@article{DelVecchioHanafiPozzietal.2023, author = {Del Vecchio, Jasmin and Hanafi, Ibrahem and Pozzi, Nicol{\´o} Gabriele and Capetian, Philipp and Isaias, Ioannis U. and Haufe, Stefan and Palmisano, Chiara}, title = {Pallidal recordings in chronically implanted dystonic patients: mitigation of tremor-related artifacts}, series = {Bioengineering}, volume = {10}, journal = {Bioengineering}, number = {4}, issn = {2306-5354}, doi = {10.3390/bioengineering10040476}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313498}, year = {2023}, abstract = {Low-frequency oscillatory patterns of pallidal local field potentials (LFPs) have been proposed as a physiomarker for dystonia and hold the promise for personalized adaptive deep brain stimulation. Head tremor, a low-frequency involuntary rhythmic movement typical of cervical dystonia, may cause movement artifacts in LFP signals, compromising the reliability of low-frequency oscillations as biomarkers for adaptive neurostimulation. We investigated chronic pallidal LFPs with the Percept\(^{TM}\) PC (Medtronic PLC) device in eight subjects with dystonia (five with head tremors). We applied a multiple regression approach to pallidal LFPs in patients with head tremors using kinematic information measured with an inertial measurement unit (IMU) and an electromyographic signal (EMG). With IMU regression, we found tremor contamination in all subjects, whereas EMG regression identified it in only three out of five. IMU regression was also superior to EMG regression in removing tremor-related artifacts and resulted in a significant power reduction, especially in the theta-alpha band. Pallido-muscular coherence was affected by a head tremor and disappeared after IMU regression. Our results show that the Percept PC can record low-frequency oscillations but also reveal spectral contamination due to movement artifacts. IMU regression can identify such artifact contamination and be a suitable tool for its removal.}, language = {en} } @article{SchreglmannBurkeBatlaetal.2022, author = {Schreglmann, Sebastian R. and Burke, Derek and Batla, Amit and Kresojevic, Nikola and Wood, Nicholas and Heales, Simon and Bhatia, Kailash P.}, title = {Cerebellar and Midbrain Lysosomal Enzyme Deficiency in Isolated Dystonia}, series = {Movement Disorders}, volume = {37}, journal = {Movement Disorders}, number = {4}, doi = {10.1002/mds.28937}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318743}, pages = {875 -- 877}, year = {2022}, language = {en} } @article{SchreglmannBhatia2022, author = {Schreglmann, Sebastian R. and Bhatia, Kailash P.}, title = {HOPS-Associated Neurological Disorders: Lysosomal Dysfunction as an Emerging Concept Underlying Dystonia}, series = {Movement Disorders Clinical Practice}, volume = {9}, journal = {Movement Disorders Clinical Practice}, number = {4}, doi = {10.1002/mdc3.13405}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318736}, pages = {452 -- 453}, year = {2022}, language = {en} } @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{StengelVulinovicMeieretal.2020, author = {Stengel, Felix and Vulinovic, Franca and Meier, Britta and Gr{\"u}tz, Karen and Klein, Christine and Capetian, Philipp}, title = {Impaired differentiation of human induced neural stem cells by TOR1A overexpression}, series = {Molecular Biology Reports}, volume = {47}, journal = {Molecular Biology Reports}, doi = {10.25972/OPUS-24117}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241177}, pages = {3993-4001}, year = {2020}, abstract = {DYT-TOR1A is the most common inherited dystonia caused by a three nucleotide (GAG) deletion (dE) in the TOR1A gene. Death early after birth and cortical anomalies of the full knockout in rodents underscore its developmental importance. We therefore explored the timed effects of TOR1A-wt and TOR1A-dE during differentiation in a human neural in vitro model. We used lentiviral tet-ON expression of TOR1A-wt and -dE in induced neural stem cells derived from healthy donors. Overexpression was induced during proliferation of neural precursors, during differentiation and after differentiation into mature neurons. Overexpression of both wildtype and mutated protein had no effect on the viability and cell number of neural precursors as well as mature neurons when initiated before or after differentiation. However, if induced during differentiation, overexpression of TOR1A-wt and -dE led to a pronounced reduction of mature neurons in a dose dependent manner. Our data underscores the importance of physiological expression levels of TOR1A as crucial for proper neuronal differentiation. We did not find evidence for a specific impact of the mutated TOR1A on neuronal maturation.}, 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} }