Oculomotor Dysfunction in Idiopathic and LRRK2-Parkinson's Disease and At-Risk Individuals.

Background: Video-oculography constitutes a highly-sensitive method of characterizing ocular movements, which could detect subtle premotor changes and contribute to the early diagnosis of Parkinson's disease (PD). Objective: To investigate potential oculomotor differences between idiopathic PD (iPD) and PD associated with the G2019S variant of LRRK2 (L2PD), as well as to evaluate oculomotor function in asymptomatic carriers of the G2019S variant of LRRK2. Methods: The study enrolled 129 subjects: 30 PD (16 iPD, 14 L2PD), 23 asymptomatic carriers, 13 non-carrier relatives of L2PD patients, and 63 unrelated HCs. The video-oculographic evaluation included fixation, prosaccade, antisaccade, and memory saccade tests. Results: We did not find significant differences between iPD and L2PD. Compared to controls, PD patients displayed widespread oculomotor deficits including larger microsaccades, hypometric vertical prosaccades, increased latencies in all tests, and lower percentages of successful antisaccades and memory saccades. Non-carrier relatives showed oculomotor changes with parkinsonian features, such as fixation instability and hypometric vertical saccades. Asymptomatic carriers shared multiple similarities with PD, including signs of unstable fixation and hypometric vertical prosaccades; however, they were able to reach percentages of successful antisaccade and memory saccades similar to controls, although at the expense of longer latencies. Classification accuracy of significant oculomotor parameters to differentiate asymptomatic carriers from HCs ranged from 0.68 to 0.74, with BCEA, a marker of global fixation instability, being the parameter with the greatest classification accuracy. Conclusions: iPD and LRRK2-G2019S PD patients do not seem to display a differential oculomotor profile. Several oculomotor changes in asymptomatic carriers of LRRK2 mutations could be considered premotor biomarkers.

The usefulness of 18F-FDG-PET/CT in detecting musculoskeletal and vascular involvement in patients with polymyalgia rheumatica receiving glucocorticoids.

OBJECTIVE: Fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT is a promising diagnostic tool for polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV). PET/CT performance is recommended before the onset of steroid therapy because glucocorticoids (GC) may decrease the intensity of FDG uptake. However, this is not always possible in clinical practice. Our aim was to assess if PET/CT could be also useful to detect musculoskeletal and vascular involvement in patients receiving GC. METHODS: Single-center study of patients with PMR diagnosis based on 2012 EULAR/ACR criteria who underwent a PET/CT scan due to LVV suspicion. We compared the musculoskeletal and vascular FDG uptake between two groups: (a) steroid-naïve and (b) steroid-resistant patients. A sub-analysis was conducted in patients who were receiving GC to discern if the cumulative prednisone dose influences the FDG uptake. RESULTS: We evaluated 75 patients (27 men/ 48 women); mean age±SD: 68.2 ± 10.7 years. PET/CT was performed in 14 steroid-naïve and 61 steroid-resistant patients. Patients under GC had received a median cumulative prednisone dose of 1.8 [0.6-3.9] g. The pattern of musculoskeletal FDG uptake was similar in steroid-naïve and steroid-resistant patients. FDG uptake in the vessel wall was more frequently detected in steroid-naïve patients. However, PET/ CT was also useful to detect LVV in 62.3 % of the patients who were receiving GC. The percentage of patients who had positive PET/CT scans tended to decrease with higher cumulative prednisone doses. CONCLUSION: Even though GC therapy may decrease the 18-FDG uptake, PET/CT continues to be a useful tool to detect musculoskeletal and LVV involvement in PMR.

Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in a Giant Left Pectoral Muscle Plasmacytoma and Multiple Myeloma Case.

Extramedullary plasmacytoma is an unusual manifestation in multiple myeloma (MM). It can present as a solitary bone lesion and/or soft-tissue mass. Plasmacytoma can be presented at any location, but it is more common in the head and neck, usually without systemic involvement. The presence of plasmacytoma in MM is a predictor of rapidly progressive disease. The value of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (PET-FDG) is increasing, in the diagnosis, detection of occult lesions, and therapeutic monitoring. We describe a patient with rapidly-progressive, refractory, left pectoral muscle plasmacytoma and MM. A PET-FDG guided the therapy and allowed to identify the presence of disease relapse.

A 5-year longitudinal evaluation in patients with mild cognitive impairment by 11C-PIB PET/CT: a visual analysis.

OBJECTIVE: The aim of this study was to evaluate the cerebral amyloid distribution in patients with mild cognitive impairment (MCI), assessed by carbon-11-Pittsburgh compound B (C-PIB) PET/CT, after 5 years of follow-up. PATIENTS AND METHODS: Ten amnestic MCI (A-MCI) and four nonamnestic (NA-MCI) patients were studied by C-PIB PET/CT and re-evaluated 5 years later by a new C-PIB PET/CT. PET/CT scans were acquired 60-90 min after the administration of 555 MBq C-PIB and analyzed visually, to obtain a score of the cerebral cortical C-PIB retention in the frontal, basal ganglia (BG), temporoparietal (TP), occipital, posterior cingulate, and cerebellum areas. Initial and 5-year follow-up C-PIB retentions were compared. RESULTS: Initially, 9/10 A-MCI patients were C-PIB positive and one was C-PIB negative. All four NA-MCI patients were C-PIB negative. Of the C-PIB-positive A-MCI patients, seven progressed to Alzheimer's disease dementia (AD-D), one to mixed dementia and one remained as A-MCI. The C-PIB-negative A-MCI patient remained as A-MCI. Of the four C-PIB-negative NA-MCI, one progressed to semantic dementia. All changes in C-PIB retention were of low intensity. The A-MCI patients who progressed to AD-D (n=7) showed an increase in C-PIB retention in the frontal (5/7), BG (3/7), TP (3/7), occipital (1/7), and posterior cingulate (1/7) regions. The A-MCI patient who progressed to mix dementia showed an increase in C-PIB retention in the frontal region. The C-PIB-positive A-MCI patient who remained as A-MCI showed an increase in C-PIB retention in the frontal, BG, and TP areas. The amyloid deposition in the anterior part of the brain (frontal, TP, and BG) increased more than that in the posterior part (occipital and precuneus) (7/9 vs. 2/9; P<0.05). CONCLUSION: PIB retention increased predominantly in the frontal, BG, and TP areas. C-PIB-positive A-MCI patients mostly progressed to AD-D, showing similar topographic changes in their cerebral C-PIB pattern than the patient who remained as A-MCI.

Effect of positive carbon-11-choline PET/CT results in the therapeutic management of prostate cancer biochemical relapse.

OBJECTIVE: Carbon-11-(C)-choline PET/computed tomography (CT) has shown good results in re-staging of prostate cancer (PCa) with raised serum levels of prostate-specific antigen. Our aim was to evaluate the effect of positive C-choline PET/CT results in the therapeutic management of patients with PCa with biochemical relapse (BR) after curative intention treatment. PATIENTS AND METHODS: A total of 112 patients with PCa BR and positive C-choline PET/CT were retrospectively evaluated. PET/CT was acquired 20 min after intravenous administration of 555-740 MBq of C-choline. The therapeutic management after C-choline PET/CT was obtained from the clinical records. The minimum follow-up time was 18 months. RESULTS: In 80 (71.4%) of 112 patients, C-choline PET/CT showed local recurrence of PCa; in 17 (15.2%) patients, distant recurrence; and in 15 (13.4%) patients, local plus distant recurrence. A second malignancy was detected in five (4.5%) patients. The planned therapeutic management was changed as per positive C-choline PET/CT result in 74 (66.1%) patients and were treated as follows: 31 (27.7%) patients with HT, combined with other treatments in eight (7.1%), 17 (15.2%) with BT, 13 (11.6%) with external beam radiotherapy, one (0.9%) with RP, and four (3.6%) with chemotherapy. Treatment approach was not modified in 37 (33%) patients. No data was available from one (0.9%) patient. CONCLUSION: Positive C-choline PET/CT result had an important effect in the therapeutic management of patients with PCa and BR, leading to a change in the planned approach in two (66.1%) out of three patients. In addition, in 4.5% of the patients, the C-choline PET/CT allowed the detection of a second malignancy.

18F-FDG PET/CT in the follow-up of large-vessel vasculitis: A study of 37 consecutive patients.

OBJECTIVE: 18F-FDG PET/CT has proved to be of potential value for early diagnosis of large-vessel vasculitis (LVV), which frequently involves the aorta. However, its role in the follow-up of these patients has not been well established. Our aim was to evaluate the contribution of 18F-FDG PET/CT in this clinical situation. METHODS: This study included 37 consecutive patients (28 women, 66.5 ± 9.9 years) with an initial 18F-FDG PET/CT positive for LVV and a mean ± standard deviation follow-up PET/CT of 7.5 ± 2.9 months after the initial scan. A semiquantitative analysis of aortic wall uptake was performed calculating the target-to-background ratio (TBR: aortic wall uptake divided by blood pool uptake). The initial and follow-up TBR as well as the clinical and laboratory outcome were compared. RESULTS: Overall, the mean TBR decreased from 1.7 ± 0.5 at the initial scan to 1.5 ± 0.3 at the time of follow-up (p = 0.0001). In the 21 patients who experienced clinical improvement following therapy the TBR also decreased from 1.8 ± 0.6 to 1.5 ± 0.3 (p = 0.0002). However, in the other 16 patients, in whom the treating physician considered that there was no clinical improvement following therapy, no statistically significant differences in TBR were found when data from the first and the follow-up PET/CT scans were compared (1.6 ± 0.3 versus 1.5 ± 0.3, p = 0.1416). Patients who experienced clinical improvement following therapy showed a nonstatistically significant higher TBR at the time of disease diagnosis (1.8 ± 0.6 versus 1.6 ± 0.3; p = 0.12). CONCLUSIONS: The results obtained in the present study highlight the impact of 18F-FDG PET/CT on the management of patients with LVV.

Value of the visual and semiquantitative analysis of carbon-11-methionine PET/CT in brain tumors' recurrence versus post-therapeutic changes.

To compare the visual and semiquantitative analysis of carbon-11-methionine (C-MET) PET/computed tomography (CT) images in patients with primary brain tumors and suspected recurrence, persistence, or necrotic post-therapeutic changes. A total of 41 consecutive C-MET-PET/CT scans on 35 (21 men, mean age 44.1±16.6 years) patients were requested for MRI suspicion of recurrent or persistent primary tumor after therapy. The C-MET PET/CT were obtained 20 min after an intravenous injection of 555-740 MBq (15-20 mCi) of C-MET. Both visual and semiquantitative evaluations were performed comparing C-MET uptake between suspicious areas and different lesion/normal-to-background ratios. The final diagnosis was established by histological examination in 12 cases and clinical and MRI follow-up in 29 cases. Visual analyses were positive in 27 (63.4%) and negative in 14 (36.6%) of the C-MET PET/CT. The sensitivity was 83.9%, specificity was 90.0%, positive predictive value was 96.3%, negative predictive value was 64.3% and accuracy was 71.4%. For the semiquantitative analysis, all the lesion/normal-to-background ratios could differentiate between tumor and nontumor (P<0.001), the lesion/contralateral parenchyma (L/CP) maximum standardized uptake value (SUVmax) being the index with the highest area under de curve (0.938). Applying an L/CP SUVmax index of 1.21, the sensitivity was 89.3%, specificity was 90.0%, positive predictive value was 96.1%, negative predictive value was 75%, and accuracy was 82.9%. C-MET-PET/CT was a useful technique to differentiate post-therapeutic changes from tumor presence in treated patients with brain neoplasm in whom cerebral MRI is nonconclusive, showing a high diagnostic performance. Our results showed only slight differences between visual analysis methods and the L/CP SUVmax ratio, the best of the semiquantitative methods.

Amyloid imaging with (11)C-PIB PET/CT and glucose metabolism with (18)F-FDG PET/CT in a study on cognitive impairment in the clinical setting.

OBJECTIVE: The objective of this study was to evaluate the contribution of amyloid imaging with (11)C-Pittsburgh compound B ((11)C-PIB) and of glucose metabolism on F-fluorodeoxyglucose ((18)F-FDG) PET/CT to the study of cognitive impairment in the clinical setting. PATIENTS AND METHODS: Thirty-four patients (15 male, 19 female) were enrolled in the study. They were classified according to their clinically presented symptoms. Six patients had subjective memory complaints, five had nonamnestic mild cognitive impairment (MCI), seven had amnestic MCI, seven had prodromal Alzheimer's disease (AD), five had frontotemporal dementia, two had dementia with Lewy bodies, and two had cortical degeneration. All the scans were conducted to determine the likelihood of AD or to differentiate between AD and other dementia. Static 30-min (11)C-PIB and 15-min (18)F-FDG PET/CT scans were obtained. A visual analysis of images was performed. RESULTS: Three of the six patients with subjective memory complaints had positive (11)C-PIB scans and one of them also had (18)F-FDG hypometabolism. All five nonamnestic MCI patients had normal (11)C-PIB and (18)F-FDG. Four of the seven amnestic MCI patients showed (11)C-PIB cortical retention but only one had positive (18)F-FDG. Positive (11)C-PIB and (18)F-FDG were detected in five of the seven prodromal AD patients. All the five patients with FDT had positive (18)F-FDG scans, but only one of the five had (11)C-PIB cortical retention. Both dementia with Lewy bodies and cortical degeneration patients had positive (11)C-PIB and (18)F-FDG scans. CONCLUSION: The combined use of (11)C-PIB and (18)F-FDG PET provides relevant information for the clinical management of cognitive impairment. The detection of positive (11)C-PIB cortical retention in patients may be an indicator of the need for further clinical assessment and monitoring.

Aortic 18F-FDG PET/CT uptake pattern at 60 min (early) and 180 min (delayed) acquisition in a control population: a visual and semiquantitative comparative analysis.

18F-Fluoro-2-deoxy-D-glucose (F-FDG) PET/CT acquisition is generally performed 60 min after injection. The normal biodistribution pattern of F-FDG includes activity in the aortic territory due to blood pool activity, which could interfere in the diagnosis of aortic diseases by overlapping the wall uptake. The aim of the study was to evaluate the change over time of F-FDG uptake by the aortic wall and the activity in the lumen in a control population and to establish normal reference values. This prospective study included 15 control patients (mean age: 58.2 years). PET/CT was acquired 60 min (early scan) and 180 min (delayed scan) after an F-FDG injection at a dose of 7 MBq/kg. A visual and semiquantitative analysis of the F-FDG aortic wall uptake was carried out, and lumen activity and the aortic wall to lumen ratio [target-to-background ratio (TBR)] were determined. In the visual analysis all patients showed F-FDG activity at the aortic territory at 60 and 180 min. The pattern of uptake at 60 min was diffuse in all 15 patients (100%), without delineation of the aortic wall uptake; however, at 180 min the uptake pattern of the aortic wall changed to lineal in 14 patients (93.3%). The aortic wall maximum standardized uptake value decreased from 2.07±0.34 to 1.7±0.46 during the delayed acquisition (P=0.0279) and the lumen maximum standardized uptake value decreased highly significantly (1.99±0.35 vs. 1.36±0.32, P=0.0001). Therefore, TBR also increased highly significantly from 1.04±0.06 to 1.25±0.16 (P<0.0001). The high decrease in blood pool activity from 60 to 180 min provides a better delineation of the aortic wall uptake, which corresponds to the normal pattern at that time. The TBR increased significantly at 180 min, and 1.25±0.16 is suggested as the threshold for diagnostic purposes, especially for the diagnosis of vasculitis.

Diagnosis of recurrence and assessment of post-recurrence survival in patients with extracranial non-small cell lung cancer evaluated by 18F-FDG PET/CT.

UNLABELLED: The accurate diagnosis of recurrence of non small cell lung cancer (NSCLC) is crucial for the appropriate management of patients with suspicion of recurrence (SOR). We evaluated prospectively in the clinical setting the contribution of FDG PET/CT in patients with SOR of NSCLC in terms of sensitivity, specificity, impact on therapy and on survival. METHODS: Of the 55 patients included in the study, recurrence was confirmed in 37 but, follow up data for survival evaluation was available in 34. There were 59 SOR in the 55 patients and in 41 recurrence was confirmed. 53 of the 59 suspicions, had a contrast enhanced CT. All patients had a FDG PET/CT scan after iv injection of 8 MBq/kg of F18-FDG. RESULTS: Of the 59 SOR, FDG PET/CT was positive in all 41 in which recurrence was confirmed (100% sensitivity) and, it was negative in 15 of the 18 in which it was ruled out (specificity 83%). In 27 SOR with inconclusive CT, FDG PET/CT showed 100% sensitivity (18/18) and 78% specificity (7/9). FDG PET/CT had an impact on treatment in 42 of the 59 SOR. In all 34 patients, FDG PET/CT diagnosed recurrence and overall survival at 20 months and 5 years was 44% and 11%, respectively. When the extent of recurrence assessed by FDG PET/CT was considered, survival at 20 months and at 5 years of patients with loco-regional recurrence was 77% and 28% and in patients with distant recurrence 14% and 0% (p < 0.001). CONCLUSION: Despite the small number of patients, our study demonstrates that FDG PET/CT is highly accurate for the detection of NSCLC recurrence. Therefore it has a great impact on the therapy regimen and on survival depending on the extent of the recurrent disease, survival being better for patients with local recurrence. By differentiating local from distant recurrence, it allows the selection of patients who, could potentially benefit from new therapies. The results also suggest that there are grounds to include FDG PET/CT in the guidelines for surveillance for NSCLC.