Torsten Grehl

Alfried Krupp Hospital

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Thomas Meyer

Charité - Universitätsmedizin Berlin

Julian Großkreutz

University of Lübeck

Susanne Petri

Medizinische Hochschule Hannover

Albert C. Ludolph

German Center for Neurodegenerative Diseases

Patrick Weydt

University of Bonn

Jochen H. Weishaupt

Heidelberg University

Ute Weyen

BG University Hospital Bergmannsheil Bochum

Matthias Boentert

University Hospital Münster

Dagmar Kettemann

Humboldt-Universität zu Berlin

Jan Christoph Koch

Universitätsmedizin Göttingen

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Klinik und Poliklinik für Neurologie

German Center for Neurodegenerative Diseases

Universität Ulm

Ruhr University Bochum

Charité - Universitätsmedizin Berlin

University of Cologne

Heidelberg University

Ludwig-Maximilians-Universität München

University Hospital Ulm

University Hospital Cologne

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Amyotrophe Lateralsklerose und andere Motoneuronerkrankungen

Elisa Aust Matthias Boentert Dávid Brenner Torsten Grehl Julian Großkreutz

10.17433/978-3-17-039167-3

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Citations (1)

Ataxin-2 intermediate-length polyglutamine expansions in European ALS patients

Human Molecular Genetics (2011)

T. Lee Leslie A. Lange Caroline Ingre Markus Weber Torsten Grehl

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease primarily affecting motor neurons. We recently identified intermediate-length polyglutamine (polyQ) expansions (27-33 Qs) in ataxin 2 as a genetic risk factor for sporadic ALS in North American ALS patients. To extend these findings, we assessed the ataxin 2 polyQ repeat length in 1294 European ALS patients and 679 matched healthy controls. We observed a significant association between polyQ expansions and ALS (>30 Qs; P= 6.2 × 10(-3)). Thus, intermediate-length ataxin 2 polyQ repeat expansions are associated with increased risk for ALS also in the European cohort. The specific polyQ length cutoff, however, appears to vary between different populations, with longer repeat lengths showing a clear association. Our findings support the hypothesis that ataxin 2 plays an important role in predisposing to ALS and that polyQ expansions in ataxin 2 are a significant risk factor for the disease.

10.1093/hmg/ddr045

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Citations (142)

Begutachtung in der Neurologie

Bernhard Widder Peter W. Gaidzik Heinz-Harro Rauschelbach Kurt-Alphons Jochheim Clemens Cording

Dem klinisch tatigen Arzt erscheinen rechtliche Fragen fachfremd und werden haufig auch nicht wahrend des Studiums oder in der Weiterbildung vermittelt. Nicht selten betrifft dies sogar die durch die eigene Tatigkeit begrundete Arzthaftung, deren wichtigste Fallstricke allenfalls marginal bekannt sind. Seit Wegfall der Forderung nach einer Mindestzahl selbst erstatteter Gutachten in der Weiterbildungsordnung besteht bei jungeren Arzten oft auch nur noch ein geringes Interesse an der Durchfuhrung von Begutachtungen, obwohl diese – zumindest in einigen Rechtsgebieten – durchaus adaquat honoriert werden. Versicherte haben jedoch nicht nur Anspruch auf eine sachgerechte arztliche Behandlung, sondern im Krankheits- oder Schadensfall gleichermasen auch auf eine kompetente arztliche Begutachtung. Daruber hinaus liegen die volkswirtschaftlichen Kosten fur – haufig durch Gutachten induzierte – Renten- und Entschadigungszahlungen in derselben Grosenordnung wie die der Krankenversicherung. Ein wesentlicher Grund fur das geringe Interesse an Begutachtungen mag darin liegen, dass viele Arzte sich im Bereich rechtlicher Fragen ausgesprochen unsicher fuhlen und dann lieber die Hande davon lassen, um nicht in eine der zahlreichen „Fallgruben“ zu sturzen. Der nachfolgende Beitrag versucht ein Grundgerust fur den Umgang mit Begutachtungen zu vermitteln.

10.1055/b-002-19490

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A prospective study to evaluate the impact of³¹P‐MRS to determinate mitochondrial dysfunction in skeletal muscle of ALS patients

Amyotrophic Lateral Sclerosis (2007)

Torsten Grehl Stephan Fischer Klaus Müller J.-P. Malin Jochen Zange

Impaired mitochondrial energy production probably plays a role in motor neuron death in amyotrophic lateral sclerosis (ALS) and has been found not only in motor neurons but also in skeletal muscle of patients with ALS. 31P magnetic resonance spectroscopy (31P‐MRS) has the potential to reflect the energy metabolism of skeletal muscle in vivo. We sought to determine whether an altered mitochondrial energy metabolism of the muscle cell in patients with SALS can be detected by 31P‐MRS, and to this end we recorded 31P‐MR spectra of the gastrocnemius muscle of patients with ALS under a standardized isometric muscle exercise protocol. In a prospective setting we compared ten patients with sporadic ALS and 38 age‐matched controls. The patients were characterized by a disease duration of approximate 18 months and classified as having probable to definite ALS by means of the revised El Escorial criteria. The time constant of oxidative PCr recovery after aerobic (τ1) and ischaemic muscle contraction (τ2) was used to determine the capacity of mitochondrial ATP formation. We found that mitochondrial impairment in skeletal muscle of patients with ALS could not be confirmed by 31P‐MRS and therefore cannot be used as a surrogate factor of the disease.

10.1080/17482960600765065

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Self-Assessment of amyotrophic lateral sclerosis functional rating scale on the patients smartphone proves to be non-inferior to clinic data capture

medRxiv (Cold Spring Harbor Laboratory) (2024)

Laura Steinfurth Torsten Grehl Ute Weyen Dagmar Kettemann Robert Steinbach

Objective: To investigate self assessment of the amyotrophic lateral sclerosis functional rating scale revised (ALSFRSR) using the patients smartphone and to analyze noninferiority to clinic assessment. Methods: In an observational study, ALSFRSR data being remotely collected on a mobile application (AppALSFRSR) were compared to ALSFRSR captured during clinic visits (clinicALSFRSR). ALS progression rate (ALSPR) as calculated by the monthly decline of ALSFRSR, and its intrasubject variability (ALSPRISV) between ratings were used to compare both cohorts. To investigate noninferiority of AppALSFRSR data, a noninferiority margin was determined. Results: 691 ALS patients using the ALSApp, and 1895 patients with clinic assessments were included. Clinical characteristics for the AppALSFRSR and clinicALSFRSR cohorts were as follows: Mean age 60.45 (SD 10.43) and 63.69 (SD 11.30) years (p<0.001), disease duration 38.7 (SD 37.68) and 56.75 (SD 54.34) months (p<0.001) and ALSPR 0.72 and 0.59 (p<0.001), respectively. A paired sample analysis of ALSPRISV was applicable for 398 patients with clinic as well as app assessments and did not show a significant difference (IQR 0.12 [CI 0.11, 0.14] vs 0.12 [CI 0.11, 0.14], p=0.24; Cohens d =0.06). CI of IQR for AppALSFRSR was below the predefined noninferiority margin of 0.15 IQR, demonstrating noninferiority. Conclusions: Patients using a mobile application for remote digital self assessment of the ALSFRSR revealed younger age, earlier disease course and faster ALS progression. The finding of noninferiority of AppALSFRSR assessments underscores, that data collection using the ALSApp on the patients smartphone can serve as additional source of ALSFRSR in ALS research and clinical practice.

10.1101/2024.12.03.24318381

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31p-NMR spectroscopy in muscle phosphofructokinase

Torsten Grehl Matthias Vorgerd Martin Tegenthoff J.-P. Malin Jochen Zange

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Use and subjective experience of the impact of motor-assisted movement exercisers in people with amyotrophic lateral sclerosis: a multicenter observational study

Scientific Reports (2022)

André Maier Marcel Gaudlitz Torsten Grehl Ute Weyen Robert Steinbach

Abstract Motor-assisted movement exercisers (MME) are devices that assist with physical therapy in domestic settings for people living with ALS. This observational cross-sectional study assesses the subjective experience of the therapy and analyzes users' likelihood of recommending treatment with MME. The study was implemented in ten ALS centers between February 2019 and October 2020, and was coordinated by the research platform Ambulanzpartner. Participants assessed symptom severity, documented frequency of MME use and rated the subjective benefits of therapy on a numerical scale (NRS, 0 to 10 points, with 10 being the highest). The Net Promotor Score (NPS) determined the likelihood of a participant recommending MME. Data for 144 participants were analyzed. Weekly MME use ranged from 1 to 4 times for 41% of participants, 5 to 7 times for 42%, and over 7 times for 17%. Particularly positive results were recorded in the following domains: amplification of a sense of achievement (67%), diminution of the feeling of having rigid limbs (63%), diminution of the feeling of being immobile (61%), improvement of general wellbeing (55%) and reduction of muscle stiffness (52%). Participants with more pronounced self-reported muscle weakness were more likely to note a beneficial effect on the preservation and improvement of muscle strength during MME treatment (p < 0.05). Overall, the NPS for MME was high (+ 61). High-frequency MME-assisted treatment (defined as a minimum of five sessions a week) was administered in the majority of participants (59%) in addition to physical therapy. Most patients reported having achieved their individual therapeutic objectives, as evidenced by a high level of satisfaction with MME therapy. The results bolster the justification for extended MME treatment as part of a holistic approach to ALS care.

Muscle weakness

10.1038/s41598-022-13761-6

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Citations (7)

Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: a prospective observational study

Journal of Neurology (2015)

Johannes Dorst Luc Dupuis Susanne Petri Katja Kollewe Susanne Abdulla

Percutaneous endoscopic gastrostomy

Neuroradiology

Interventional radiology

10.1007/s00415-015-7646-2

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Citations (95)

Diagnostic and prognostic significance of neurofilament light chain NF-L, but not progranulin and S100B, in the course of amyotrophic lateral sclerosis: Data from the German MND-net

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration (2016)

Petra Steinacker André Huss Benjamin Mayer Torsten Grehl Julian Großkreutz

There is a need for diagnostic, prognostic, and monitoring blood biomarkers for ALS. We aimed to analyse and compare proposed candidate markers for disease progression in the course of ALS. Blood samples were taken from 125 ALS patients, including nine patients with C9orf72 or SOD1 mutation, at regular intervals of six months. ALS patients were characterized by the ALS functional rating scale (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). We quantified neurofilament light chain (NF-L), S100B, and progranulin (PGRN) and analysed it in relation to disease progression. Results showed that, at baseline, serum concentrations of NF-L but not PGRN or S100B discriminated significantly between ALS and controls. Within 24 months follow-up the marker concentrations remained stable. Baseline serum NF-L levels correlated with survival time, which was confirmed in subgroups with fast, intermediate, and slow disease progression and there was a weak association with disease duration. For S100B and PGRN we found an association with ALSFRS-R score changes and a trend for decreased levels in the fast progressor subgroup. In conclusion, serum NF-L in any ALS disease stage is a promising marker to support diagnosis and predict outcome, while serum PGRN and S100B are only of minor prognostic value.

C9ORF72

Neurofilament

10.1080/21678421.2016.1241279

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Citations (77)

31P-NMR spectroscopy in muscle phosphofructokinase deficiency

Neuromuscular Disorders (1997)

Torsten Grehl Matthias Vorgerd Martin Tegenthoff J.-P. Malin Jochen Zange

10.1016/s0960-8966(97)87253-7

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