Editorial: Metal-related neurological disorders: several new genes and better understanding. Preface

It is a captivating era to be working in neurology as recent years have engendered fascinating developments. To illustrate, we have put together a special edition dedicated to metal-related neurological disease. Different topics are covered including disorders related to neural accumulation of iron (i.e., syndromes of neurodegeneration with brain iron accumulation), manganese, copper, or calcium. In recent years, neurogenetic workup has provided valuable insights with numerous genes characterized and yet more new genes on the threshold. The increasing number of genetic tests that have become commercially available (most recently as gene panels at more and more affordable costs) is of great clinical relevance and calls for an informed selection of the right test(s). Furthermore, new genetic approaches confirm that heritable factors underlie a larger proportion of patients than anticipated and genetic mutations should thus also be suspected in patients with a negative family history (i.e., due to de novo mutations). In parallel, there have been pathological advances, which can be correlated to molecular findings and which may challenge some of the previously held concepts for, for example, the presence of Lewy body pathology, and this link makes it clear that study of rare disorders may have ramifications and help in the understanding of more common conditions like Parkinson's disease (PD). Improved imaging techniques with higher resolution and new sequences with increased sensitivity to certain tissues lead to radiological-phenotypic-genotypic correlations. All these findings shed light on the complexity of metal-related diseases. However, their broader pathophysiology remains ill-understood. Mitochondrial dysfunction, abnormal lysosomal metabolism, and altered lipid pathways are all suspected to play a role in these Mendelian disorders; however, we have only just begun to unravel the complex puzzle of genes, the environment, and the aging brain. Improved scientific understanding will in the future hopefully provide the basis for the development of specific and even curative therapies for our patients.