Iron-Deficiency Anemia as a Rare Cause of Cerebral Venous Thrombosis and Pulmonary Embolism

Cerebral venous thrombosis (CVT) is a relatively rare cause of stroke and has a wide spectrum of unspecific symptoms, which may delay diagnosis. There are many etiologies, including hematological disorders, trauma, infection, and dehydration. Iron-deficiency anemia (IDA) has been reported as an extremely rare cause of CVT, especially in adults

Scan without evidence of dopaminergic deficit: A 10-year retrospective study

123I-ioflupane SPECT is a powerful method to assess nigrostriatal dopamine system integrity. Several independent studies have shown that 1–15% of patients with suspected degenerative parkinsonism, mainly PD, have scans without evidence of dopaminergic deficit (SWEDD). It has been proposed that most SWEDD patients either present with a non-degenerative condition mimicking PD, such as atypical tremor or dystonia, or demonstrate an abnormal scan when repeated later. We here hypothesized that scan interpretation methods may also play a crucial yet underestimated role in this issue.Methods We previously established age-dependent reference values of striatal uptake by analyzing scans from a cohort of patients with non-degenerative conditions. We then studied a large population with well-established degenerative parkinsonism (N = 410, 80% with PD), using identical imaging protocol, to evaluate the prevalence of patients with normal scans based on routine visual assessment. Each scan was eventually reassessed using the same automated method as for controls and a detailed 3D analysis.Results Ten potential SWEDD cases (2.4%) were identified. However, both reassessment methods independently showed that these scans were all outside reference limits and/or visually abnormal when reexamined carefully, except for one case (0.2%) with corticobasal syndrome.Conclusion SPECT misinterpretation emerges as an important contributor to the SWEDD population, suggesting that suspected SWEDD cases should prompt not only a serious diagnosis challenge but, equally important, a detailed scan reassessment. True SWEDD cases seem extremely rare in degenerative parkinsonism. We propose that the very concept of SWEDD is more confusing than helpful and should be definitely abandoned

Feeling of presence in dementia with Lewy bodies is related to reduced left frontoparietal metabolism.

Funder: University of CambridgeFeeling of presence (FOP) refers to the vivid sensation of a person's presence near oneself and is common in Dementia with Lewy Bodies (DLB). Based on previous observations on epileptic subjects, we hypothesized that DLB subjects with FOP would harbour 18F-fluorodeoxyglucose PET hypometabolism in left parietal areas. 25 subjects (mean age 71.9 ± 6.7, disease duration at scan 1.7 ± 1.5 years) were included in the study, of whom nine (36%) experienced FOP. No significant between-group difference was observed regarding dopamine transporters striatal uptake (p = 0.64), daily dopaminergic treatment dosage (p = 0.88) and visual hallucinations (p = 0.83). Statistical parametric mapping showed that subjects with FOP had a significantly reduced glucose metabolism in several left frontoparietal areas (p < 0.001), including superior parietal lobule and precuneus. Interregional correlation analysis of these areas showed specific connectivity with right insula and putamen in the FOP subgroup and right orbitofrontal and superior frontal in subjects without FOP. This provides further evidence about the role of a left frontoparietal network and suggest a possible contribution of impaired orbitofrontal reality filtering associated with FOP

The architecture of the Rag GTPase signaling network

The evolutionarily conserved target of rapamycin complex 1 (TORC1) couples an array of intra- and extracellular stimuli to cell growth, proliferation and metabolism, and its deregulation is associated with various human pathologies such as immunodeficiency, epilepsy, and cancer. Among the diverse stimuli impinging on TORC1, amino acids represent essential input signals, but how they control TORC1 has long remained a mystery. The recent discovery of the Rag GTPases, which assemble as heterodimeric complexes on vacuolar/lysosomal membranes, as central elements of an amino acid signaling network upstream of TORC1 in yeast, flies, and mammalian cells represented a breakthrough in this field. Here, we review the architecture of the Rag GTPase signaling network with a special focus on structural aspects of the Rag GTPases and their regulators in yeast and highlight both the evolutionary conservation and divergence of the mechanisms that control Rag GTPases

Distinct spatiotemporal patterns for disease duration and stage in Parkinson’s disease

Purpose: To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson’s disease (PD).Methods: This retrospective study included 970 consecutive patients undergoing ¹²³I-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4 ± 11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7 ± 8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other.Results: Increasing disease stage was associated with an exponential decrease in ¹²³I-ioflupane uptake (R ²  = 0.1501) particularly in the head of the ipsilateral caudate nucleus (p p R ²  = 0.1532) particularly in the contralateral anterior putamen (p < 0.0001).Conclusion: We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 ¹²³I-ioflupane SPECT scans can be used for clinical and research applications

Establishing on-site reference values for 123I-FP-CIT SPECT (DaTSCAN®) using a cohort of individuals with non-degenerative conditions

To overcome the issue of reference values for DaTSCAN® requiring healthy controls, we propose an original approach using scans from individuals with non- degenerative conditions performed at one single center following the same acquisition protocol. Procedures: From a cohort of 970 consecutive patients, we identified 182 patients with a clinical diagnosis of non-degenerative parkinsonism or tremor and a visually normal DATSCAN®. Caudate nucleus (C), putamen (P), and striatum (S) uptake values, C/P ratios, and asymmetry indexes (AI) were calculated using semi-quantitative methods. Outcomes were assessed according to age and gender, and reference limits were established using the percentile approach. Results: A significant negative linear effect of age was found upon striatal nuclei uptake of 0.21–0.22 per decade (6.8 %/decade for striatum), whereas a potential gender influence proved unclear. Inferior reference limits were established at the 5th percentile. C/P ratios and AIs were not influenced by age or gender, and superior reference limits were set at the 95th percentile. Conclusions: We here propose a convenient approach to calculate site-specific reference limits for DaTSCAN® outcomes not requiring scanning healthy controls. The method appears to yield robust values that range within nearly identical limits as those obtained in healthy subjects

Neurological complications of sickle cell disease in Africa: protocol for a systematic review

INTRODUCTION: Sickle cell disease (SCD) is highly prevalent in Africa. Considered as a public health problem, it is associated with high morbidity and mortality. Neurological complications of SCD can cause significant disability with important socioeconomic and psychological impact on the patients and their families, and can even lead to death if not properly managed. There are important knowledge gaps regarding the burden of neurological complications of SCD in African populations. We propose to conduct the first systematic review to summarise the epidemiological data available on neurological complications of SCD in Africa. METHODS AND ANALYSIS: We will search PubMed, MEDLINE, EMBASE and the African Index Medicus from 1 January 1950 to 31 May 2016 for studies of neurological complications of SCD in Africa. After study selection, full-text paper acquisition, data extraction and synthesis, we will assess all studies for quality, risk of bias and heterogeneity. Appropriate methods of meta-analysis will be used to pool prevalence estimates from studies with similar features, globally and in major subgroups. This protocol complies with the 2015 Preferred Reporting Items for Systematic reviews and Meta-Analysis protocols (PRISMA-P) guidelines. ETHICS AND DISSEMINATION: The proposed study will use published data. Therefore, there is no requirement for ethical approval. This review is expected to provide relevant data to help quantify the burden of neurological complications of SCD in African populations, inform policymakers and identify further research topics. The final report of the systematic review will be published in a peer-reviewed journal and presented at conferences. REVIEW REGISTRATION NUMBER: CRD42016039574

11 C-PK11195 PET imaging and white matter changes in Parkinson's disease dementia.

There is evidence of increased microglial activation in Parkinson's disease (PD) as shown by in vivo PET ligand such as 11 C-PK11195. In addition, diffusion tensor imaging (DTI) imaging reveals widespread changes in PD, especially when the associated dementia develops. In the present case series, we studied five subjects with Parkinson's disease dementia (PDD). Our findings suggest that while DTI metrics mirror cognitive severity, higher 11 C-PK11195 binding seems to be associated with a relative preservation of both white matter tracts and cognition. Longitudinal studies are warranted to tackle the complex relationship between microglial activation and structural abnormalities in neurodegenerative conditions.We are grateful to our volunteers for their participation in the study. We thank the radiographers at Wolfson Brain Imaging Centre and the PET/CT unit, Addenbrooke's Hospital for their technical expertise and support in data acquisition. We thank Alzheimer Research UK, the National Institute for Health Research Cambridge Biomedical Research Centre (NIHR, RG64473) and the Wellcome Trust (JBR: 103838) for funding and support

Extrastriatal 123I-FP-CIT SPECT impairment in Parkinson's disease - the PPMI cohort.

BACKGROUND: Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD). We undertook a case-controlled analysis of 123I-FP-CIT SPECT images to measure extrastriatal serotonergic transporters (SERT) in PD using the Parkinson's Progression Markers Initiative (PPMI) cohort. METHODS: We included all PD (n = 154) and Control subjects (n = 62) with available 123I-FP-CIT SPECT imaging and high-resolution T1-weighted MRI for coregistration (PD: mean age 61.6 years, 62% male, disease duration 26 months, MDS-UPDRS III score 22). 123I-FP-CIT SPECT images were processed with PETPVE12 using an exploratory voxel-wise analysis including partial-volume effect correction. Linear regressions were performed in the PD group to assess correlations between region of interest 123I-FP-CIT uptake and clinical motor and non-motor impairment. RESULTS: Compared to Controls, PD exhibited an uptake reduction in bilateral caudate nucleus, putamen, insula, amygdala and right pallidum (family-wise error (FWE)-corrected p  0.45) or excessive daytime sleepiness (all p > 0.29). CONCLUSIONS: In addition to the well-established striatal deficit, this study provides evidence of a major extrastriatal 123I-FP-CIT impairment, and therefore of an altered serotonergic transmission in early PD

Peak Width of Skeletonized Mean Diffusivity as a Marker of Diffuse Cerebrovascular Damage.

The peak width of skeletonized mean diffusivity (PSMD) has been proposed as a fully automated imaging marker of relevance to cerebral small vessel disease (SVD). We assessed PSMD in relation to conventional SVD markers, global measures of neurodegeneration, and cognition. 145 participants underwent 3T brain MRI and cognitive assessment. 112 were patients with mild cognitive impairment, Alzheimer's disease, progressive supranuclear palsy, dementia with Lewy bodies, or frontotemporal dementia. PSMD, SVD burden [white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), microbleeds, lacunes], average mean diffusivity (MD), gray matter (GM), white matter (WM), and total intracranial volume were quantified. Robust linear regression was conducted to examine associations between variables. Dominance analysis assessed the relative importance of markers in predicting various outcomes. Regional analyses examined spatial overlap between PSMD and WMH. PSMD was associated with global and regional SVD measures, especially WMH and microbleeds. Dominance analysis demonstrated that among SVD markers, WMH was the strongest predictor of PSMD. Furthermore, PSMD was more closely associated to WMH than with GM and WM volumes. PSMD was associated with WMH across all regions, and correlations were not significantly stronger in corresponding regions (e.g., frontal PSMD and frontal WMH) compared to non-corresponding regions. PSMD outperformed all four conventional SVD markers and MD in predicting cognition, but was comparable to GM and WM volumes. PSMD was robustly associated with established SVD markers. This new measure appears to be a marker of diffuse brain injury, largely due to vascular pathology, and may be a useful and convenient metric of overall cerebrovascular burden