Validation of cardiac 123I-MIBG scintigraphy in patients with Parkinson’s disease who were diagnosed with dopamine PET

Purpose  

The aim of this study was to evaluate the diagnostic potential of cardiac ¹²³I-labelled metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy in idiopathic Parkinson’s disease (PD). The diagnosis was confirmed by positron emission tomography (PET) imaging with ¹¹C-labelled 2β-carbomethoxy-3β-(4-fluorophenyl)-tropane (¹¹C-CFT) and ¹¹C-raclopride (together designated as dopamine PET).     

The effect of levodopa therapy on dopamine transporter SPECT imaging with 123I-FP-CIT in patients with Parkinson’s disease

Purpose The aim of this study was to evaluate, by means of ¹²³I-FP-CIT SPECT, the effect of chronic treatment with levodopa on striatal dopamine transporter (DAT) in patients with Parkinsons disease.Methods Fifteen patients under stable levodopa/carbidopa monotherapy were imaged twice: at baseline on medication and after at least 20 days of treatment wash-out. DAT levels were assessed from SPECT imaging for the entire striatum, the right and left striatum, the right and left putamen and the right and left caudate, as a ratio of regional brain activities using the formula: (striatal region of interest–occipital)/occipital.Results During levodopa wash-out, despite a worsening in patients clinical disability (H&Y mean stage 2.53±0.58 versus 1.73±0.45 on therapy, p<0.001), striatal ¹²³I-FP-CIT levels were not significantly different from those at baseline in any of the brain regions examined.Conclusion The results of this study suggest that levodopa does not affect ¹²³I-FP-CIT brain imaging and confirm that it is not necessary to withdraw this medication to measure DAT levels with SPECT.     

Comparison of dopamine turnover, dopamine influx constant and activity ratio of striatum and occipital brain with 18F-dopa brain PET in normal controls and patients with Parkinson��s disease

Purpose

The aim of the study was to estimate normal ranges and test-retest measures for various parameters characterising dopamine metabolism from a prolonged ¹⁸F-dopa positron emission tomography (PET) measurement using a reference tissue model and compare their value for the detection of early Parkinson??s disease (PD).

Methods

Healthy volunteers (n?=?9) and patients (n?=?36) in an early stage of PD underwent an ¹⁸F-dopa PET measurement lasting 4?h. The influx rate constant k_occ and the effective distribution volume ratio (EDVR, its inverse is an indicator for dopamine turnover) were estimated by a graphical approach using dynamic data in the striatum and, as a reference region, the occipital cortex. Furthermore, ratios of activity concentrations between striatum and occipital brain taken for three time intervals completed the data analysis. All parameters were determined both in eight small volumes of interest placed in the striatum as well as averaged for caudate nucleus and putamen. For the control group, reproducibility was checked in a second study 3?months later and ranges for normal values were derived from mean?±?2 standard deviations. Receiver-operating characteristic (ROC) analyses were performed to assess the value of the parameters for diagnostic purposes.

Results

Patients with early-stage PD and healthy volunteers could be separated by the values of the putamen, not the caudate nucleus. The normal ranges of the putamen were 0.0151?C0.0216/min for the influx rate constant k_occ and 2.02?C3.00 for EDVR. For the various time intervals used the striato-occipital ratios yielded 2.24?C3.06, 2.43?C3.42 and 2.35?C3.21, respectively. Patients were characterised by significantly lower values (p?p?occ for the putamen were able to effectively differentiate between groups (sensitivity >97%, specificity 100%). In contrast, striato-occipital ratios showed a sensitivity of about only 85%.

Conclusion

For clinical applications, our data do not demonstrate any superiority of the EDVR determination compared to influx rate constant, while requiring long and tedious acquisition protocols. The normal range estimates do not represent absolute quantitative measures for dopamine metabolism but are specific for the chosen acquisition and processing procedures.     

[123I]β-CIT single-photon emission tomography in Parkinson's disease reveals a smaller decline in dopamine transporters with age than in controls

In vivo studies using single-photon emission tomography (SPET) and positron emission tomography have shown an age-related decline in the number of striatal dopamine transporters in healthy subjects. We examined ten healthy subjects and 33 de novo patients with Parkinson's disease (PD) using [¹²³I]2-carbomethoxy-3-(4-iodophenyl)tropane ([¹²³I]-CIT) SPET. A clear age-related loss of dopamine transporters was found in the healthy subjects. In the PD group, controlling for the contribution of disease severity, we found a small (compared with controls) but significant decrease with aging, though only in the ipsilateral regions. This aging effect was especially pronounced in younger patients. We conclude that the use of age-correct SPET data in PD, based on studies with healthy subjects, may lead to an underor an overestimation of the striatal binding measures.     

Differences in [99mTc]TRODAT-1 SPECT binding to dopamine transporters in patients with multiple system atrophy and Parkinson’s disease

Purpose Multiple system atrophy (MSA), a disorder causing autonomic dysfunction, parkinsonism, and cerebellar dysfunction, is difficult to differentiate from other movement disorders, particularly early in the course of disease. This study evaluated whether [^99mTc]TRODAT-1 binding to the dopamine transporter differentiates MSA from other movement disorders.Methods Single-photon emission computed tomographic brain scans were acquired in 25 MSA patients, 48 age-matched controls, and 130 PD patients, 3 h after the injection of 740 MBq (20 mCi) of [^99mTc]TRODAT-1. Regions of interest (ROIs) were placed manually on subregions of both basal ganglia and distribution volume ratios (DVRs) were calculated. Regional DVRs were compared between study groups in MSA patients. Students t tests were used to compare MSA patients with other study groups. Spearman correlations were used to compare DVRs with NP measures.Results Based upon various motor scores, MSA and PD patients had comparable motor impairment, and were significantly impaired compared with controls. Mean DVRs in the basal ganglia of MSA patients were significantly less than those of controls, but generally higher (p<0.05) than in PD patients. In particular, the MSA patients had significantly increased DVRs in the posterior putamen (mean 0.49±0.30) compared with PD patients (0.74±0.25).Conclusion Movement disorder patients could be differentiated from controls, but MSA and PD patients could not be easily differentiated from each other. As a group, MSA patients had significantly higher mean [^99mTc]TRODAT-1 binding, particularly in the posterior putamen, compared with PD patients and significantly lower binding compared with controls. This may reflect different pathophysiological processes of the two neurodegenerative diseases.     

123I-FP-CIT SPECT imaging of dopamine transporters in patients with recurrent sudden falls: are such falls a distinct entity?

Recurrent falls in older people are commonly associated with abnormalities that involve several parts of the central nervous system, especially with basal ganglion pathology. The aim of the present study was to evaluate the integrity of striatal dopamine transporters (DaTs) by use of (123)I-N-3-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ((123)I-FP-CIT) SPECT of striatal DaTs in patients with recurrent sudden falls. METHODS: Twenty-one patients without a definite neurologic diagnosis for recurrent sudden falls were enrolled in a cross-sectional study. SPECT with a DaT ligand was performed 180 min after injection of 185 MBq of (123)I-FP-CIT with a dual-head gamma-camera. RESULTS: DaT SPECT findings were normal in 15 of 21 patients (71%). Of those, 73% had abnormal MRI findings suggestive of atherosclerotic lesions. Eleven patients with normal DaT SPECT findings had mild parkinsonian symptoms. There was no correlation of the SPECT results with patient age, duration of occurrence of falls, or frequency of falls, and there was no significant difference in the relative distributions of SPECT findings between patients with and patients without parkinsonian symptoms or vascular risk factors. CONCLUSION: Recurrent sudden falls are, in most cases, not attributable to the degeneration of the nigrostriatal system.     

Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson’s disease

Purpose

Reduced presynaptic dopaminergic activity plays an important role in the development of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). In this study, we investigated whether dopaminergic function in the nigrostriatal system is associated with the timing of LID onset.

Methods

From among 412 drug-naive PD patients who underwent a dopamine transporter (DAT) PET scan during their baseline evaluation, we enrolled 65 patients who developed LID during a follow-up period of >2 years. Based on the time from PD onset, LID was classified as early, intermediate or late onset. We then compared DAT availability in the striatal subregions of the patients in the three groups.

Results

The demographic characteristics did not differ among the three patient groups except for earlier intervention of levodopa therapy in the early LID onset group (p = 0.001). After adjusting for age at PD onset, gender, timing of levodopa therapy from PD onset, and the severity of PD motor symptoms, DAT activity in the posterior putamen was found to be significantly lower in the early LID onset group than in the late LID onset group (p = 0.017). Multivariate linear regression analysis showed that low DAT activity in the posterior putamen was significantly associated with the early appearance of LID in the early LID onset group (β = 16.039, p = 0.033).

Conclusion

This study demonstrated that low DAT activity in the posterior putamen at baseline is a major risk factor for the early onset of LID in patients with PD, suggesting that the degree of presynaptic dopaminergic denervation plays an important role in determining the timing of LID onset.

     

Imaging of dopamine transporters and D<Subscript>2</Subscript> receptors in patients with Parkinson’s disease and multiple system atrophy

Purpose The aim of this study was to ascertain whether combined presynaptic and postsynaptic dopaminergic single-photon emission computed tomography (SPECT) scanning is useful for differentiation between patients with idiopathic Parkinsons disease (IPD), patients with multiple system atrophy of the striatonigral type (MSA) and healthy subjects.Methods SPECT measurements of the dopamine transporter (DAT) were done with ¹²³I--CIT, while for determination of the dopamine D₂-like receptors (D₂), ¹²³I-epidepride was used. Clinical evaluation and SPECT scans were carried out in 14 patients with IPD, eight patients with MSA and 11 healthy age-matched control subjects.Results Putaminal DAT binding was reduced to 32% of control values in IPD and to 19% of control values in MSA . Significantly higher striatal asymmetry in DAT binding was found in MSA than in controls, but IPD patients had significantly higher asymmetry than MSA patients. Striatal D₂ binding did not differ significantly between patients and healthy controls but the ratio between caudate DAT and D₂ binding was significantly higher in patients with IPD than in those with MSA, even when disease severity was taken into account.Conclusion Patients with reduced striatal ¹²³I--CIT binding and a side-to-side difference greater than 15% are likely to suffer from IPD. Patients with reduced striatal ¹²³I--CIT binding and a side-to-side difference of between 5% and 15% are more likely to have MSA. ¹²³I-epidepride SPECT measurements may add further diagnostic information, since the ratio between DAT and D₂ receptor binding is significantly higher in IPD than in MSA.     

Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson’s disease

Purpose

Parkinson’s disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor.

Methods

[¹²³I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates.

Results

Patients with PD had 28.1 – 65.0 % lower binding in all striatal regions compared to controls (p?p?Conclusion The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor.     

Changes in muscle activity in children with hemiplegic cerebral palsy while walking with and without ankle–foot orthoses

We compared the electromyographic (EMG) signals of lower extremity muscle groups in 10 children with hemiplegic cerebral palsy (CP) while walking barefoot and in a hinged ankle–foot orthosis (HAFO). All children had excessive plantarflexion and initial toe-contact on the affected side when walking barefoot, a typical gait pattern for hemiplegic patients. The patients walked with a physiological heel–toe gait pattern when wearing the HAFO. The peak activity of the tibialis anterior muscle was reduced by 36.1% at initial contact and loading response phase and by 57.3% just after toe-off when using a HAFO. The decrease in activity was thought to result from the change in gait pattern from a toe-gait to a heel–toe gait as well as the use of a HAFO. The HAFO also slightly decreased muscle activity in the proximal leg muscles mainly during swing phase, improved stride length, decreased cadence, improved walking speed, increased peak hip flexion, improved kinematics in loading response phase at the knee, and reduced the excessive ankle plantarflexion.     

Multislice CT with single–phase technique in patients with suspected pancreatic cancer

PURPOSE: The purpose of this study was to evaluate the role of multislice computed tomography (MSCT) with a single-phase technique in patients with suspected pancreatic cancer (PC). MATERIALS AND METHODS: Seventy-eight patients underwent MSCT with the following technical parameters: collimation: 4x1 mm; pitch 1; 120 kVp; 260 mAs. The pre-contrast scan was followed by a single acquisition phase in the caudocranial direction from the inferior hepatic margin to the diaphragm with a 60-s delay after IV administration of 150 ml of iodinated contrast material at a rate of 3 ml/s. Two radiologists assessed the single images independently. Receiver operating characteristics (ROC) curves were obtained for each of the two observers. RESULTS: The final diagnosis was pancreatic cancer in 46 cases and chronic pancreatitis in 32 cases. Areas under the curve (AZ) for diagnosis and evaluation of disease resectability were 0.97 and 0.93 for the first observer (p=ns), and 0.97 and 0.90 for the second observer (p=ns). The mean difference in tissue attenuation values between the cancer and normal pancreas was 72 +/- 3 Hounsfield units (HU). No statistically significant differences were observed in the degree of opacification between the peripancreatic arteries and veins. CONCLUSIONS: MSCT with a single-phase technique is an accurate and reproducible method for diagnosis and evaluation of disease resectability in patients with suspected PC, ensuring optimal tumour-to-pancreas contrast and maximal opacification of the main peripancreatic arterial and venous structures.     

Changes in Liver Congestion in Patients with Budd–Chiari Syndrome following Endovascular Interventions: Assessment with Transient Elastography

Purpose

Transient elastography (TE) is routinely used for noninvasive staging of hepatic fibrosis. The objective of the present study was to investigate the role of TE (FibroScan) in determining changes in liver congestion in patients with Budd–Chiari syndrome (BCS) treated by endovascular interventions and determine the effects of pretreatment Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) fibrosis score on posttreatment liver stiffness (LS).

Gait asymmetries in children with cerebral palsy: do they deteriorate with running?

In children with cerebral palsy (CP) analysis of gait asymmetry can provide insight into the control of walking and may help in guiding the clinician's treatment decisions. Running is more difficult that walking for the musculoskeletal system, however, in the literature it has been shown that gait deviations associated with CP maybe better tolerated during running. This leads us to the hypothesis that running might increase gait symmetry in patients with CP. Therefore the purpose of this study was to investigate the effect of running on asymmetries in spatio-temporal, kinematic and kinetic gait parameters for children with CP. Twenty-four children with diplegia and 25 with hemiplegia were examined using 3D gait analysis during running and walking. MANOVA on two factors: diagnosis (hemiplegic, diplegic) and movement (walking, running) was conducted on a total of 22 gait parameters. The MANOVA revealed a significant difference in symmetry between walking and running (p<0.001) and between patients groups (p=0.004). The detailed analysis of gait parameters demonstrated a significant decrease of symmetry in 13 of the 22 gait parameters investigated, only symmetry of step time was significantly increased. Therefore the hypothesis that gait symmetry improved with running in children with CP can be rejected. Based on the results of this study, asymmetries masked during walking might appear during running. Therefore, analysis of asymmetry of walking and running gives a more comprehensive assessment of the gait pathology for clinical decision making.     

PCI compared with medical therapy in elderly patients with chronic symptomatic coronary artery disease

PCI compared with medical therapy in elderly patients with chronic symptomatic coronary artery disease!050000$河北医科大学第二医院@刘晓堃 !050000$河北医科大学第二医院@傅向华 !050000$河北医科大学第二医院@马宁     

Vertebral augmentation with the SpineJack® in chronic vertebral compression fractures with major kyphosis

Objectives

Osteoporotic vertebral compression fractures (OVCFs) are an important health issue for which minimally invasive techniques are a feasible treatment. The SpineJack® (Vexim) is an intravertebral expandable system designed to improve the correction of the structural modifications caused by OVCFs. Its ability to stabilise and reduce OVCFs at the acute phase being already well established, we sought to evaluate the feasibility of vertebral augmentation with the SpineJack® in chronic kyphotic OVCFs.

Methods

All consecutive patients treated with the SpineJack® were prospectively included if they met the following criteria: (1) OVCF considered unstable (grade A3 according to Magerl’s classification). (2) Local kyphotic angle ≥ 20°. (3) OVCF older than 6 weeks. (4) Back pain with visual analogue scale (VAS) ≥ 4.

Results

Nineteen consecutive patients (16 women [84.2%] and 3 men [15.8%]; mean age 73.2 ± 8.2 years) were included. Treatment was performed after a mean delay of 5.8 months ± 2.9 (range 1.5–12). Median visual analogue scale significantly improved from 7 preoperatively (IQR 6–9) to 2 (IQR 1–5) at 6 months (p < 0.01). Significant kyphosis reduction (i.e. ≥ 30%) was obtained in 94.7% of cases. Secondary adjacent level fractures (SALFs) were noted in 21.1% of cases and were correlated with the importance of the kyphosis reduction.

Conclusions

Vertebral augmentation with the SpineJack® is feasible and seems able to correct major structural deformities in chronic OVCFs. SALFs were noted in a substantial amount of cases. Preventive adjacent vertebroplasty might be useful in patients with several risk factors for SALFs.

Key Points

? Vertebral augmentation with SpineJack® is effective to correct major structural deformities e.g. height loss and kyphosis. ? Successful reduction is reachable with SpineJack® in chronic (older than 6 weeks) OVCFs. ? Aggressive reduction of major kyphosis might promote SALFs and complementary adjacent vertebroplasties prevent their occurrence.

     

Usefulness of whole PTH assay in patients with renal osteodystrophy —Correlation with bone scintigraphy

OBJECTIVE: Intact parathyroid hormone (PTH) assay has recently been reported to be effective in evaluating both 1-84 PTH (whole PTH) and inactive 7-84 PTH. Inactive 7-84 PTH is considered to be increased in hemodialysis patients and to prevent the effects of 1-84 PTH, and intact PTH is considered to overestimate the PTH activity in these patients. As such, a whole PTH assay has recently been developed. The purpose of this study was to examine the usefulness of a whole PTH assay using the bone to soft tissue (B/ST) ratio on bone scintigraphy. METHOD: Twenty-five hemodialysis patients were included in our study. In all patients, bone scintigraphy and a blood test [whole PTH, intact PTH, alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P)] were performed. Regions of interest (ROIs) were drawn around the cranium, lumbar vertebrae, left femoral neck, and soft tissue of the medial left thigh to obtain the B/ST ratio. RESULTS: The B/ST ratio of the cranium and left femoral neck correlated with whole PTH and intact PTH. In particular, the B/ST ratio of the cranium correlated most significantly with the value of whole PTH. Whole PTH levels correlated with intact PTH levels (r = 0.891, p < 0.0001). CONCLUSION: Our data indicate that a whole PTH assay may be useful in evaluating PTH activity using the B/ST ratio. The B/ST ratio of the cranium may reflect the bone metabolism of hemodialysis patients.