Recent developments in genetics and medically assisted reproduction : from research to clinical applications

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.Peer reviewe

A systematic review of MEG-based studies in Parkinson's disease: The motor system and beyond

Parkinson's disease (PD) is accompanied by functional changes throughout the brain, including changes in the electromagnetic activity recorded with magnetoencephalography (MEG). An integrated overview of these changes, its relationship with clinical symptoms, and the influence of treatment is currently missing. Therefore, we systematically reviewed the MEG studies that have examined oscillatory activity and functional connectivity in the PD-affected brain. The available articles could be separated into motor network-focused and whole-brain focused studies. Motor network studies revealed PD-related changes in beta band (13–30 Hz) neurophysiological activity within and between several of its components, although it remains elusive to what extent these changes underlie clinical motor symptoms. In whole-brain studies PD-related oscillatory slowing and decrease in functional connectivity correlated with cognitive decline and less strongly with other markers of disease progression. Both approaches offer a different perspective on PD-specific disease mechanisms and could therefore complement each other. Combining the merits of both approaches will improve the setup and interpretation of future studies, which is essential for a better understanding of the disease process itself and the pathophysiological mechanisms underlying specific PD symptoms, as well as for the potential to use MEG in clinical care

search strategy appendix 2

search strategy appendix

Clinical correlates of quantitative EEG in Parkinson disease: A systematic review

OBJECTIVE: To assess the relevance of quantitative EEG (qEEG) measures as outcomes of disease severity and progression in Parkinson disease (PD). METHODS: Main databases were systematically searched (January 2018) for studies of sufficient methodologic quality that examined correlations between clinical symptoms of idiopathic PD and cortical (surface) qEEG metrics. RESULTS: Thirty-six out of 605 identified studied were included. Results were classified into 4 domains: cognition (23 studies), motor function (13 studies), responsiveness to interventions (7 studies), and other (10 studies). In cross-sectional studies, EEG slowing correlated with global cognitive impairment and with diffuse deterioration in other domains. In longitudinal studies, decreased dominant frequency and increased θ power, reflecting EEG slowing, were biomarkers of cognitive deterioration at an individual level. Results on motor dysfunction and treatment yielded contrasting findings. Studies on functional connectivity at an individual level and longitudinal studies on other domains or on connectivity measures were lacking. CONCLUSION: qEEG measures reflecting EEG slowing, particularly decreased dominant frequency and increased θ power, correlate with cognitive impairment and predict future cognitive deterioration. qEEG could provide reliable and widely available biomarkers for nonmotor disease severity and progression in PD, potentially promoting early diagnosis of nonmotor symptoms and an objective monitoring of progression. More studies are needed to clarify the role of functional connectivity and network analyses

Quantitative EEG reflects non-dopaminergic disease severity in Parkinson's disease

OBJECTIVE: In Parkinson's Disease (PD), measures of non-dopaminergic systems involvement may reflect disease severity and therefore contribute to patient-selection for Deep Brain Stimulation (DBS). There is currently no determinant for non-dopaminergic disease severity. In this exploratory study, we investigated whether quantitative EEG reflects non-dopaminergic disease severity in PD. METHODS: Sixty-three consecutive PD patients screened for DBS were included (mean age 62.4 ± 7.2 years, 32% females). Relative spectral powers and the Phase-Lag-Index (PLI) reflecting functional connectivity were analysed on routine EEGs. Non-dopaminergic disease severity was quantified using the SENS-PD score and its subdomains; motor-severity was quantified using the MDS-UPDRS III. RESULTS: The SENS-PD composite score correlated with a spectral ratio ((δ + θ)/(α1 + α2 + β) powers) (global spectral ratio Pearson's r = 0.4, 95% Confidence Interval (95%CI) 0.1-0.6), and PLI in the α2 band (10-13 Hz) (r = -0.3, 95%CI -0.5 to -0.1). These correlations seem driven by the subdomains cognition and psychotic symptoms. MDS-UPDRS III was not significantly correlated with EEG parameters. CONCLUSIONS: EEG slowing and reduced functional connectivity in the α2 band were associated with non-dopaminergic disease severity in PD. SIGNIFICANCE: The described EEG parameters may have complementary utility as determinants of non-dopaminergic involvement in PD

Supplementary tables

Supplementary table 1: Correlation of qEEG and cognition; Supplementary table 2: Longitudinal assessments; Supplementary table 3: Motor function; Supplementary table 4: Treatment; Supplementary table 5: Othe

Risk of bias assessment appendix 4

Risk of bias assessment appendix

Data from: Clinical correlates of quantitative EEG in Parkinson’s disease: a systematic review

OBJECTIVE To assess the relevance of Quantitative electroencephalography (qEEG) measures as outcomes of disease severity and progression in PD. METHODS Main databases were systematically searched (January 2018) for studies of sufficient methodological quality that examined correlations between clinical symptoms of idiopathic PD and cortical (surface) qEEG metrics. RESULTS Thirty-six out of 605 identified studied were included. Results were classified into four domains: cognition (23 studies), motor function (13 studies), effect of treatment (7 studies), and other (10 studies). In cross-sectional studies, EEG slowing correlated with global cognitive impairment and with diffuse deterioration in other domains. In longitudinal studies, decreased dominant frequency and increased θ power, reflecting EEG slowing, were biomarkers of cognitive deterioration at an individual level. Results on motor dysfunction and treatment yielded contrasting findings. Studies on functional connectivity at an individual level, longitudinal studies on other domains or on connectivity measures, were lacking. CONCLUSION QEEG parameters reflecting EEG slowing, particularly decreased dominant frequency and increased θ power, correlate with cognitive impairment and predict future cognitive deterioration. QEEG could provide reliable and widely available biomarkers for non-motor disease severity and progression in PD, potentially promoting early diagnosis of non-motor symptoms and an objective monitoring of progression. More studies are needed to clarify the role of functional connectivity and network analyses