Dopamine Receptors in Parkinson's Disease: A Meta-Analysis of Imaging Studies

AbstractDopamine receptors are abundant along the central nigrostriatal tract and are expressed as 5 subtypes in two receptor families. In PD, compensatory changes in dopamine receptors emerge as a consequence of the loss of dopamine nerve terminals or dopaminergic pharmacotherapy. We performed a systematic review and meta‐analysis of the available PET and single‐photon emission computed tomography studies that have investigated dopamine receptors in PD, PSP and MSA. The inclusion criteria were studies including human PET or single‐photon emission computed tomography imaging; dopamine receptor tracers (D1‐like or D2‐like) and idiopathic PD, PSP, or MSA patients compared with healthy controls. The 67 included D2‐like studies had 1925 patients. Data were insufficient for an analysis of D1‐like studies. PD patients had higher striatal binding early in the disease, but after a disease duration of 4.36 years, PD patients had lower binding values than healthy controls. Striatal D2R binding was highest in unmedicated early PD patients and in the striatum contralateral to the predominant motor symptoms. PSP and MSA‐P patients had lower striatal D2R binding than PD patients (14.2% and 21.8%, respectively). There is initial upregulation of striatal D2Rs in PD, which downregulate on average 4 years after motor symptom onset, possibly because of agonist‐induced effects. The consistent upregulation of D2Rs in the PD striatum contralateral to the predominant motor symptoms indicates that receptor changes are driven by neurodegeneration and loss of striatal neuropil. Both PSP and MSA patients have clearly lower striatal D2R binding values than PD patients, which offers an opportunity for differential diagnostics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Time-course of left ventricle function during mild therapeutic hypothermia in out-of-hospital cardiac arrest patients

Peer reviewe

Repeated cobalt and chromium ion measurements in patients with large-diameter head metal-on-metal ReCap-M2A-Magnum total hip replacement

Background and purpose - Whole blood (WB) cobalt (Co) and chromium (Cr) ion levels have a major role in the follow-up of metal-on-metal total hip replacement (MoM THR). We investigated, first, if there was a change in WB Co or Cr levels over repeated measurements in patients with ReCap-M2A-Magnum THR, and, second, determined how many patients had WB Co or Cr levels that exceeded the safe upper limits (SUL) in the repeated whole blood metal ion assessment. Patients and methods - A Recap-M2A-Magnum THR was used in 1,329 operations (1,188 patients) at our institution between 2005 and 2012. We identified all patients (n = 319) with unilateral ReCap-M2A-Magnum implants who had undergone at least 2 repeated metal ion measurements with the first blood sample taken mean 5.5 years (1.8-9.3) after surgery and the second taken mean 2 years (0.5-3) after the first. Results - The median WB Co and Cr ion levels decreased in repeated measurements from 1.40 (0.40-63) ppb to 1.10 (0.20-68) ppb and from 1.60 (0.60-13.0) ppb to 1.10 (0.30-19.0) ppb, respectively. 7% of the Co ion values exceeded SUL at the initial measurement, and 7% at the control measurement. The proportion of Cr ion values exceeding the safe upper limit (SUL) decreased during the measurement interval from 5% to 4%. Interpretation - Repeated metal ion measurements in unilateral ReCap-M2A-Magnum patients in a mean 2-year time interval did not show any increase. Long-term ion levels are, however, not yet known

Efficacy of inhaled salbutamol with and without prednisolone for first acute rhinovirus-induced wheezing episode

Background Acute rhinovirus-induced wheezing is common in young children and may respond to systemic corticosteroid. There are no trials on the efficacy of inhaled beta(2)-agonist in this clinical scenario. Objective To study post hoc the short-term (up to 2 months) efficacy of inhaled beta(2)-agonist with and without oral corticosteroid in the first acute rhinovirus-induced severe wheezing episode in young hospitalized children. Methods The study population came from two randomized controlled trials comparing oral prednisolone (2 mg/kg/d for 3 days) to placebo: Vinku (n = 35, NCT00494624) used high-dose regular nebulized salbutamol (0.15 mg/kg 2-4 h intervals) and Vinku2 (n = 60, NCT00731575, EudraCT 2006-007100-42) used inhaled salbutamol on-demand. Both studies used identical detailed follow-up assessments. The primary outcome of the former was the duration of hospitalization and of the latter the occurrence of and the time to a new physician-confirmed wheezing episode within 2 months after discharge. Treatment groups included salbutamol high-dose vs. salbutamol on-demand while adjusting for prednisolone status and acknowledging for interactions with exception of the duration of hospitalization in which prednisolone groups could not be fully used due to protocol differences. Results Median age of subjects was 13 months, 32% were sensitized and 22% had doctor-diagnosed eczema. In the duration of hospitalization, salbutamol high-dose/placebo versus salbutamol on-demand/placebo groups did not differ (p = .12). In the occurrence of and time to relapse within 2 months, a significant group x treatment interaction was observed (both p = .02), such that high-dose group had less and longer time to relapses than on-demand group in prednisolone arm (both p .26). Conclusions In young, hospitalized children with first episode of rhinovirus-induced wheezing, high-dose inhaled salbutamol may interact with oral prednisolone. However, further trials are warranted.Peer reviewe

Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

IMPORTANCE: Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE: To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized. INTERVENTIONS: Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group). MAIN OUTCOMES AND MEASURES: The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months. RESULTS: Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053). CONCLUSIONS AND RELEVANCE: Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00879892

The effect of an active video game intervention on physical activity, motor performance, and fatigue in children with cancer: a randomized controlled trial

ObjectiveTo evaluate the effect of active video games in promoting physical activity and motor performance, and reducing fatigue in children with cancer. A randomized controlled trial was conducted. The intervention included playing Nintendo Wii™Fit (Nintendo Co., Ltd., Kyoto, Japan) for 30 min/day for 8 weeks. Physical activity was estimated with accelerometers, physical activity diaries and questionnaires. Movement-ABC2 and PedsQL™ were used to examine motor performance and fatigue. Intervention experiences and fidelity were examined with an interview.ResultsParticipants (n = 36 children with cancer, 3–16 years-old) were randomly assigned to the intervention and control groups. The median [min–max] accelerometer counts/h (500 [131–1130] vs 385 [116–1012], p = 0.63) and physical activity min/day (34 [0–150] vs 23 [0–260], p = 0.95) did not differ between the groups. Change between the pre-test and post-test regarding motor performance and fatigue was similar in both groups (motor performance p = 0.77; fatigue p = 1.00). Participants experienced playing active video games meaningful, but the intervention was not followed completely as instructed. Overall, the physical activity levels were low and one fourth of the children had or were at risk of having movement difficulties.</p

Neurofibromatosis type 1 of the child increases birth weight

Neurofibromatosis type 1 (NF1) is associated with reduced adult height, but there are no cohort studies on birth size. This retrospective study includes a cohort of 1,410 persons with NF1 and a matched comparison cohort from the general population. Figures for birth size were retrieved from the administrative registers of Finland, and the data were converted to standard deviation scores (SDS), defined as standard deviation difference to the reference population. The birth weight among infants with NF1 was higher than among infants without the disorder (adjusted mean difference [95% confidence interval]: 0.53 SDS [0.19-0.87]), as was the head circumference at birth (0.58 SDS [0.26-0.90]). The birth length of the NF1 infants did not differ significantly from the comparison cohort. The birth weight in the group consisting of NF1 and non-NF1 infants of NF1 mothers was lower than among infants of mothers in the comparison cohort (-0.28 SDS [-0.51 to -0.06]), as was the birth length (-0.22 SDS [-0.45 to 0.00]). In conclusion, the birth weight and head circumference of persons with NF1 are significantly higher than those of persons without the disorder. NF1 of the mother reduces birth weight and birth length of the infant.Peer reviewe

Congenital anomalies in neurofibromatosis 1: a retrospective register-based total population study

Background: Neurofibromatosis type 1 (NF1) is a dominantly inherited Rasopathy caused by mutations in the NF1 gene on chromosome 17. NF1 has been connected to congenital anomalies, e.g., in the skeletal and cardiovascular systems, but the overall incidence of anomalies is unknown. In this retrospective register-based total population study conducted in Finland, the congenital anomalies in NF1 were evaluated.Methods: One thousand four hundred ten patients with NF1 were identified by searching the medical records related to inpatient and outpatient hospital visits of patients with an associated diagnosis for NF1 in 1987-2011. Each diagnosis was confirmed by a thorough review of the medical records. Ten non-NF1 control persons per NF1 patient were collected from the Population Register Centre. NF1 patients and controls were linked to the Medical Birth Register and the Register of Congenital Malformations. Odds ratios (OR) and 95% confidence intervals (95% CI) for major congenital anomalies (MCA) were calculated.Results: The OR for at least one MCA among NF1 children was almost threefold (adjusted OR 2.78, 95% CI 1.71-4.54) compared to controls matched for age, sex and municipality. NF1 children had a significantly increased risk of congenital anomalies in the circulatory (adjusted OR 3.35, 95% CI 1.64-6.83), urinary (adjusted OR 4.26, 95% CI 1.36-13.35) and musculoskeletal (adjusted OR 2.77, 95% CI 1.09-7.02) systems. Also, anomalies of the eye, ear, head and neck were more common among NF1 children than controls (adjusted OR 4.66, 95% CI 1.42-15.31). Non-NF1 children of mothers with NF1 did not have more anomalies than controls (adjusted OR 0.53, 95% CI 0.13-2.21).Conclusions: Children with NF1 have more MCAs than controls and close follow-up during pregnancy and the neonatal period is required if the mother or father has NF1. Non-NF1 children of mothers with NF1 do not have an increased risk for anomalies