Dynamics of aortic flow in hypertrophic cardiomyopathy

The purpose of this study was to reassess left ventricular ejection dynamics in hypertrophic cardiomyopathy, to investigate whether a premature stoppage of ejection occurs, as previously reported, and whether reliable criteria for left ventricular outflow tract obstruction can be established by non-invasive evaluation of aortic flow patterns. In a group of 21 patients with hypertrophic cardiomyopathy, composed of 9 with the obstructive form (HOCM), 9 with the non-obstructive form (HNCM) and 3 with apical hypertrophy (HACM), instantaneous flow velocities across the ascending aorta were determined non-invasively with a 16-gated Doppler 2-D echo instrument. Ten normals served as controls. The 16 flow velocities were averaged over 8 heart beats and the relative volume flow rate was calculated by microprocessor analysis. Ejection time (i.e. flow time) derived from the flow curves was compared with the available ejection period as determined from the carotid pulse tracing. In normals, ejection time amounted to 94±3% of the available ejection period, in HOCM to 92±5% and in HNCM to 93±4% (no significant differences). In HACM, however, ejection time was reduced to 71±14% of the available ejection period. In contrast to HNCM, aortic flow in HOCM was characterized by an early peak followed by a plateau at a sizeably lower flow level for the rest of systole. Flow time of an abnormally short duration was the hallmark of HACM. We conclude that in patients with hypertrophic cardiomyopathy, HOCM and HNCM can be distinguished by the shape of their volume flow curves. A premature stoppage of ejection is only found in patients with HAC

A comparison between single gate and multigate ultrasonic Doppler measurements for the assessment of the velocity pattern in the human ascending aorta

The velocity pattern in the ascending aorta of 15 healthy adults was measured quasisimultaneously from the Doppler-shifts produced in 16 gates distributed equally within the cross-section along a narrow ultrasound beam which centrally traversed the vessel upstream of the brachiocephalic trunk. A comparison between the time integrals of the velocities in gates 9 (centre line), 4 and 13 (off centre) and the time integral of the weighted mean of the velocities of all gates correlated with r=0.90, SEE=1.05 (gate 9), r=0.90, SEE 0.88 (gate 4) and r=0.92, SEE 0.94 (gate 13). A better correlation (r=0.96, SEE=0.60) was found between the linear mean of all gates and the weighted mean. These results show that Doppler measurements in single small gates are not appropriate to determine the average cross-sectional blood flow velocity in healthy adult

Impulse control disorders in Parkinson and RBD:a longitudinal study of severity.

Objective To describe the prevalence, natural history, and risk factors for impulse control behaviors (ICBs) among people with Parkinson disease (PD), those with REM sleep behavior disorder (RBD), and controls. Methods Participants with early PD (within 3.5 years of diagnosis), those with RBD, and controls were clinically phenotyped and screened for ICBs longitudinally (with the Questionnaire for Impulsivity in Parkinson's Disease). ICB-positive individuals were invited for a semistructured interview, repeated 1 year later. The severity of the ICB was assessed with the Parkinson's Impulse Control Scale. Multiple imputation and regression models were used to estimate ICB prevalence and associations. Results Data from 921 cases of PD at baseline, 768 cases at 18 months, and 531 cases at 36 months were included, with 21% to 25% screening positive for ICBs at each visit. Interviews of ICB screen–positive individuals revealed that 10% met formal criteria for impulse control disorders (ICD), while 33% had subsyndromal ICD (ICB symptoms without reaching the formal diagnostic criteria for ICD). When these data were combined through the use of multiple imputation, the prevalence of PD-ICB was estimated at 19.1% (95% confidence interval 10.1–28.2). On follow-up, 24% of cases of subsyndromal ICD had developed full symptoms of an ICD. PD-ICD was associated with dopamine agonist use, motor complications, and apathy but not PD-RBD. ICD prevalence in the RBD group (1%) was similar to that in controls (0.7%). Conclusions ICBs occur in 19.1% of patients with early PD, many persisting or worsening over time. RBD is not associated with increased ICD risk. Psychosocial drivers, including mood and support networks, affect severity

Equating scores of the University of Pennsylvania Smell Identification Test and Sniffin' Sticks test in patients with Parkinson's disease

BACKGROUND: Impaired olfaction is an important feature in Parkinson's disease (PD) and other neurological diseases. A variety of smell identification tests exist such as "Sniffin' Sticks" and the University of Pennsylvania Smell Identification Test (UPSIT). An important part of research is being able to replicate findings or combining studies in a meta-analysis. This is difficult if olfaction has been measured using different metrics. We present conversion methods between the: UPSIT, Sniffin' 16, and Brief-SIT (B-SIT); and Sniffin' 12 and Sniffin' 16 odour identification tests. METHODS: We used two incident cohorts of patients with PD who were tested with either the Sniffin' 16 (n = 1131) or UPSIT (n = 980) and a validation dataset of 128 individuals who took both tests. We used the equipercentile and Item Response Theory (IRT) methods to equate the olfaction scales. RESULTS: The equipercentile conversion suggested some bias between UPSIT and Sniffin' 16 tests across the two groups. The IRT method shows very good characteristics between the true and converted Sniffin' 16 (delta mean = 0.14, median = 0) based on UPSIT. The equipercentile conversion between the Sniffin' 12 and 16 item worked well (delta mean = 0.01, median = 0). The UPSIT to B-SIT conversion showed evidence of bias but amongst PD cases worked well (mean delta = -0.08, median = 0). CONCLUSION: We have demonstrated that one can convert UPSIT to B-SIT or Sniffin' 16, and Sniffin' 12 to 16 scores in a valid way. This can facilitate direct comparison between tests aiding future collaborative analyses and evidence synthesis

Statins are underused in recent-onset Parkinson's disease with increased vascular risk: findings from the UK Tracking Parkinson's and Oxford Parkinson's Disease Centre (OPDC) discovery cohorts.

BACKGROUND: Cardiovascular disease (CVD) influences phenotypic variation in Parkinson's disease (PD), and is usually an indication for statin therapy. It is less clear whether cardiovascular risk factors influence PD phenotype, and if statins are prescribed appropriately. OBJECTIVES: To quantify vascular risk and statin use in recent-onset PD, and examine the relationship between vascular risk, PD severity and phenotype. METHODS: Cardiovascular risk was quantified using the QRISK2 calculator (high ≥20%, medium ≥10 and <20%, low risk <10%). Motor severity and phenotype were assessed using the Movement Disorder Society Unified PD Rating Scale (UPDRS) and cognition by the Montreal cognitive assessment. RESULTS: In 2909 individuals with recent-onset PD, the mean age was 67.5 years (SD 9.3), 63.5% were men and the mean disease duration was 1.3 years (SD 0.9). 33.8% of cases had high vascular risk, 28.7% medium risk, and 22.3% low risk, while 15.2% of cases had established CVD. Increasing vascular risk and CVD were associated with older age (p<0.001), worse motor score (p<0.001), more cognitive impairment (p<0.001) and worse motor phenotype (p=0.021). Statins were prescribed in 37.2% with high vascular risk, 15.1% with medium vascular risk and 6.5% with low vascular risk, which compared with statin usage in 75.3% of those with CVD. CONCLUSIONS: Over 60% of recent-onset PD patients have high or medium cardiovascular risk (meriting statin usage), which is associated with a worse motor and cognitive phenotype. Statins are underused in these patients, compared with those with vascular disease, which is a missed opportunity for preventive treatment. TRIAL REGISTRATION NUMBER: GN11NE062, NCT02881099

Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies

We have developed a novel real-time quaking-induced conversion RT-QuICbased assay to detect alpha-synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson’s disease patients. This assay can detect alpha-synuclein aggregation in Dementia with Lewy bodies and Parkinson’s disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results. These results suggest that RT-QuiC analysis of cerebrospinal fluid is potentially useful for the early clinical assessment of patients with alpha-synucleinopathies

Personality and addictive behaviours in early Parkinson's disease and REM sleep behaviour disorder

INTRODUCTION: Changes in personality have been described in Parkinson's disease (PD), with suggestion that those with established disease tend to be risk averse with a disinclination for addictive behaviour. However, little is known about the earliest and prodromal stages. Personality and its relationship with addictive behaviours can help answer important questions about the mechanisms underlying PD and addiction. METHODS: 941 population-ascertained PD subjects within 3.5 years of diagnosis, 128 patients with rapid eye movement sleep behaviour disorder (RBD) and 292 control subjects were fully characterised for motor symptoms, non-motor symptoms and across the following 5 personality domains: 1) neuroticism 2) extraversion 3) conscientiousness 4) agreeableness 5) openness using the Big Five Inventory. RESULTS: Patients with early PD were more neurotic (p < 0.001), less extraverted (p < 0.001) and less open than controls (p < 0.001). RBD subjects showed the same pattern of being more neurotic (p < 0.001), less extraverted (p = 0.03) and less open (p < 0.001). PD patients had smoked less (p = 0.02) and drunk less alcohol (p = 0.03) than controls, but caffeine beverage consumption was similar. Being more extraverted (p < 0.001), more open (p < 0.001), and less neurotic (p < 0.001) predicted higher alcohol use, while being more extravert (p = 0.007) and less agreeable (p < 0.001) was associated with smoking more. CONCLUSIONS: A similar pattern of personality changes is seen in PD and RBD compared to a control population. Personality characteristics were associated with addictive behaviours, suggestive of a common link, but the lower rates of addictive behaviours before and after the onset of motor symptoms in PD persisted after accounting for personality

Smartphone motor testing to distinguish idiopathic REM sleep behavior disorder, controls, and PD

OBJECTIVE: We sought to identify motor features that would allow the delineation of individuals with sleep study-confirmed idiopathic REM sleep behavior disorder (iRBD) from controls and Parkinson disease (PD) using a customized smartphone application. METHODS: A total of 334 PD, 104 iRBD, and 84 control participants performed 7 tasks to evaluate voice, balance, gait, finger tapping, reaction time, rest tremor, and postural tremor. Smartphone recordings were collected both in clinic and at home under noncontrolled conditions over several days. All participants underwent detailed parallel in-clinic assessments. Using only the smartphone sensor recordings, we sought to (1) discriminate whether the participant had iRBD or PD and (2) identify which of the above 7 motor tasks were most salient in distinguishing groups. RESULTS: Statistically significant differences based on these 7 tasks were observed between the 3 groups. For the 3 pairwise discriminatory comparisons, (1) controls vs iRBD, (2) controls vs PD, and (3) iRBD vs PD, the mean sensitivity and specificity values ranged from 84.6% to 91.9%. Postural tremor, rest tremor, and voice were the most discriminatory tasks overall, whereas the reaction time was least discriminatory. CONCLUSIONS: Prodromal forms of PD include the sleep disorder iRBD, where subtle motor impairment can be detected using clinician-based rating scales (e.g., Unified Parkinson's Disease Rating Scale), which may lack the sensitivity to detect and track granular change. Consumer grade smartphones can be used to accurately separate not only iRBD from controls but also iRBD from PD participants, providing a growing consensus for the utility of digital biomarkers in early and prodromal PD

Effects of N-acetyl-cysteine on endothelial function and inflammation in patients with type 2 diabetes mellitus

Endothelial dysfunction has been associated with premature vascular disease. There is increasing data that N-acetyl-cysteine (NAC) may prevent or improve endothelial dysfunction. The aim of this study was to assess the effects of NAC on endothelial function in patients with type 2 diabetes mellitus, a population at high risk for endothelial dysfunction. Twenty-four patients with diabetes mellitus were assigned randomly to initial therapy with either 900 mg NAC or placebo twice daily in a double-blind, cross-over study design. Flowmediated vasodilation (FMD) of the brachial artery was assessed at baseline, after four weeks of therapy, after a four-week wash-out period, and after another four weeks on the opposite treatment. Plasma and red blood cell glutathione levels and high-sensitivity C-reactive protein (CRP) were measured at all four visits. At baseline, FMD was moderately impaired (3.7±2.9%). There was no significant change in FMD after four weeks of NAC therapy as compared to placebo (0.1±3.6% vs. 1.2±4.2%). Similarly, there was no significant change in glutathione levels. However, median CRP decreased from 2.35 to 2.14 mg/L during NAC therapy (p=0.04), while it increased from 2.24 to 2.65 mg/L with placebo. No side effects were noted during the treatment period. In this double-blind, randomized cross-over study, four weeks of oral NAC therapy failed to improve endothelial dysfunction in patients with diabetes mellitus. However, NAC therapy decreased CRP levels, suggesting that this compound may have some efficacy in reducing systemic inflammation