patients: 76 with Alzheimer's disease (AD), 35 with mild cognitive impairment (MCI), 28 with frontotemporal dementia (FTD), and 20 with Lewy body disease (LBD). Thirty healthy age-matched subjects were studied as controls. NSE was measured by immunoradiometric assay, Abeta42 and h-tau were dosed by ELISA assay. Mean CSF NSE was significantly higher in AD (15.1+/-9.9 ng/ml) than in controls (8.3+/-3.5 ng/ml, p<0.01), FTD (9.1+/-6.1 ng/ml, p<0.05) and MCI (9.7+/-7.8 ng/ml, p<0.05). Ab42 was significantly lower in AD (413.8+/-163.7 pg/ml) than in MCI (708.4+/-422.1 pg/ml, p<0.001) and controls (914.4+/-277.1 pg/ml, p<0.05); it was also significantly reduced in FTD (497.1+/-221.9 pg/ml) versus MCI (p<0.05) and controls (p<0.001); and in LBD patients (477.1+/-225.7 pg/ml) compared with MCI (p<0.05) and controls (p<0.001). H-tau concentration was significantly higher in AD (607.9+/-372.3 pg/ml, p<0.001) than in MCI (383.8+/-277.9 pg/ml, p<0.05), controls (176.6+/-43.9 pg/ml, p<0.001) and LBD (472.3+/-357.7 pg/ml, p<0.05); it was also increased in FTD (541.76+/-362.8 pg/ml) versus contro s (176.6+/-43.9 pg/ml, p<0.001). Furthermore, NSE was inversely correlated with Ab42 (r=-0.333, p=0<0001) and directly correlated with h-tau (r=0.370, p=0<0001). In conclusion, CSF NSE emerged as a specific indicator of AD and showed the same behaviour as the other accepted markers of AD, being correlated with both biomarkers.

Vaginal metastasis of a Ewing Sarcoma five years after resection of the primary tumor.

A 35-year-old female presented with pain and swelling of the left wrist. A diagnosis of Ewing sarcoma was made and she underwent neoadjuvant chemotherapy and surgery. Macroscopic viable areas remained on the map of the surgical specimen; as such, she was classified as a poor responder and received high dose adjuvant chemotherapy. She remained disease-free for five years, until age 40. A vaginal polyp was then detected during a routine gynaecologic examination. It was removed and histopathology revealed metastatic Ewing sarcoma. To our knowledge, this is the first reported case of a vaginal metastasis of Ewing sarcoma.

Parosteal osteosarcoma mimicking osteochondroma: A radio-histologic approach on two cases.

BACKGROUND: Parosteal osteosarcoma is a well-differentiated variant of osteosarcoma that affects the surface of the bone. The imaging pattern is very typical. We report two cases mimicking an osteochondroma, radiologically and histologically and propose an explanation. METHODS: The review of 86 parosteal osteosarcomas of bone revealed this atypical pattern only once. A consultation case was received in the same time, and added to ours. Patients were 28 years old and 56 years old females. Imaging studies included two radiographs, two CTscans, one MRI examination and one bone scan and the results were compared to histology. RESULTS: On imaging, both lesions presented as ossified lobulated masses attached with a broad base to the underlying cortex. No radiolucent cleft separated the masses and the host bone and cortex continuity between the mass and the femur was seen, with medullary communication. The marrow of the mass had a different density and intensity compared to normal marrow. So, there were features of an osteochondroma (cortex and medullary continuity) and of a parosteal osteosarcoma (ossified marrow). Pathological assessment on the final specimen confirmed the presence of low-grade parosteal osteosarcomas, after an erroneous diagnosis of osteochondroma on the initial biopsy. CONCLUSIONS: Parosteal osteosarcoma can be rarely confused with osteochondroma. A radiologic-pathologic correlation is essential. Cortex continuity is the most misleading imaging feature that may occur in parosteal osteosarcomas. A knowledge of this misleading pattern will help diagnose the lesion from the beginning.

Percutaneous CT-guided biopsy of the musculoskeletal system: results of 2027 cases.

INTRODUCTION: Biopsy of the musculoskeletal system is useful in the management of bone lesions particularly in oncology but they are often challenging procedures with a significant risk of complications. Computed tomography (CT)-guided needle biopsies may decrease these risks but doubts still exist about their diagnostic accuracy. This retrospective analysis of the experience of a single institution with percutaneous CT-guided biopsy of musculoskeletal lesions evaluates the results of these biopsies for bone lesions either in the appendicular skeleton or in the spine, and defines indications. MATERIALS AND METHODS: We reviewed the results of 2027 core needle biopsies performed over the past 18 years at the authors' institution. The results obtained are subject of this paper. RESULTS: In 1567 cases the correct diagnosis was made with the first CT-guided needle biopsy (77.3% accuracy rate), in 408 cases the sample was not diagnostic and in 52 inadequate. Within 30 days these 408 patients underwent another biopsy, which was diagnostic in 340 cases with a final diagnostic accuracy of 94%. Highest accuracy rates were obtained in primary and secondary malignant lesions. Most false negative results were found in cervical lesions and in benign, pseudotumoral, flogistic, and systemic pathologies. There were 22 complications (18 transient paresis, 3 haematomas, 1 retroperitoneal haematoma) which had no influence on the treatment strategy, nor on patient outcome. CONCLUSION: This technique is reliable and safe and should be considered nowadays the gold standard for biopsies of the musculoskeletal system.