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Background: Non-motor symptoms (NMSs) are clearly more prevalent in Parkinson's disease (PD) patients compared to healthy individuals. However, NMSs are also common in the elderly and other neurological conditions, and thus, it is not known whether NMSs could be used to differentiate PD from parkinsonism/tremor without dopamine deficiency. Methods: We prospectively evaluated NMSs immediately before brain dopamine transporter (DAT) [I-123]FP-CIT SPECT scanning in 193 patients with unclear parkinsonism/tremor. According to the clinical follow-up and imaging results, 84 patients had PD. NMSs and their correlations with striatal DAT binding were investigated in PD patients and in parkinsonism/tremor patients with normal dopamine function. Results: Total NMS burden, anxiety or depression did not differ between PD patients and patients with normal DAT binding. DAT-normal patients reported more perception-related (p = 0.045) and attention/memory-related NMSs than PD patients (p

Non-motor symptoms (NMSs) are clearly more prevalent in Parkinson's disease (PD) patients compared to healthy individuals. However, NMSs are also common in the elderly and other neurological conditions, and thus, it is not known whether NMSs could be used to differentiate PD from parkinsonism/tremor without dopamine deficiency.We prospectively evaluated NMSs immediately before brain dopamine transporter (DAT) [Total NMS burden, anxiety or depression did not differ between PD patients and patients with normal DAT binding. DAT-normal patients reported more perception-related (p = 0.045) and attention/memory-related NMSs than PD patients (p 0.001). Total NMS score did not correlate with striatal DAT binding in either group.In clinically uncertain cases, the total NMS burden cannot be used as a tool in distinguishing PD patients from patients with non-dopaminergic parkinsonism/tremor. Clinical screening of NMSs appears equally important in all patients with parkinsonism.

Introduction Total parkinsonian motor symptom severity correlates with presynaptic striatal dopamine function in patients with Parkinson’s disease. There is a lack of studies that have investigated the associations between parkinsonian motor signs and striatal dopaminergic deficiency in patients with parkinsonism of an unknown origin. Identification of specific motor signs associated with the highest likelihood of striatal dopamine deficiency could aid the differential diagnostics of parkinsonian and tremor syndromes. Methods In this cross-sectional clinical and imaging study, detailed motor examinations were performed for 221 patients with parkinsonism or tremor of an unknown origin immediately before dopamine transporter (DAT) [I-123]FP-CIT SPECT imaging. Region-of-interest and voxel-based methods were used to investigate striatal DAT deficiency in relation to individual motor signs. Results Upper extremity rigidity and facial expression were the only motor signs that differentiated patients with normal and abnormal striatal DAT function. The presence of any upper extremity rigidity showed the highest likelihood of DAT deficiency (OR 4.79, 95% CI 1.56–14.75, P = 0.006) followed by reduced facial expression (OR 2.14, 95% CI 1.14–4.00, P = 0.018). In patients with DAT deficits, reduced facial expression was associated with DAT deficiency specifically in the caudate nucleus, and increased upper extremity rigidity was associated with DAT loss in the dorsal putamen (FWE-corrected P

Significant weight-loss and diabetes remission have been reported after mini-gastric bypass (MGB). Concern has been raised regarding postoperative bile reflux (BR), but it has not been demonstrated in previous studies. We set out to find out if BR is evident in hepatobiliary scintigraphy after MGB. Nine consecutive patients, seven with type 2 diabetes, underwent MGB (15 cm gastric tube, 250-275 cm biliary limb) at our institution with a 12-month follow-up, with none lost to follow-up. Then, 10.7 months (8.6-13.0) after MGB, all patients underwent hepatobiliary scintigraphy and a reflux symptom questionnaire (GerdQ) was filled out. A gastroscopy with biopsies was done for all patients with a bile-reflux-positive scintigraphy. Mean age at operation was 56 years (41-65) and preoperative BMI 43.1 kg/m(2) (34.2-54.6). Mean %EWL was 83.9 (49.5-128.3) at 12 months. Four patients reached diabetes remission and two became insulin-independent. Hepatobiliary scintigraphy showed a transient BR into the gastric tube for five patients. Bile tracer was found in the gastric tube at 23-58 min after the tracer injection and highest activity was 8% (1-8%) at 58 min. Bile tracer was not found in the esophagus of any of the patients. One patient with a positive scintigraphy in the gastric tube required re-operation. Two patients with reflux symptoms had a negative scintigraphy. Our results indicate that transient bile reflux is common after MGB in the gastric tube, but not in the esophagus. The clinical relevance of bile reflux needs further studies.

The aim of this study was to test a multimodal event-related potential (ERP) paradigm in chronic solvent encephalopathy (CSE) to develop a sensitive method for the clinical diagnostics to CSE. The study comprised 11 CSE patients and 13 healthy controls. We used three tasks: an auditory odd-ball (AUD), a visual detection (VIS), and a recognition memory (MEM) task. The auditory and visual stimuli were presented in single- and dual-task conditions. The auditory P300 amplitude in single-task condition was smaller in the patient group than in the control group at the parietal (Pz) but not at the frontal midline electrode location. The auditory P300 response in the dual task condition AUD+VIS was unrecognizable in 8 of 11 patients and in 1 of 13 controls and in the AUD+MEM condition in 10 of 11 patients and in 4 of 13 controls. In the AUD+MEM condition, the auditory P300 amplitude at Pz was smaller in the patient group than in the control group. Reaction time for auditory stimuli in both dual conditions as well as for visual stimuli in AUD+VIS condition were in the patient group prolonged. The ERP results indicate that CSE patients present with slowed performance speed and difficulties in allocation of attention. Based on ERP results, the disturbance in brain activity in CSE seems to affect posterior aspects of the frontoparietal continuity. The multimodal paradigm seems promising as a tool for the clinical diagnostics of CSE.

Diffusion tensor (DT) imaging measures the random molecular diffusion of water in vivo and provides information on the microstructure of tissue. Ischemic brain damage leads to tissue disorganization and structural lost. We aimed to evaluate these changes in a rat model of focal stroke from the hyperacute to chronic phase by utilizing several DT indices. Adult male Wistar rats, subjected to temporary focal cerebral ischemia by suture occlusion of the middle cerebral artery for 90 min, and sham controls were serially imaged at 4.7 Tesla. DT scans were collected repeatedly during the hyperacute (2 and 3.5 h), acute (1, 2, and 3 days), subacute (4, 7, and 14 days), and chronic (4, 6, and 8 weeks) phases. We measured the evolution of DT indices (mean diffusivity (MD), axial diffusivity (λ ║ ), radial diffusivity (λ ┴ ), and fractional anisotropy (FA)) in the cortex, subcortex, and corpus callosum of the ischemic hemisphere. In the hyperacute phase, MD, λ ║ , and λ ┴ reduced with no change in FA. From the acute to subacute phase, MD, λ ║ , and λ ┴ normalized and thereafter increased, whereas FA decreased in all the tissues. In the chronic phase, MD, λ ║ , and λ ┴ continued to rise, whereas FA normalized in the corpus callosum and subcortex, but remained low in the cortex. We described structural tissue changes in ischemic rat brain longitudinally utilizing DT analysis. DT indices reveal different individual patterns reflecting different facades and phases of tissue injury. The use of several DT indices may improve accuracy in estimating the age of the brain injury and in detecting ongoing pathological events.

Transient ischemic attacks (TIAs) are brief neurological deficits ofcerebrovascular origin that are followed by complete clinical recovery. Although a plethora of animal models exist for ischemic stroke, a verified TIA model is lacking. We aimed to optimize such a model in mice, investigating the impact of varying durations (from 2.5 to 20 minutes) of intraluminal middle cerebral artery occlusion (MCAo). Three conditions were required to mimic clinical TIA reliably: 1) an objective demonstration of occlusion and reperfusion (assessed by laser Doppler flowmetry); 2) no permanent neurological deficit (assessed by sensorimotor neurological evaluation); and 3) no lesion at 24 hours after reperfusion (assessed by magnetic resonance imaging [MRI]). We observed high incidences of MRI lesions with MCAo durations of 15 minutes or longer. In contrast, no permanent neurological deficits or MRI lesions were observed in animals with MCAo below or equal to 10 minutes. Middle cerebral artery occlusion of 12.5 minutes rarely induced MRI lesions, but histopathologic evaluation using routine and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining revealed minute ischemic changes even after 2.5-minute MCAo. Abundance of necrotic and apoptotic changes gradually increased with the duration of ischemia. These results indicate that 10 minutes or shorter focal cerebral ischemia proves a suitable mouse TIA model; in addition, they indicate that MRI-negative microscopic ischemic damage may occur with even a few minutes of arterial occlusion.

The blood-brain barrier (BBB) is the principal regulator of blood-borne substance entry into the brain parenchyma. Therefore, BBB leakage, which leads to cerebral edema and influx of toxic substances, is common in pathological conditions such as cerebral ischemia, inflammation, trauma, and tumors. The leakage of BBB after ischemia-reperfusion injury has long been considered to be biphasic, although a considerable amount of discrepancies as for the timing of the second opening does exist among the studies. This led us to evaluate systematically and quantitatively the dynamics of BBB leakage in a rat model of 90-min ischemia-reperfusion, using gadolinium-enhanced (small molecule) magnetic resonance imaging and fluorescent dye Evans Blue (large molecule). BBB leakage was assessed at the following time points after reperfusion: 25 min, 2, 4, 6, 12, 18, 24, 36, 48, and 72 h, and 1, 2, 3, 4, and 5 weeks. We observed BBB leakage for both gadolinium and Evans Blue as early as 25 min after reperfusion. Thereafter, BBB remained open for up to 3 weeks for Evans Blue and up to 5 weeks for gadolinium. Our results show that BBB leakage after ischemia-reperfusion injury in the rat is continuous and long-lasting, without any closure up to several weeks. This is the first systematic and extensive study fully demonstrating BBB leakage dynamics following transient brain ischemia and the findings are of major clinical and experimental interest.

The Patlak plot analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows estimation of blood-brain barrier (BBB) leakage following temporary focal cerebral ischemia. Thus far, a systematic and quantitative in vivo evaluation of post-ischemic BBB leakage is lacking. Here, using DCE-MRI and the Patlak plot method, we quantitatively assessed BBB leakage in rats at the following time-points after reperfusion: 25 min, 2, 4, 6, 12, 18, 24, 36, 48, and 72 h, and 1, 2, 3, 4, and 5 weeks. Sham-operated animals served as controls. Data collected for each time-point were: the blood-to-brain transfer rate constant (K(i)) of the contrast agent gadolinium, distribution volume (V(p)), ischemic lesion volume, and apparent diffusion coefficient (ADC) values. Compared to controls, K(i), measured at all time-points, except for 5 weeks, appeared significantly different (p

Surgery or radiation therapy of metastatic cancer often damages lymph nodes, leading to secondary lymphedema. Here we show, using a newly established mouse model, that collecting lymphatic vessels can be regenerated and fused to lymph node transplants after lymph node removal. Treatment of lymph node–excised mice with adenovirally delivered vascular endothelial growth factor-C (VEGF-C) or VEGF-D induced robust growth of the lymphatic capillaries, which gradually underwent intrinsic remodeling, differentiation and maturation into functional collecting lymphatic vessels, including the formation of uniform endothelial cell-cell junctions and intraluminal valves. The vessels also reacquired pericyte contacts, which downregulated lymphatic capillary markers during vessel maturation. Growth factor therapy improved the outcome of lymph node transplantation, including functional reconstitution of the immunological barrier against tumor metastasis. These results show that growth factor–induced maturation of lymphatic vessels is possible in adult mice and provide a basis for future therapy of lymphedema.

Background Iodine-123-β-CIT, a single-photon emission computed tomography (SPECT) ligand for dopamine transporters (DATs), has been used for in vivo studies in humans, monkeys, and rats but has not yet been used extensively in mice. To validate the imaging and analysis methods for preclinical DAT imaging, wild-type healthy mice were scanned using 123I-β-CIT. Methods The pharmacokinetics and reliability of 123I-β-CIT in mice (n = 8) were studied with a multipinhole SPECT/CT camera after intravenous injection of 123I-β-CIT (38 ± 3 MBq). Kinetic imaging of three mice was continued for 7 h postinjection to obtain the time-activity curves in the striatum and cerebellum volumes. Five mice had repeated measures 4 h post-123I-β-CIT injection to provide an indication of test-retest reliability. The same five mice served as a basis for a healthy mean SPECT template. Results Specific binding of 123I-β-CIT within the mouse striatum could be clearly visualized with SPECT. The kinetics of 123I-β-CIT was similar to that in previously published autoradiography studies. Binding potential mean values of the test-retest studies were 6.6 ± 15.7% and 6.6 ± 4.6%, respectively, and the variability was 9%. The SPECT template was aggregated from the first and second imaging of the test-retest animals. No significant difference between the templates (P > 0.05) was found. From the test template, a striatal volume of 22.3 mm3 was defined. Conclusions This study demonstrates that high-resolution SPECT/CT is capable of accurate, repeatable, and semiquantitative measurement of 123I-β-CIT DAT binding in the mouse brain. This methodology will enable further studies on DAT density and neuroprotective properties of drugs in mice.