@article{RauschenbergerKnorrPisanietal.2021,
  author    = {Rauschenberger, Lisa and Knorr, Susanne and Pisani, Antonio and Hallett, Mark and Volkmann, Jens and Ip, Chi Wang},
  title     = {Second hit hypothesis in dystonia: Dysfunctional cross talk between neuroplasticity and environment?},
  series = {Neurobiology of Disease},
  volume    = {159},
  journal   = {Neurobiology of Disease},
  doi       = {10.1016/j.nbd.2021.105511},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265028},
  year      = {2021},
  abstract  = {One of the great mysteries in dystonia pathophysiology is the role of environmental factors in disease onset and development. Progress has been made in defining the genetic components of dystonic syndromes, still the mechanisms behind the discrepant relationship between dystonic genotype and phenotype remain largely unclear. Within this review, the preclinical and clinical evidence for environmental stressors as disease modifiers in dystonia pathogenesis are summarized and critically evaluated. The potential role of extragenetic factors is discussed in monogenic as well as adult-onset isolated dystonia. The available clinical evidence for a "second hit" is analyzed in light of the reduced penetrance of monogenic dystonic syndromes and put into context with evidence from animal and cellular models. The contradictory studies on adult-onset dystonia are discussed in detail and backed up by evidence from animal models. Taken together, there is clear evidence of a gene-environment interaction in dystonia, which should be considered in the continued quest to unravel dystonia pathophysiology.},
  language  = {en}
}
@article{Gonzalez‐EscamillaMuthuramanReichetal.2019,
  author    = {Gonzalez-Escamilla, Gabriel and Muthuraman, Muthuraman and Reich, Martin M. and Koirala, Nabin and Riedel, Christian and Glaser, Martin and Lange, Florian and Deuschl, G{\"u}nther and Volkmann, Jens and Groppa, Sergiu},
  title     = {Cortical network fingerprints predict deep brain stimulation outcome in dystonia},
  series = {Movement Disorders},
  volume    = {34},
  journal   = {Movement Disorders},
  number    = {10},
  doi       = {10.1002/mds.27808},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213532},
  pages     = {1536 -- 1545},
  year      = {2019},
  abstract  = {Background Deep brain stimulation (DBS) is an effective evidence-based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigated whether patients optimally responding to DBS present distinct brain network organization and structural patterns. Methods From a German multicenter cohort of 82 dystonia patients with segmental and generalized dystonia who received DBS implantation in the globus pallidus internus, we classified patients based on the clinical response 3 years after DBS. Patients were assigned to the superior-outcome group or moderate-outcome group, depending on whether they had above or below 70\% motor improvement, respectively. Fifty-one patients met MRI-quality and treatment response requirements (mean age, 51.3 ± 13.2 years; 25 female) and were included in further analysis. From preoperative MRI we assessed cortical thickness and structural covariance, which were then fed into network analysis using graph theory. We designed a support vector machine to classify subjects for the clinical response based on individual gray-matter fingerprints. Results The moderate-outcome group showed cortical atrophy mainly in the sensorimotor and visuomotor areas and disturbed network topology in these regions. The structural integrity of the cortical mantle explained about 45\% of the DBS stimulation amplitude for optimal response in individual subjects. Classification analyses achieved up to 88\% of accuracy using individual gray-matter atrophy patterns to predict DBS outcomes. Conclusions The analysis of cortical integrity, informed by group-level network properties, could be developed into independent predictors to identify dystonia patients who benefit from DBS.},
  language  = {en}
}