31870
2022
eng
1545
1549
5
29
article
1
--
--
--
Current-dependent ocular tilt reaction in deep brain stimulation of the subthalamic nucleus: Evidence for an incerto-interstitial pathway?
Background and purpose
The aim was to characterize a combined vestibular, ocular motor and postural syndrome induced by deep brain stimulation (DBS) of the subthalamic nucleus in a patient with Parkinson's disease.
Methods
In a systematic DBS programming session, eye, head and trunk position in roll and pitch plane were documented as a function of stimulation amplitude and field direction. Repeat ocular coherence tomography was used to estimate ocular torsion. The interstitial nucleus of Cajal (INC), zona incerta (ZI) and ascending vestibular fibre tracts were segmented on magnetic resonance imaging using both individual and normative structural connectomic data. Thresholded symptom-associated volumes of tissue activated (VTA) were calculated based on documented stimulation parameters.
Results
Ipsilateral ocular tilt reaction and body lateropulsion as well as contralateral torsional nystagmus were elicited by the right electrode in a current-dependent manner and subsided after DBS deactivation. With increasing currents, binocular tonic upgaze and body retropulsion were observed. Symptoms were consistent with an irritative effect on the INC. Symptom-associated VTA was found to overlap with the dorsal ZI and the ipsilateral vestibulothalamic tract, while lying rather distant to the INC proper. A ZI-to-INC ‘incerto-interstitial’ tract with contact to the medial-uppermost portion of the VTA could be traced.
Conclusion
Unilateral stimulation of INC-related circuitry induces an ipsilateral vestibular, ocular motor and postural roll-plane syndrome, which converts into a pitch-plane syndrome when functional activation expands bilaterally. In this case, tractography points to an incerto-interstitial pathway, a tract previously only characterized in non-human primates. Directional current steering proved useful in managing this rare side effect.
European Journal of Neurology
10.1111/ene.15257
urn:nbn:de:bvb:20-opus-318700
@articleFriedrich.2022, author = Friedrich, Maximilian U. and Eldebakey, Hazem and Roothans, Jonas and Capetian, Philipp and Zwergal, Andreas and Volkmann, Jens and Reich, Martin, year = 2022, title = Current-dependent ocular tilt reaction in deep brain stimulation of the subthalamic nucleus: Evidence for an incerto-interstitial pathway?, pages = 1545–1549, volume = 29, number = 5, journal = European journal of neurology, doi = 10.1111/ene.15257,
md5:5a778c459876b7fecd21c0ac626af14b
2023-06-06T13:49:46+00:00
/tmp/phpVQ0ftg
bibtex
647f397a4ec717.03211419
European Journal of Neurology 2022, 29(5):1545-1549. DOI: 10.1111/ene.15257
false
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Maximilian U. Friedrich
Hazem Eldebakey
Jonas Roothans
Philipp Capetian
Andreas Zwergal
Jens Volkmann
Martin Reich
eng
uncontrolled
deep brain stimulation
eng
uncontrolled
vestibular
eng
uncontrolled
movement disorders
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/31870/Friedrich_European.pdf
24963
2021
eng
12
article
1
--
2021-11-08
--
Reduced Programming Time and Strong Symptom Control Even in Chronic Course Through Imaging-Based DBS Programming
Objectives: Deep brain stimulation (DBS) programming is based on clinical response testing. Our clinical pilot trial assessed the feasibility of image-guided programing using software depicting the lead location in a patient-specific anatomical model.
Methods: Parkinson's disease patients with subthalamic nucleus-DBS were randomly assigned to standard clinical-based programming (CBP) or anatomical-based (imaging-guided) programming (ABP) in an 8-week crossover trial. Programming characteristics and clinical outcomes were evaluated.
Results: In 10 patients, both programs led to similar motor symptom control (MDS-UPDRS III) after 4 weeks (medicationOFF/stimulationON; CPB: 18.27 ± 9.23; ABP: 18.37 ± 6.66). Stimulation settings were not significantly different, apart from higher frequency in the baseline program than CBP (p = 0.01) or ABP (p = 0.003). Time spent in a program was not significantly different (CBP: 86.1 ± 29.82%, ABP: 88.6 ± 29.0%). Programing time was significantly shorter (p = 0.039) with ABP (19.78 ± 5.86 min) than CBP (45.22 ± 18.32).
Conclusion: Image-guided DBS programming in PD patients drastically reduces programming time without compromising symptom control and patient satisfaction in this small feasibility trial.
Frontiers in Neurology
1664-2295
10.3389/fneur.2021.785529
urn:nbn:de:bvb:20-opus-249634
2021-11-24T13:12:08+00:00
sword
swordwue
attachment; filename=deposit.zip
ef3c7332931edc9522d14e6585a6e88b
Frontiers in Neurology (2021) 12:785529. doi: 10.3389/fneur.2021.785529
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Florian Lange
Frank Steigerwald
Tobias Malzacher
Gregor Alexander Brandt
Thorsten Michael Odorfer
Jonas Roothans
Martin M. Reich
Patrick Fricke
Jens Volkmann
Cordula Matthies
Philipp D. Capetian
eng
uncontrolled
directional deep brain stimulation
eng
uncontrolled
image-guided programming
eng
uncontrolled
subthalamic nucleus
eng
uncontrolled
chronic stimulation
eng
uncontrolled
randomized controlled double-blind study
eng
uncontrolled
Parkinson's disease
Medizin und Gesundheit
open_access
Neurochirurgische Klinik und Poliklinik
Neurologische Klinik und Poliklinik
Import
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24963/fneur-12-785529.pdf
23605
2020
eng
5
21
article
1
2021-04-28
--
--
Visualizing the synaptic and cellular ultrastructure in neurons differentiated from human induced neural stem cells - an optimized protocol
The size of the synaptic subcomponents falls below the limits of visible light microscopy. Despite new developments in advanced microscopy techniques, the resolution of transmission electron microscopy (TEM) remains unsurpassed. The requirements of tissue preservation are very high, and human post mortem material often does not offer adequate quality. However, new reprogramming techniques that generate human neurons in vitro provide samples that can easily fulfill these requirements. The objective of this study was to identify the culture technique with the best ultrastructural preservation in combination with the best embedding and contrasting technique for visualizing neuronal elements. Two induced neural stem cell lines derived from healthy control subjects underwent differentiation either adherent on glass coverslips, embedded in a droplet of highly concentrated Matrigel, or as a compact neurosphere. Afterward, they were fixed using a combination of glutaraldehyde (GA) and paraformaldehyde (PFA) followed by three approaches (standard stain, Ruthenium red stain, high contrast en-bloc stain) using different combinations of membrane enhancing and contrasting steps before ultrathin sectioning and imaging by TEM. The compact free-floating neurospheres exhibited the best ultrastructural preservation. High-contrast en-bloc stain offered particularly sharp staining of membrane structures and the highest quality visualization of neuronal structures. In conclusion, compact neurospheres growing under free-floating conditions in combination with a high contrast en-bloc staining protocol, offer the optimal preservation and contrast with a particular focus on visualizing membrane structures as required for analyzing synaptic structures.
International Journal of Molecular Sciences
10.3390/ijms21051708
urn:nbn:de:bvb:20-opus-236053
1422-0067
publish
International Journal of Molecular Sciences (2020) 21:5, 1708. https://doi.org/10.3390/ijms21051708
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Philipp Capetian
Lorenz Müller
Jens Volkmann
Manfred Heckmann
Süleyman Ergün
Nicole Wagner
eng
uncontrolled
transmission electron microscopy
eng
uncontrolled
human neurons
eng
uncontrolled
induced neural stem cells
eng
uncontrolled
synapse
eng
uncontrolled
synaptic vesicles
eng
uncontrolled
high contrast
Medizin und Gesundheit
open_access
Institut für Anatomie und Zellbiologie
Physiologisches Institut
Neurologische Klinik und Poliklinik
Förderzeitraum 2020
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23605/ijms-21-01708-v2.pdf
24460
2021
eng
9
article
1
--
2021-08-18
--
Ventral Telencephalic Patterning Protocols for Induced Pluripotent Stem Cells
The differentiation of human induced pluripotent stem cells (hiPSCs) into specific cell types for disease modeling and restorative therapies is a key research agenda and offers the possibility to obtain patient-specific cells of interest for a wide range of diseases. Basal forebrain cholinergic neurons (BFCNs) play a particular role in the pathophysiology of Alzheimer’s dementia and isolated dystonias. In this work, various directed differentiation protocols based on monolayer neural induction were tested for their effectiveness in promoting a ventral telencephalic phenotype and generating BFCN. Ventralizing factors [i.e., purmorphamine and Sonic hedgehog (SHH)] were applied at different time points, time intervals, and concentrations. In addition, caudal identity was prevented by the use of a small molecule XAV-939 that inhibits the Wnt-pathway. After patterning, gene expression profiles were analyzed by quantitative PCR (qPCR). Rostro-ventral patterning is most effective when initiated simultaneously with neural induction. The most promising combination of patterning factors was 0.5 μM of purmorphamine and 1 μM of XAV-939, which induces the highest expression of transcription factors specific for the medial ganglionic eminence, the source of GABAergic inter- and cholinergic neurons in the telencephalon. Upon maturation of cells, the immune phenotype, as well as electrophysiological properties were investigated showing the presence of marker proteins specific for BFCN (choline acetyltransferase, ISL1, p75, and NKX2.1) and GABAergic neurons. Moreover, a considerable fraction of measured cells displayed mature electrophysiological properties. Synaptic boutons containing the vesicular acetylcholine transporter (VACHT) could be observed in the vicinity of the cells. This work will help to generate basal forebrain interneurons from hiPSCs, providing a promising platform for modeling neurological diseases, such as Alzheimer’s disease or Dystonia.
Frontiers in Cell and Developmental Biology
2296-634X
10.3389/fcell.2021.716249
urn:nbn:de:bvb:20-opus-244607
2021-09-13T09:03:06+00:00
sword
swordwue
attachment; filename=deposit.zip
1e4e61bd5dc2e01b0bd0b1953ba994e7
Frontiers in Cell and Developmental Biology (2021) 9:716249. doi: 10.3389/fcell.2021.716249
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Victor Krajka
Maximilian Naujock
Martje G. Pauly
Felix Stengel
Britta Meier
Nancy Stanslowsky
Christine Klein
Philip Seibler
Florian Wegner
Philipp Capetian
eng
uncontrolled
induced pluripotent stem cells
eng
uncontrolled
medial ganglionic eminence
eng
uncontrolled
Sonic hedgehog
eng
uncontrolled
XAV-939
eng
uncontrolled
purmorphamine
eng
uncontrolled
basal forebrain cholinergic neurons
eng
uncontrolled
GABAergic neurons
eng
uncontrolled
electrophysiology
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Import
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24460/fcell-09-716249.pdf
24117
2020
eng
3993–4001
47
article
1
--
--
--
Impaired differentiation of human induced neural stem cells by TOR1A overexpression
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.
Molecular Biology Reports
10.25972/OPUS-24117
urn:nbn:de:bvb:20-opus-241177
https://doi.org/10.1007/s11033-020-05390-x
Molecular Biology Reports 47, 3993–4001 (2020). https://doi.org/10.1007/s11033-020-05390-x
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Felix Stengel
Franca Vulinovic
Britta Meier
Karen Grütz
Christine Klein
Philipp Capetian
eng
uncontrolled
dystonia
eng
uncontrolled
DYT1
eng
uncontrolled
torsinA
eng
uncontrolled
TOR1A
eng
uncontrolled
neuronal stem cells
eng
uncontrolled
neuronal differentiation
eng
uncontrolled
inducible expression
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24117/Stengel2020_Article_ImpairedDifferentiationOfHuman.pdf
23577
2021
eng
115-121
128
article
1
2021-04-26
--
--
Altered urinary tetrahydroisoquinoline derivatives in patients with Tourette syndrome: reflection of dopaminergic hyperactivity?
Tetrahydroisoquinolines (TIQs) such as salsolinol (SAL), norsalsolinol (NSAL) and their methylated derivatives N-methyl-norsalsolinol (NMNSAL) and N-methyl-salsolinol (NMSAL), modulate dopaminergic neurotransmission and metabolism in the central nervous system. Dopaminergic neurotransmission is thought to play an important role in the pathophysiology of chronic tic disorders, such as Tourette syndrome (TS). Therefore, the urinary concentrations of these TIQ derivatives were measured in patients with TS and patients with comorbid attention-deficit/hyperactivity disorder (TS + ADHD) compared with controls. Seventeen patients with TS, 12 with TS and ADHD, and 19 age-matched healthy controls with no medication took part in this study. Free levels of NSAL, NMNSAL, SAL, and NMSAL in urine were measured by a two-phase chromatographic approach. Furthermore, individual TIQ concentrations in TS patients were used in receiver-operating characteristics (ROC) curve analysis to examine the diagnostic value. NSAL concentrations were elevated significantly in TS [434.67 ± 55.4 nmol/l (standard error of mean = S.E.M.), two-way ANOVA, p < 0.0001] and TS + ADHD patients [605.18 ± 170.21 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] compared with controls [107.02 ± 33.18 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] and NSAL levels in TS + ADHD patients were elevated significantly in comparison with TS patients (two-way ANOVA, p = 0.017). NSAL demonstrated an AUC of 0.93 ± 0.046 (S.E.M) the highest diagnostic value of all metabolites for the diagnosis of TS. Our results suggest a dopaminergic hyperactivity underlying the pathophysiology of TS and ADHD. In addition, NSAL concentrations in urine may be a potential diagnostic biomarker of TS.
Journal of Neural Transmission
0300-9564
10.1007/s00702-020-02289-6
urn:nbn:de:bvb:20-opus-235771
publish
Journal of Neural Transmission (2021) 128:115–120. https://doi.org/10.1007/s00702-020-02289-6
true
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Philipp Capetian
Veit Roessner
Caroline Korte
Susanne Walitza
Franz Riederer
Regina Taurines
Manfred Gerlach
Andreas Moser
eng
uncontrolled
Tourette syndrome
eng
uncontrolled
ADHD
eng
uncontrolled
tics
eng
uncontrolled
biomarkers
eng
uncontrolled
tetrahydroisoquinoline derivates
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23577/Capetian2021_Article_AlteredUrinaryTetrahydroisoqui.pdf
31349
2023
eng
4
10
article
1
--
2023-04-15
--
Pallidal recordings in chronically implanted dystonic patients: mitigation of tremor-related artifacts
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.
Bioengineering
2306-5354
10.3390/bioengineering10040476
urn:nbn:de:bvb:20-opus-313498
2023-05-05T09:22:07+00:00
sword
swordwue
attachment; filename=deposit.zip
b3172bf3121162ae3315b28c86045bed
Bioengineering (2023) 10:4, 476. https://doi.org/10.3390/bioengineering10040476
758985
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Jasmin Del Vecchio
Ibrahem Hanafi
Nicoló Gabriele Pozzi
Philipp Capetian
Ioannis U. Isaias
Stefan Haufe
Chiara Palmisano
eng
uncontrolled
dystonia
eng
uncontrolled
tremor
eng
uncontrolled
local field potentials
eng
uncontrolled
globus pallidus
eng
uncontrolled
deep brain stimulation
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
OpenAIRE
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/31349/bioengineering-10-00476-v2.pdf