Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD.</p> <p>We have therefore set out to conduct a prospective study testing the diagnostic accuracy of TCD in patients with a parkinsonism of unclear origin.</p> <p>Methods/Design</p> <p>We will enrol 250 consecutive patients, who are referred to neurology outpatient clinics of two teaching hospitals, for analysis of clinically unclear parkinsonism. Patients, whose parkinsonism is clearly diagnosable at the first visit, will be excluded from the study. All patients will undergo a TCD of the substantia nigra. As a surrogate gold standard we will use the consensus clinical diagnosis reached by two independent, blinded, movement disorder specialist neurologists after 2 years follow-up. At the time of TCD, patients will also undergo a SPECT scan of the brain.</p> <p>Discussion</p> <p>As this prospective trial enrols only patients with an early-stage parkinsonism, it will yield data on the diagnostic accuracy of TCD that is relevant to daily clinical practice: The neurologist needs a diagnostic tool that provides additional information in patients with a clinically indefinable parkinsonian syndrome. The above described observational longitudinal study was designed to explicitly study this aspect in the diagnostic process.</p> <p>Trial registration</p> <p><b>(ITRSCC) NCT00368199</b></p

Metaiodobenzylguanidine scintigraphy in pulmonary and cardiac disease

Purpose of review Nuclear medicine techniques have the capacity to investigate neuronal dysfunction at the synapse level. For instance, metaiodobenzylguanidine (MIBG) shows a similar uptake, storage and release as norepinephrine. Intravenously injected radiolabeled MIBG is able to reflect neuronal damage induced by inflammation and tumors. The purpose of this review is to evaluate the results and the limitation of these neuronal imaging techniques in patients with pulmonary and cardiac diseases and to give an opinion about the clinical value of these new diagnostic tools. Recent findings MIBG neuronal images of the lungs and heart can show heterogeneous distribution patterns with either diminished or increased MIBG uptake and/or washout. These changes reflect changes in endothelial integrity, neuronal innervations and clearance of norepinephrine. Interest in the role of neurotransmitter involvement and the relation between endothelial cell integrity and vascularization is growing and of utmost importance to understand the effect on pathophysiology of diseases. Summary At this moment, there is no added clinical value to routinely use MIBG scanning of the lungs and the heart. This is partly due to the many unresolved questions such as what actually happens and which factors influence MIBG uptake and washout under normal physiological circumstances. But the technique, if standardized and when dynamic time acquisition is performed with the latest equipment, such as PET and single photon emission computed tomography-computed tomography (SPECT-CT), has a tremendous potential. It can unravel upto now unknown relationships between innervation, vascularization and endothelial integrity. Other diagnostic tools such as MRI and CT do not have this capacity, so the future looks bright for these new neuronal imaging techniques

Retention of 99mTc-DMSA(III) and 99mTc-nanocolloid in different syringes affects imaging quality

(99m)Tc-dimercaptosuccinic acid [DMSA(III)] and colloidal human serum albumin ((99m)Tc-nanocolloid) are widely used radiopharmaceuticals. Recently, in our institution we encountered image quality problems in DMSA scans after changing the brand of syringes we were using, which triggered us to look into the adsorption properties of syringes from different brands for (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid. We also describe a clinical case in which adsorption of (99m)Tc-DMSA(III) caused inferior imaging quality. DMSA and nanocolloid were labeled with (99m)Tc following manufacturer guidelines. After synthesis, syringes with (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid were stored for 15, 30, 60, and 120 min. We evaluated Luer Lock syringes manufactured by different brands such as Artsana, Henke-Sass-Wolf, B. Braun Medical N.V., CODAN Medizinische Gerate GmbH &amp; Co KG, Becton Dickinson and Company, and Terumo Europe. Adsorption of (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid was acceptably low for all syringes (&lt;13%), except for two brands with (99m)Tc-DMSA(III) adsorption rates of 36 and 30%, respectively, and for one brand with a (99m)Tc-nanocolloid adsorption rate of 27%. Adsorption of (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid reaches critical levels in syringes produced by two brands, potentially causing poor image quality--for example, in DMSA scans using pediatric radiopharmaceutical doses. It is advised to check the compatibility of any radiopharmaceutical with syringes as an integral part of the quality assurance program

F-18 FDG PET/CT scanning in Charcot disease: a brief report

PURPOSE: because of the increasing prevalence of diabetes, complications of diabetes will also become more prevalent. The pathophysiology of Charcot neuro-osteoarthropathy (Charcot disease) as a complication of diabetes is still enigmatic. As a consequence, the optimal diagnostic, follow-up, and therapeutic strategies are unclear. To obtain more insight into the relation between bony abnormalities and the (concurrent) inflammatory response in acute Charcot disease, thereby creating more insight into the pathophysiology of this disease, we performed F-18 FDG PET/CT scanning. RESEARCH DESIGN AND METHODS: We performed F-18 FDG PET/CT and Tc-99m bone scintigraphy in 10 patients with Charcot disease. Bony abnormalities on CT-scan and areas of increased uptake on F-18 FDG PET and Tc-99m bone scintigraphy were assessed independently. Subsequently, fused PET/CT images were evaluated for number and location of PET lesions. RESULTS: nine patients had increased uptake of F-18 FDG, indicating inflammation, in 25 areas of soft tissue and/or bone without concurrent bony abnormalities on CT. CONCLUSIONS: presented F-18 FDG PET/CT data may indicate an inflammatory origin of Charcot disease, with secondary bone resorption, possibly due to decreased inhibitory neurogenic inflammatory responses as a result of small fiber neuropathy. If these findings can be confirmed in future studies, F-18 FDG PET/CT scanning may be added to the diagnostic arsenal in Charcot disease, and anti-inflammatory drugs may be added to the therapeutic arsenal

Delta-9-Tetrahydrocannabinol-Induced Dopamine Release as a Function of Psychosis Risk: F-18-Fallypride Positron Emission Tomography Study

Cannabis use is associated with psychosis, particularly in those with expression of, or vulnerability for, psychotic illness. The biological underpinnings of these differential associations, however, remain largely unknown. We used Positron Emission Tomography and (18)F-fallypride to test the hypothesis that genetic risk for psychosis is expressed by differential induction of dopamine release by Δ(9)-THC (delta-9-tetrahydrocannabinol, the main psychoactive ingredient of cannabis). In a single dynamic PET scanning session, striatal dopamine release after pulmonary administration of Δ(9)-THC was measured in 9 healthy cannabis users (average risk psychotic disorder), 8 patients with psychotic disorder (high risk psychotic disorder) and 7 un-related first-degree relatives (intermediate risk psychotic disorder). PET data were analyzed applying the linear extension of the simplified reference region model (LSRRM), which accounts for time-dependent changes in (18)F-fallypride displacement. Voxel-based statistical maps, representing specific D2/3 binding changes, were computed to localize areas with increased ligand displacement after Δ(9)-THC administration, reflecting dopamine release. While Δ(9)-THC was not associated with dopamine release in the control group, significant ligand displacement induced by Δ(9)-THC in striatal subregions, indicative of dopamine release, was detected in both patients and relatives. This was most pronounced in caudate nucleus. This is the first study to demonstrate differential sensitivity to Δ(9)-THC in terms of increased endogenous dopamine release in individuals at risk for psychosis.status: publishe

Radionuclide tumor necrosis factor-alpha activity in herniated lumbar disc correlates with severe leg pain

Background: Lumbar disc herniation is often associated with an inflammatory process. In this context, inflammation has been considered a key factor in the modulation of pain. Here, we present a case of inflammatory activity directly documented in a patient with a lumbar disc herniation. Case Description: A 49-year-old male presented with progressive low back pain and left-sided S1 radiculopathy, without a focal neurological deficit. The lumbar MR revealed a prominent herniated disc at the L5-S1 level, with compression of the left S1 root. The patient underwent a L5-S1 discectomy using a standard interlaminar approach. Although initially he was pain free, he required three additional operations to address recurrent pain complaints. As research indicates that local inflammation contributes to neuropathic pain, we had the patient undergoes single-photon emission computed tomography (SPECT) imaging using technetium-99m-labeled-infliximab (an anti-tumor necrosis factor [TNF]-alpha monoclonal antibody) before a proposed fourth operation. The SPECT study documented a strong signal at the site of the herniated disc, thus confirming the diagnosis of a pro-inflammatory process involving the S1 nerve root. Nine months after the fourth operation, the patient was pain free. Of interest, the second SPECT study in the now asymptomatic patient demonstrated no detectable/ residual signal at the operative/disc site. Conclusion: Absence of a SPECT TNF-alpha signal in a pain-free patient following a lumbar discectomy correlates with the reduction/resolution of the local preoperative inflammatory response