Serotonergic pathology and disease burden in the premotor and motor phase of A53T α-synuclein parkinsonism: a cross-sectional study

Publication date: Available online 19 June 2019Source: The Lancet NeurologyAuthor(s): Heather Wilson, George Dervenoulas, Gennaro Pagano, Christos Koros, Tayyabah Yousaf, Marina Picillo, Sotirios Polychronis, Athina Simitsi, Beniamino Giordano, Zachary Chappell, Benjamin Corcoran, Maria Stamelou, Roger N Gunn, Maria Teresa Pellecchia, Eugenii A Rabiner, Paolo Barone, Leonidas Stefanis, Marios PolitisSummaryBackgroundBecause of the highly penetrant gene mutation and clinical features consistent with idiopathic Parkinson's disease, carriers of the autosomal dominant Ala53Thr (A53T; 209G→A) point mutation in the α-synuclein (SNCA) gene are an ideal population to study the premotor phase and evolution of Parkinson's pathology. Given the known neurochemical changes in the serotonergic system and their association with symptoms of Parkinson's disease, we hypothesised that carriers of the A53T SNCA mutation might show abnormalities in the serotonergic neurotransmitter system before the diagnosis of Parkinson's disease, and that this pathology might be associated with measures of Parkinson's burden.MethodsIn this cross-sectional study, we recruited carriers of the A53T SNCA mutation from specialist Movement Disorders clinics in Athens, Greece, and Salerno, Italy, and a cohort of healthy controls with no personal or family history of neurological or psychiatric disorders from London, UK (recruited via public advertisement) who were age matched to the A53T SNCA carriers. We ...
Source: The Lancet Neurology - Category: Neurology Source Type: research

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ConclusionsVisual assessment of [123I]FP-CIT SPECT imaging by community nuclear medicine physicians in patients with early PD is reliable. Neurologists who request DAT SPECT scans are not always aware that the high accuracy is limited only to the differentiation between neurodegenerative and non-neurodegenerative parkinsonism. A significant portion of neurologists who request DAT SPECT scans is not always aware that the high accuracy is limited to the differentiation between neurodegenerative and non-neurodegenerative parkinsonism as DAT SPECT cannot reliably distinguish the various Parkinsonian syndromes.
Source: EJNMMI Research - Category: Radiology Source Type: research
AbstractPurposePrevious studies in patients with Parkinson ’s disease (PD) and impulse control disorders (ICDs) have produced heterogeneous results regarding striatal dopamine transporter (DaT) binding and activity in the mesocorticolimbic network. Our aim here was to study the relationship between striatal DaT availability and cortical metabolism, as wel l as motor, behavioural and cognitive features of PD patients with ICD.MethodsIn a group of PD patients with ICD (PD-ICD,n = 16) and 16 matched PD patients without ICD (PD-noICD,n = 16), DaT single-photon emission computed tomography (SPE...
Source: European Journal of Nuclear Medicine and Molecular Imaging - Category: Nuclear Medicine Source Type: research
ConclusionSemiquantitative123I-FP-CIT SPECT striatal evaluation combined with SVM represents a promising approach to disentangle PD from non-degenerative conditions and from atypical PS at the early stage.
Source: Journal of Neurology - Category: Neurology Source Type: research
AbstractPurpose of ReviewWhilst gait impairment is a main cause for disability in Parkinson ’s disease (PD), its neural control remains poorly understood. We performed a systematic review and meta-analysis of neuroimaging studies of surrogate features of gait in PD.FindingsAssessing the results from PET or SPECT scans after a period of actual walking as well as fMRI during mental imagery or virtual reality (VR) gait paradigms, we found a varying pattern of gait-related brain activity. Overall, a decrease in activation of the SMA during gait was found in PD compared to elderly controls. In addition, the meta-analysis ...
Source: Current Neurology and Neuroscience Reports - Category: Neuroscience Source Type: research
Conclusions: We proposed the new quantitative index "f-DTV" on DAT SPECT. It was strongly correlated with SBR and had a high diagnostic ability for differentiating PD from non-PD. F-DTV can evaluate both the volume and degree of active dopamine transporter at once, making it a useful marker in Parkinson syndrome.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Technologist Posters Source Type: research
1488Introduction: Dopamine transporter SPECT is an established method to investigate nigrostriatal integrity in case of clinically uncertain parkinsonism. The present study investigated whether a completely data-driven analysis of FPCIT SPECT is able to stratify patients according to mortality risk. This was tested in a clinical patient sample. Patients from our clinical registry were included if they had received FPCIT SPECT between 10/2008 and 06/2016 for diagnosis of parkinsonism and if their vital status (alive or date of death, if applicable) could be determined in 07/2017. Atlas-based regions of interest were used to...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Neurology & amp; Psychiatry Imaging Posters Source Type: research
Conclusions: One-third time TRODAT SPECT imaging performed on a cardiac- dedicated CZT SPECT scanner might be feasible to measure the SBR. However, major challenges come from improper positioning and image truncation related to patients’ head and shoulder sizes.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Technologist Posters Source Type: research
Conclusions: Striatal Tc-99m TRODAT-1 binding is significantly lower in patients with MSA than in those with PD. Among MSA group, the uptake is lower in MSA-P group than MSA-C group. The trend of asymmetric nigrostriatal damage was more obvious in PD than in MSA, and among MSA group, more asymmetry in MSA-P than in MSA-C patients, especially in caudate. This finding may assist clinicians for early differential diagnosis of patients with parkinsonism and provide a clue for the pathophysiology of PD and MSA. Table 1. Available Population CharacteristicsCharacteristicPDMSA-PMSA-CNo. of patients142014Sex (F/M)8/613/77/7Age at ...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Brain Imaging Reloaded I Source Type: research
Conclusion: Significant asymmetry with the contralateral side being affected more than the ipsilateral side was a hallmark in patients with lateralization of symptoms, i.e. in TD PD group. The binding ratio of the ipsilateral striatum may serve useful in following the progression of the disease and in prognosticating the clinical course, as it represents the level of remaining functional dopaminergic neuronal reserve in the striatum.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Brain Imaging Reloaded I Source Type: research
Conclusion Taken together, evidence from animal and human studies demonstrates that the brain detects levels of circulating nutrients and hormones and consequently organizes an outward response that contributes to the regulation of whole-body glucose homeostasis. However, there are major knowledge gaps about the exact nature of this response and its relative importance compared to peripheral processes. As we have seen, animal studies have provided an anatomical map of CNS glucose regulation and have identified important neurons and neural circuits involved. Additionally, the CNS sensing of key nutrients and hormones has b...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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