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Background and Purpose Pure autonomic failure (PAF) presents primarily as cardiovascular autonomic failure and may phenoconvert to other neurodegenerative disorders. However, the involvement of other autonomic functions has been poorly evaluated. This study aims to characterize genitourinary and bowel dysfunction and explore their relationship with cardiovascular autonomic dysfunction. Methods Pure autonomic failure patients underwent cardiovascular autonomic testing and an assessment of pelvic autonomic dysfunction using urinary, sexual symptoms questionnaires and a bladder diary. Demographic, clinical features and related medical comorbidities were assessed. Results Twenty‐five patients (10 males) with PAF were included (mean age 71 ± 8 years; disease duration 13 ± 8 years). 96% (24/25) reported lower urinary tract symptoms, of which overactive bladder symptoms were most commonly reported (n = 23; 92%; median overactive subscore 8, interquartile range [IQR] 3–11), followed by voiding difficulties (n = 19; 76%; median low stream subscore 2, IQR 1–3) using the Urinary Symptom Profile; however, only four (16%) required clean intermittent self‐catheterization. Sexual dysfunction was common (n = 21; 84%) using the Arizona Sexual Experience Scale. Mild faecal incontinence and constipation were reported. 86% (19/22) had nocturnal polyuria (NP) and the median NP index was 47% (IQR 38%–51%; normal range <33%). 77% (10/13) had voiding dysfunction and 31% (4/13) had post‐void residual urine >100 mL. There were no significant correlations between the need for catheterization and the degree of NP with age, disease duration and cardiovascular autonomic parameters (p > 0.05). Conclusions Nocturnal polyuria, genitourinary and bowel symptoms are commonly seen in PAF. The pathophysiology of NP in PAF is most likely multifactorial and may occur independent of cardiovascular autonomic failure.

BackgroundHereditary transthyretin amyloidosis (ATTR) is usually characterised by a progressive peripheral and autonomic neuropathy often with associated cardiac failure and is due to dominantly inherited transthyretin mutations causing accelerated amyloid deposition. The UK population is unique in that the majority of patients have the T60A missense mutation in ATTR where tyrosine is replaced by adenine at position 60. This has been traced to a single founder mutation from north-west Ireland. The neuropathy phenotype is less well described than the cardiac manifestations in this group.MethodsWe present the findings from an observational cohort study of patients with ATTR attending the National Hospital Inherited Neuropathy Clinic between 2009 and 2013. Detailed clinical neurological and electrophysiological data were collected on all patients alongside correlating autonomic and cardiac assessments. Follow-up data were available on a subset.ResultsForty-four patients with genetically confirmed ATTR were assessed; 37 were symptomatic; mean age at onset=62 years, range=38–75 years; 75.7% male. T60A was the most common mutation (17/37), followed by V30M (5/37). A severe, rapidly progressive, predominantly length dependent axonal sensorimotor neuropathy was the predominant phenotype. T60A patients were distinguished by earlier and more frequent association with carpal tunnel syndrome; a predominance of negative sensory symptoms at onset; significant vibration deficits; and a non-length dependent progression of motor deficit. Progression of the neuropathy was observed over a relatively short follow-up period (2 years) in 20 patients with evidence of clinically measurable annual change in Medical Research Council (MRC) sum score (–1.5 points per year) and Charcot Marie Tooth Neuropathy Score (CMTNS:2.7 points per year), and a congruent trend in the electrophysiological measures used.ConclusionThe description of the ATTR neuropathy phenotype, especially in the T60A patients, should aid early diagnosis as well as contribute to the understanding of its natural history.

Carers of 69 patients with dementia: 28 behavioural-variant FTD (bvFTD; 10 female (F), 18 male (M)), 20 semantic dementia (SD; 9 F, 11 M), 21 Alzheimer's disease (AD; 10 F, 11 M) from the FTD clinic at Neuroscience Research Australia, completed the Autonomic Symptoms Questionnaire (ASQ), which comprises 44 questions that examine physical symptoms related to autonomic functions including blood pressure/cardiovascular function, gastrointestinal, temperature regulation and sweating, urinary symptoms and sleep. [...]many of the symptoms elicited in our survey cause significant distress to patients and their carers, and may be overlooked.

Background Pure autonomic failure (PAF) presents with autonomic failure without other neurological features. A third develop central neurological features, fulfilling criteria for multiple system atrophy (MSA) and Lewy body diseases (LBD), including Parkinson's disease and Dementia with Lewy bodies. We hypothesized multimodal autonomic biomarkers would identify differences between PAF, MSA, and LBD, and predict phenoconversion in patients presenting with PAF. Methods This observational cohort study included 391 alpha‐synucleinopathy patients evaluated with cardiovascular autonomic testing, plasma noradrenaline, pupillometry, autonomic symptom, and quality‐of‐life questionnaires. PAF patients were monitored for the emergence of central neurological features. Logistic regression modeling was used to identify autonomic biomarkers at initial assessment that predicted future phenoconversion. Results Patients with PAF had more severe orthostatic hypotension, lower supine plasma noradrenaline, and frequent sympathetic pupillary deficits at initial assessment than MSA and LBD. 50/194 (26%) with PAF phenoconverted to MSA or LBD after a median of 13 years, with normal pupils, heart rate response to deep breathing ≥ 10 bpm, and supine plasma noradrenaline ≥ 200 pg/mL predicting future phenoconversion to MSA or LBD, with younger age at presentation and higher supine plasma noradrenaline levels associated with conversion to MSA. Conclusion In patients presenting with PAF, normal pupillary function and supine plasma noradrenaline levels with intact cardiovagal responses were red flags for future phenoconversion. Younger patients with higher supine plasma noradrenaline levels were more likely to convert to MSA rather than LBD. A non‐invasive multimodal autonomic assessment can help differentiate between alpha‐synucleinopathies and predict phenoconversion from PAF to MSA or LBD.

Nuclear medicine offers several techniques and procedures to image infection, but radiolabelled autologous white blood cells (WBCs) are still the gold standard. These cells are usually labelled with 111 In or 99m Tc bound to a hydrophobic chelating agent that allows these isotopes to pass through the plasma membrane and enter in the cytoplasm. The most common compound in Europe is HMPAO that efficiently chelates 99m Tc. However, up to 20–40% of the complex is released from the cells in the first few hours. The aim of this study was to radiolabel a new compound, (S 3 CPh) 2 (S 2 CPh)-complex (SSS-complex) with 99m Tc and compare its binding kinetics and specificity for WBC with HMPAO. The SSS-complex was labelled with 99m Tc and analysed by iTLC and RP-HPLC. In vitro quality controls included a stability assay in serum and saline. Results showed a labelling efficiency of 95 ± 1.2% and 98 ± 1.4% for 99m Tc-SSS-complex and 99m Tc-HMPAO, respectively ( p = n s ). 99m Tc-SSS-complex was stable in serum and in saline up to 24 h (94 ± 0.1%). Cell labelling experiments showed a higher incorporation of 99m Tc-SSS-complex than 99m Tc-HMPAO by granulocytes (62.6 ± 17.8% vs 40.5 ± 15%, p = 0.05 ), lymphocytes (59.9 ± 22.2% vs 29.4 ± 13.5%; p = 0.03 ), and platelets (44.4 ± 24% vs 20.5 ± 10.7%; p = n s ), but the release of radiopharmaceutical from granulocytes at 1 h was lower for HMPAO than for SSS-complex (10.3 ± 1.9% vs 21.3 ± 1.8%; p = 0.001 ). In conclusion, 99m Tc-SSS-complex, although showing high labelling efficiency, radiochemical purity, and stability, is not a valid alternative to 99m Tc-HMPAO, for example, in vivo white blood cells labelling because of high lymphocyte and platelet uptake and rapid washout from granulocytes.

Objective To test the hypothesis that Joint hypermobility and autonomic dysfunction are over-expressed within neurodevelopmental disorders. Joint hypermobility is a widespread poorly recognized connective tissue condition with affected individuals overrepresented among panic and anxiety disorders, irritable bowel syndrome, fibromyalgia, and chronic fatigue. The relevance of hypermobility to neuropsychiatric disorders of developmental origin is currently unknown, despite anecdotal case reports and clinical suspicion of a link. Autonomic nervous system dysregulation, typically postural tachycardia syndrome is often found in hypermobile individuals. Interestingly, differences in amygdala and superior temporal cortex anatomy have been reported in hypermobile populations and functional abnormalities in patients with autism. Method Thirty-seven adults with neurodevelopmental disorder, 205 patients attending general psychiatric clinics without neurodevelopmental diagnosis and 29 healthy controls were recruited. Hypermobility was assessed using the Beighton scale (BS) and autonomic symptoms using the Autonomic Symptoms and Quality of Life Score (ASQoLS: orthostatic, gastrointestinal, bladder, secretomotor, sudomotor and sleep domains. Results The neurodevelopmental cohort had a mean age of 34.6 years (27 male). Nineteen had Attention Deficit Hyperactivity Disorder (ADHD), 4 Autistic Spectrum Disorder (ASD), 1 Tourette Syndrome (TS) and the remainder combinations of ADHD, ASD and TS. Nine had co-morbid affective disorder. Eighteen patients (48.6%) were classified as hypermobile (BS>=4) compared to 67/204(32.7%) in the general psychiatric group (p=0.048) and 3/29(10.3%) in healthy controls (p=0.007) and this prevalence was also significantly higher that reported in a large general population cohort (1156/6022, 19.19%, p=<0.001). Mean autonomic dysfunction score was significantly higher in the neurodevelopmental cohort compared to controls (mean±SEM: neurodevelopmental disorder patients, 45.8±4.86; controls, 8.5±1.62). This effect was seen across all sub-scales of the ASQoLS. Total autonomic dysfunction score did not differ significantly between neurodevelopmental cohort and the general psychiatric group, however neurodevelopmental disorder patients had significantly higher scores on orthostatic and gastrointestinal disturbance subscales. Conclusion We demonstrate for the first time that rates of hypermobility and symptoms of autonomic dysfunction are particularly high in adults with neurodevelopmental diagnoses. It is likely that the importance of hypermobility and autonomic dysfunction to the generation and maintenance of psychopathology in neurodevelopmental disorders is poorly appreciated. Work underway(autonomic testing, fMRI) will test the hypothesis that autonomic reactivity and interoceptive sensitivity predispose to the expression of psychiatric symptoms, particularly anxiety. It is further hypothesized that inefficient neural co-ordination of efferent autonomic drive with imprecise interoceptive representations may be amplified in hypermobile individuals. In hypermobility, this mechanism might explain increased vulnerability to stress sensitive and developmental neuropsychiatric conditions.

Nuclear medicine offers several techniques and procedures to image infection, but radiolabelled autologous white blood cells (WBCs) are still the gold standard. These cells are usually labelled with 111In or 99mTc bound to a hydrophobic chelating agent that allows these isotopes to pass through the plasma membrane and enter in the cytoplasm. The most common compound in Europe is HMPAO that efficiently chelates 99mTc. However, up to 20–40% of the complex is released from the cells in the first few hours. The aim of this study was to radiolabel a new compound, (S3CPh)2 (S2CPh)-complex (SSS-complex) with 99mTc and compare its binding kinetics and specificity for WBC with HMPAO. The SSS-complex was labelled with 99mTc and analysed by iTLC and RP-HPLC. In vitro quality controls included a stability assay in serum and saline. Results showed a labelling efficiency of 95 ± 1.2% and 98 ± 1.4% for 99mTc-SSS-complex and 99mTc-HMPAO, respectively (p=ns). 99mTc-SSS-complex was stable in serum and in saline up to 24 h (94 ± 0.1%). Cell labelling experiments showed a higher incorporation of 99mTc-SSS-complex than 99mTc-HMPAO by granulocytes (62.6 ± 17.8% vs 40.5 ± 15%, p=0.05), lymphocytes (59.9 ± 22.2% vs 29.4 ± 13.5%; p=0.03), and platelets (44.4 ± 24% vs 20.5 ± 10.7%; p=ns), but the release of radiopharmaceutical from granulocytes at 1 h was lower for HMPAO than for SSS-complex (10.3 ± 1.9% vs 21.3 ± 1.8%; p=0.001). In conclusion, 99mTc-SSS-complex, although showing high labelling efficiency, radiochemical purity, and stability, is not a valid alternative to 99mTc-HMPAO, for example, in vivo white blood cells labelling because of high lymphocyte and platelet uptake and rapid washout from granulocytes.

In people living with HIV infection (PLWH), the risk of developing cardiovascular comorbidity is significantly higher than in uninfected population, despite the virosoppression of HIV. The chronic inflammation and immune activation associated to HIV disease may promote the mechanisms that lead to atherosclerotic plaque formation, thus increasing the risk of CVD in these individuals. Whether the prevalence of subclinical atherosclerosis is even higher in PLWH is unclear. The aim of the study is to improve the risk stratification for cardiovascular events in people living with HIV, through the simultaneous evaluation of carotid and femoral IMT. Fifty-five HIV-positive patients, permanently virosoppressed with effective STR regimens, were scanned for IMT measurement, by vascular ultrasound of four vascular beds (right-left carotid artery and right-left femoral artery). For the study of the common femoral axis we analyzed the last portion of the vessel upstream of the bifurcation. All sonographic measurements were performed using a high resolution B-mode US with a 12-MHz linear transducer, by a single experienced investigator. All patients were assessed for both carotid and femoral intima media thickness (c-IMT and f-IMT) and for the presence of atherosclerotic plaques; and underwent blood tests at the time of instrumental evaluation. The IMT was defined as the distance between the media-adventitia interface and the lumen-intima interface. The presence of plaque was defined as a focal protrusion into the lumen >0.5 mm or IMT >1.5 mm. Patients were evaluated for cardiovascular risk factors, indices of cardiometabolic and vascular function (blood pressure, BMI). Demographics, HIV characteristics, cardiovascular risk factors and estimations are summarized in tables 1 and 2. For statistical analysis we used the test t-student and Chi square test. Doppler analysis showed atheromatous plaques were more prevalent in the carotid axis than in the femoral axis (c-Plaque= 34.45% - 36/55 vs f-Plaque=12.72% - 7/55; p=0.0136). Regarding lipid profile, patients with c-plaque show significantly higher levels of total cholesterol (p=0,03), LDL-cholesterol (p=0,024) and% cholesterol >200 mg/dl (p=0,046) than those without plaque. Significantly higher total serum cholesterol values was also observed in f-plaque patients versus those without plaques (p=0,045). Concerning the relationship, plaque – cardiovascular risk estimator, the high risk of CV events with the use European score equation, is statistically significant in patients with c- plaque (p=0,008). No significant correlation was found between plaque and the Framingham risk score for risk prediction A statistically significant relationship was low CV risk in ASCVD and the absence of both carotid and femoral plaque (p=0,06 and p=0,046). The analysis of our data confirms that the control of cardiometabolic risk factors and the use of CV risk estimators prevent the clinical manifestations of CV comorbidity.Abstract P13 Table 1Abstract P13 Table 2

IntroductionCardiovascular Diseases have emerged as a leading cause of morbidity and mortality in patients with HIV (PLWH). Several studies on the general population have reported a relationship between higher carotid Intima Media Thickness (c-IMT), a measure of subclinical atherosclerosis (SAT), and hepatic steatosis (HS). However, few data are available on the relationship between SAT and HS in HIV subjects and it is unclear how the role of chronic inflammation markers, such as the CD4/CD8 ratio and nadir CD4 count, could be drivers in atherogenesis process. Therefore, objective of our study is to evaluate this relationships in a cohort of PLWH not coinfected for viral hepatitis.Patients and MethodsIn this observational, retrospective, cross-sectional study we enrolled 184 patients, 52 females and 132 males. We divided the patients in 2 groups based on cIMT: A) (#118) with normal cIMT(<1.3 mm) and B)(#66) with pathologic cIMT (>1.3 mm). Patients were submitted to measurement of carotid intima-media thickness (cIMT) with high resolution B mode Doppler USG and evaluation of HF using a process based on vibration-controlled transient elastography (Fibroscan) and HS by an ultrasonic controlled attenuation parameter (CAP). The cut-off value for defining the presence of c-IMT is 1,3 mm, for significant HS is CAP > 260 dBm and for liver fibrosis is > 7 kPa. For each group we also considered the body mass index (overweight >25 kg/m2), alcohol abuse (>2 alcohol units in a day for men and > 1 alcohol unit for women), current CD4 value, CD4 nadir, CD4/CD8 ratio, years on HAART, type of ART, total, HDL and LDL cholesterol and triglycerides levels. For statistical analysis we used t-student and X-square tests.ResultsResults are shown in table 1. We observed a significant difference in the two groups in alcohol intake, indeed, patients in group B have current and history of alcohol abuse. No significant differences emerged between the two groups regarding current CD4, LDL, triglycerides and HDL values. A significant difference emerged for nadir CD4, CD4/CD8 ratio, and total cholesterol. Patients with c-IMT>1,3 have been associated with higher steatosis levels (p<0,004).Abstract SC12 Table 1ConclusionsOur data confirm a strong correlation between liver steatosis and subclinical atherosclerosis in PLWH. Moreover, modifiable risk factors (total cholesterol and triglycerides), markers of chronic inflammation (CD4+ nadir and CD4/CD8 ratio<1), and alcohol abuse play a role in the development of intima-media changes. Furthermore, it seems that some antiretroviral regimes, could be more ‘protective’ than others in plaque development. Finally, these data suggest the importance and need for broader diagnostic evaluation in PLWHs.

IntroductionCardiovascular Diseases have emerged as a leading cause of morbidity and mortality in patients HIV positive (PLWH). Several studies have reported higher carotid Intima Media Thickness (c-IMT), a measure of subclinical atherosclerosis, in these patients and a correlation with hepatic steatosis (HS). Only few studies have evaluated the interaction between c-IMT and hepatic fibrosis (HF).Patients and MethodsWe enrolled 128 patients, 33 females and 95 males. We divided the patients in 2 groups based on cIMT: A) (#85) with normal cIMT(<1.3 mm) and B)(#43) with pathologic cIMT (>1.3 mm). Patients were submitted to measurement of carotid intima-media thickness (cIMT) with high resolution B mode Doppler USG and evaluation of HF using a process based on vibration-controlled transient elastography (Fibroscan) and HS by an ultrasonic controlled attenuation parameter (CAP). The cut-off value for defining the presence of c-IMT is 1,3 mm, for significant HS is CAP > 260 dBm and for liver fibrosis is > 7 kPa. For each group we also considered CD4, CD4 nadir, CD4/CD8 ratio, years of HAART, type of ART, total, HDL and LDL cholesterol and triglycerides levels. For statistical analysis we used t-student and X-square tests.ResultsResults are shown in table 1. No significant differences emerged between the two groups regarding CD4 and HDL values. A significant difference emerged for nadir CD4, CD4/CD8 ratio, triglycerides, total cholesterol, HDL and LDL. Patients with c-IMT>1,3 have been associated with higher steatosis levels (p<0,004) and with tendentially higher fibrosis (although not statistically significant, p 0,09).ConclusionsThese data show a correlation between liver and endothelial damage in PLWH in ART: patients with cIMT>1.3 mm more often show liver steatosis. Moreover, it would seem that the antiretroviral regimen plays a decisive role in the development of comorbidities based on the alteration of lipid metabolism. However, these data suggest the importance and need for broader diagnostic evaluation in PLWHs.Abstract SC-21 Table 1Results