Gene-environment interaction and Mendelian randomisation.

Genetic factors only account for up to a third of the cases of Parkinson's disease (PD), while the remaining cases are of unknown aetiology. Environmental exposures (such as pesticides or heavy metals) and the interaction with genetic susceptibility factors (summarized in the concept of impaired xenobiotic metabolism) are believed to play a major role in the mechanisms of neurodegeneration. Beside of the classical association studies (e.g. genome-wide association studies), a novel approach to investigate environmental risk factors are Mendelian randomisation studies. This review explores the gene-environment interaction and the gain of Mendelian randomisation studies in assessing causalities of modifiable risk factors for PD.

Lateralisation in Parkinson disease.

Asymmetry of dopaminergic neurodegeneration and subsequent lateralisation of motor symptoms are distinctive features of Parkinson's disease compared to other forms of neurodegenerative or symptomatic parkinsonism. Even 200 years after the first description of the disease, the underlying causes for this striking clinicopathological feature are not yet fully understood. There is increasing evidence that lateralisation of disease is due to a complex interplay of hereditary and environmental factors that are reflected not only in the concept of dominant hemispheres and handedness but also in specific susceptibilities of neuronal subpopulations within the substantia nigra. As a consequence, not only the obvious lateralisation of motor symptoms occurs but also patterns of associated non-motor signs are defined, which include cognitive functions, sleep behaviour or olfaction. Better understanding of the mechanisms contributing to lateralisation of neurodegeneration and the resulting patterns of clinical phenotypes based on bilateral post-mortem brain analyses and clinical studies focusing on right/left hemispheric symptom origin will help to develop more targeted therapeutic approaches, taking into account subtypes of PD as a heterogeneous disorder.

[Current aspects of therapy conversion for multiple sclerosis]. / Aktuelles zur Therapieumstellung bei Multipler Sklerose.

In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.