ObjectiveImpulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [11C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [123I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density.MethodsThe [123I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests.ResultsThose with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls.ConclusionsOur findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.
We describe the use of Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) in the investigation and diagnosis of Charcot neuroarthropathy (CN) in patients with a hot swollen foot but normal radiographs and clinical suspicion of CN, usually termed Stage 0. This was a retrospective cohort review of 46 diabetes patients who underwent 3 phase bone scintigraphy with “High Resolution” SPECT/CT. The imaging demonstrated that Stage 0 Charcot foot has a distinct bone pathology, which can be classified into three groups: (1) fractures on Computed Tomography (CT) with accompanying focal uptake of tracer on SPECT, (2) bony abnormalities apart from fracture on CT with focal uptake of tracer on SPECT, and (3) normal CT but focal bony uptake of tracer on SPECT. The CT component of SPECT/CT detected bony fractures in 59% of patients. Early treatment with below knee cast and follow-up for 24 months showed only 4 patients who developed Stage 1 Eichenholtz Charcot foot. Our findings support the use of 3 phase bone scintigraphy with SPECT/CT in the characterization and early diagnosis of CN. Stage 0 Charcot foot has a distinct bone pathology which requires urgent treatment to prevent progression to Stage 1 Eichenholtz Charcot foot. If SPECT/CT is unavailable, CT alone will detect bone fracture in 59% patients.
Background 177 Lu-DOTATATE peptide receptor radionuclide therapy is administered to patients on an inpatient and outpatient basis for the treatment of well-differentiated, metastatic neuroendocrine tumours. Following administration, these patients present an external radiation hazard due to the gamma emissions of lutetium-177. The purpose of this study was to determine precautions to be observed by 177 Lu-DOTATATE patients to restrict the dose received by patients’ family members to less than 5 mSv in 5 years and members of the public to less than 1 mSv per year in line with the current UK legislation. Retrospective data from therapeutic administrations of 177 Lu-DOTATATE (Mallinckrodt Pharmaceuticals) and Lutathera® (Advanced Accelerator Applications) were analysed to measure activity retention at discharge. Patient dose rate measurements were assumed to follow the same activity decay curve as that derived from a least squares fit of geometric mean counts in planar whole-body scans performed at four time points post-administration. Combining this with social contact times, the cumulative dose received through contact with the patient was estimated and an iterative process used to determine the length of contact restrictions to ensure the relevant dose constraints are not exceeded. Results On average, 36% of the administered activity was retained at the time of discharge for inpatients receiving 177 Lu-DOTATATE (Mallinckrodt). Retentions of 24% and 38% were measured for Lutathera® inpatients and outpatients respectively. Inpatients should restrict day contact and sleep separately from their partner for 15 days and remain off work for 5 days post-therapy. Contact with children for whom the patient is the main carer should be restricted for 16, 13 and 9 days for children below 2, 2–5 and 5–11 years respectively. One additional day is added to outpatient restriction periods, except for children aged 2–5 years which remains 13 days. No private transport restrictions are required. Patients should limit travel by public transport to 1 h on the day of discharge. Conclusion Restrictions are necessary to limit radiation dose to members of patients’ household and the public. Proposed precautions for inpatient and outpatient 177 Lu-DOTATATE therapy protocols restrict the dose received to less than the limit imposed by the UK legislation.
Background: Ethnic phenotypic differences in Parkinson’s disease (PD) are important to understand the heterogeneity of PD and develop biomarkers and clinical trials. Objective: To investigate (i) whether there are non-motor symptoms (NMS)-and comorbidity-based phenotypic differences between Black, Asian and Minority Ethnic (BAME) and White PD patients and (ii) whether clinically available biomarkers may help differentiate and explain the diversity. Methods: This is a multicentre (four sites, London), real-life, cross-sectional study including PD patients of BAME or White ethnicity. The primary outcome was a detailed NMS assessment, additional measurements included disease and motor stage, comorbidity, sociodemographic parameters and brain MRI imaging. Results: 271 PD patients (54 Asian, 71 Black, and 146 White) were included balanced for age, gender, and disease severity (HY). Black patients had a shorter disease duration compared to White and Asian populations. The SCOPA-Motor activities of daily living scores as well as the NMSS scores were significantly higher in both Black (total score and domain “miscellaneous”) and Asian (total score and domains “sleep/fatigue”, mood/apathy” and perception/hallucinations) than White individuals. Both BAME populations had higher prevalence of arterial hypertension, and the Black population had a higher prevalence of diabetes mellitus. Brain MRI revealed a greater severity of white matter changes in Black compared to the White and Asian cohorts. Conclusion: These findings suggest differences in phenotype of PD in BAME populations with greater burden of NMS and motor disability and a higher rate of cardiovascular comorbidities.
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