Faculty of Medicine
Faculty of Medicine
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[FG] Clinical Biomechanics

Projects & Collaborations

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Dynamic foot function in patients with Charcot Marie Tooth disease

Research Project  | 5 Project Members

Charcot-Marie-Tooth disease (CMT) stands as one of the most prevalent hereditary neurological disorders, also recognized as hereditary motor and sensory neuropathy (HMSN) [1]. It ranks as the most common inherited neuropathy. CMT displays genetic diversity, involving over 80 mutated genes with varying inheritance patterns [2]. 

The majority of CMT cases fall into the CMT1 group, characterized by a demyelinating pattern of nerve damage. Within this group, CMT1A comprises 70% of all CMT patients and is linked with a defect on chromosome 17 that affects the peripheral myelin protein. Conversely, CMT2 cases exhibit an axonal pattern of nerve damage [3]. 

Individuals with CMT typically experience progressive muscle atrophy and weakness, leading to foot deformities and less frequently, hand deformities. The progression of deformities varies based on genetic and phenotypic factors. The disease often manifests as a multiplanar foot deformity, with cavovarus being the most observed. This deformity entails hindfoot varus, a high arch (cavus), downward flexion of the first metatarsal, a forefoot that's pulled inward (adducted), and claw toes. It arises from an imbalance in muscle strength, where the peroneus longus muscle may be relatively strong compared to a weakened anterior tibial muscle, or where the posterior tibial muscle is strong while the peroneus brevis muscle is weak [4, 5]. 

Patients with cavovarus deformity experience varying degrees of sensory loss, muscle weakness, painful foot calluses, abnormal gait, and ankle instability [3-6]. Despite ongoing research, the full understanding of these deformities remains elusive, leading to a variety of treatment recommendations. Therefore, the aim of this project is, to investigate and characterize functional gait parameters in CMT patients to improve therapeutic management. 

To develop a sufficient therapeutic program (such as foot surgery and orthotics management), biomechanical knowledge on 1) the deviations from healthy function and 2) how the foot deformities influence dynamic function, are necessary.

1. Lisak RP., D.D.T., WILLIAM M. CARROLL, ROONGROJ BHIDAYASIRI, International Neurology – A Clinical Approach, ed. D.D.T. Lisak RP., WILLIAM M. CARROLL, ROONGROJ BHIDAYASIRI. 2009: Blackwell Publishing Ltd. 

2. Timmerman, V., A.V. Strickland, and S. Zuchner, Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success. Genes (Basel), 2014. 5(1): p. 13-32. 

3. Newman, C.J., et al., The characteristics of gait in Charcot-Marie-Tooth disease types I and II. Gait Posture, 2007. 26(1): p. 120-7. 

4. Mann, R.A. and J. Missirian, Pathophysiology of Charcot-Marie-Tooth disease. Clin Orthop Relat Res, 1988(234): p. 221-8. 

5. Beals, T.C. and F. Nickisch, Charcot-Marie-Tooth disease and the cavovarus foot. Foot Ankle Clin, 2008. 13(2): p. 259-74, vi-vii. 



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Patient-specific musculoskeletal models to predict surgical outcome

Research Project  | 3 Project Members

Instrumented clinical gait analysis is used routinely to inform decision-making in neuro-orthopaedics. In addition to gait analysis, musculoskeletal modeling may become a powerful and non-invasive tool to guide clinical management and predict treatment outcomes. However, musculoskeletal modeling needs to integrate patient-specific adaptations, and its outputs need to be validated on a larger scale before it may be used in standard clinical practice.

The goal of this project is to develop patient-specific gait simulations by means of an open-source musculoskeletal modeling software. Results will be validated against existing clinical data pre vs post a typical intervention in neuro-orthopaedics.

Personalized musculoskeletal models from 30 children who received botulinum toxin injection will be developed from gait analysis data obtained before the intervention. To predict patient's response, the botulinum toxin effect will be simulated by weakening the model muscle and running a forward dynamic simulation. I will compare the outcome against existent data post-injection and analyze how induced muscle weakness alters the gait of children with cerebral palsy, providing validation for this specific musculoskeletal modeling application and overall confidence in our framework reliability.


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CADENCE - Clinical Biomechanics and Ergonomics Engineering Equipment

Research Project  | 5 Project Members

In December 2021, the new research unit ‘Clinical Biomechanics and Ergonomics Engineering’ (CADENCE) was formed at Department of Biomedical Engineering (DBE) at the University of Basel (https://dbe.unibas.ch/en/research/biomechanics-and-biomaterials/cadence/) comprising the research groups ‘Functional Biomechanics’, ‘Robot-assisted Theragnostics’, ‘Paediatric Orthopaedic Biomechanics and Musculoskeletal Modelling’, and ‘Spine Biomechanics’. CADENCE facilitates innovative and groundbreaking interdisciplinary research in biomedical engineering and biomechanics and serves as teaching facility for courses on diagnostic and therapeutic technologies within the new Master of Science program and the PhD programs at the DBE. The R`Equip grant supports CADENCE in the purchase of a range of state-of-the-art sensor technologies and the world’s first 3D gait rehabilitation robot ‘The FLOAT’. This investment is critical for the unique and internationally leading role of the research groups in the research and innovation ecosystem in the Basel region.

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Stop tip-toeing around toe-walking: towards a better understanding and more effective treatment of toe-walkers with cerebral palsy

Research Project  | 8 Project Members

Background and Rationale: Walking is the most common and necessary form of movement for humans, as it ensures active participation in activities of daily life. In the initial stages of learning to walk, gait is rather unstable as well as variable. During this initial phase, children need to successfully perform the entire gait cycle that involves touch-down (characteristic heel-strike where the ankle is flexed), lift-off and swing phases. The characteristic heel-strike is critical to walking both effectively (stable) and efficiently (energy). Children that suffer from neuro-developmental disorders (e.g. cerebral palsy, CP) are often not able to heel-strike, they tend to keep walking with a forefoot or flatfoot pattern (i.e. toe-walking). Children that toe-walk often show poorer levels of static and dynamic stability, leading to a lower quality of life compared to typically developing children (TD). Current research suggests multifactorial adaptations in central and/or peripheral nervous as well as the musculoskeletal system contribute to and result from toe-walking. Current treatment mainly focuses on physically restoring the capability to heel-strike, however, adherence to walking with heel-strike is poor. From clinical experience, we hypothesize psychological factors (primarily fear-of-falling) as well as inadequate reflex control might contribute to toe-walking behavior. Currently, the interplay between the nervous-, musculoskeletal-, and psychological systems and their impact on resulting walking patterns are poorly understood. In order to sustain effective gait by means of effective interventions, it is therefore critical to understand the interplay among the mechanisms that underpin toe-walking adaptation. Overall Objectives & Specific Aims: The purpose of this study is to explore the interplay among nervous-, musculoskeletal-, and psychological systems and how they impact toe-walking behavior, and vice versa. Here, we will determine the effect of psychological factors (via the use of a custom-designed virtual reality environment) on static vs. dynamic stability, motor control and coordination (indirect assessment of central nervous system function), as well as reflex control (Hoffmann-reflex, H-reflex, performance of peripheral nervous system). In addition, we will also investigate the effect of restoring heel striking in toe-walkers based on the indices as mentioned above. Expected Results: It is expected that toe-walkers will show poorer stability during standing and walking, have a reduced H-reflex amplitude, reduced number of muscle synergies as well as increased fear-of-falling compared to TD. With the use of a custom-made virtual reality (VR) environment, the fear-of-falling in children will be increased. VR induced fear-of-falling will lead to poorer stability during standing and walking tasks in TD; in toe-walkers such reactions are present already without VR but worsen during VR conditions. By restoring (via the use of orthoses) heel-strike in toe-walkers stability during standing and walking tasks will be improved, number of muscle synergies will be increased, fear-of-falling will be reduced, and performance on VR induced fear-of-falling will be improved. Impact: Although development of heel-strike behavior takes place early in life, not all children demonstrate this feature during walking in daily life. Lack of heel-strike behavior is less efficient and leads to poorer quality of life. Management strategies to restore this critical feature of walking, have failed primarily due to the fact that although the capability might be restored, the adherence to walking with heel-strike is poor. By focusing on understanding the interplay between nervous-, musculoskeletal-, and psychological factors that might predispose individuals to toe-walking, we will provide solutions to design effective treatment strategies in the future.

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Surgical safety and effectiveness in orthopedics: Swiss-wide multicenter evaluation and prediction of core outcomes in arthroscopic rotator cuff reconstruction

Research Project  | 2 Project Members

Valid clinical outcome data are essential to assess the safety and effectiveness of surgical interventions, to perform benchmarking activities and to foster a well-founded decision-making process in orthopedics. In the fields of arthroscopic rotator cuff repair (ARCR), the number of ARCR procedures and published studies has grown exponentially in the last decade, yet reporting standards differ dramatically. This is particularly notable concerning adverse events (AE) as in most fields of orthopedic surgery. In addition, published prognostic studies were methodologically poor, based on small datasets and explored only limited numbers of potentially influencing factors.A prospective multicenter clinical study of a large ARCR patient cohort will be implemented on a representative group of 17 Swiss and one German specialized clinics allowing for the evaluation of targeted core safety, clinical and patient-reported outcomes. The primary objective will be the development of prediction models for individual patients. The primary outcomes will be the patient-reported subjective assessment of shoulder function (Oxford Shoulder Score) and the occurrence of shoulder stiffness up to 12 months after primary repair surgery. Multiple prognostic factors will be investigated including patient baseline demographics, psychological, socioeconomic and clinical factors, rotator cuff integrity and concomitant local findings, operative and postoperative management factors. The secondary objectives are to evaluate the content and applicability of a consensus core set of AEs (CES) considering the patient's perspective, validate a severity classification for AEs, and quantify clinically-relevant ARCR outcomes up to 24 months postoperatively. Prognostic models will also be extended to all secondary outcomes.A sample size of 970 ARCR patients will be included; baseline patient demographics, history, shoulder status, magnetic resonance imaging based diagnosis and operative details will be recorded. Patient outcomes will be documented 6, 12 and 24 months after surgery. Clinical examinations at 6 and 12 months will include shoulder range of motion and strength (Constant Score), as well as the documentation of AEs. Tendon repair integrity status will be assessed by ultrasound examination at 12 months. Patient-reported outcome questionnaires at all follow-up time points will determine functional scores (Subjective Shoulder Value, Oxford Shoulder Score), anxiety and depression scores, working status, quality of life (EuroQol EQ-5D-5L), and AEs. All AEs will be documented according to the consensus CES and classified by their degree of severity; patients will rate the perceived severity and disturbance of experienced AEs. We will use the web-based REDCap data capture system for data management. Intensive central monitoring will be performed and investigator meetings will be coordinated during the study. The adapted AE severity classification will be validated. All data will be tabulated and prediction models will be developed using internationally supported methodology.This project will initiate the development of personalized risk predictions to support the surgical decision process in ARCR. The consensus CES may become an international reference for the reporting of complications in clinical studies and registers. The proposed study will foster the condition towards the development of a Swiss national ARCR register. Such a study and registry is an important step to increasing transparency in orthopedic surgery as requested by the federal strategy in healthcare "Health 2020". Methodological insights gained from this work will be easily transferable to similar initiatives in orthopedics.

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Influence of additional weight carrying on load-induced changes in glenohumeral translation in patients with rotator cuff tear - a translational approach

Research Project  | 3 Project Members

The shoulder is a unique joint: the primary stabilization by the rotator cuff muscles facilitates a large range of motion that is a prerequisite for many daily, occupational and recreational activities. Accordingly, injury to the rotator cuff greatly affects joint function and limits the patients' activities. Rotator cuff tears are a common shoulder injury that sometimes remain undiagnosed because of limited symptoms. However, altered shoulder biomechanics because of injury - even when only subtle - can lead to secondary damage and degeneration including tendinopathy or osteoarthritis. Because of the overlying soft tissue, measuring shoulder biomechanics is complex. Motion of the healthy shoulder primarily comprises rotation with very small to no translation because of stabilization through muscle activity and is affected by muscle cross sectional area (MCSA) and shoulder anatomy including the critical shoulder angle (CSA) and glenoid inclination (GI). Although often clinically observed, inconclusive changes in shoulder translation have been reported in patients with rotator cuff tear. However, to date it is unknown how additional handheld weight similar to situations during daily, occupational or recreational activities affects glenohumeral translation in patients with rotator cuff tear. Based on previous methods for assessing glenohumeral translation, we have developed an in vivo, simulation and ex vivo experimental framework for systematically modulating additional weight during a loading shoulder abduction test that we propose to employ in this study. This framework allows us to assess the dose-response relationship between additional weight and glenohumeral translation termed load-induced glenohumeral translation (liTr). We will address the following specific aims in in vivo, simulation and ex vivo experiments: understanding the biological variation in liTr; understanding the influence of disease pathology on liTr; understanding the potential compensation of rotator cuff tear by muscle activation and muscle size; and understanding the association of liTr and patient outcomes. Patients with rotator cuff tears and asymptomatic persons with similar age and sex distribution will be clinically assessed and complete a loading shoulder abduction test while collecting single plane fluoroscopy images. The same test will be repeated while 3-dimensional (3D) motion data and electromyographic data is collected. In the motion analysis test and in the fluoroscopy test, handheld weight will be applied. LiTr will be calculated as the slope of a regression of the negative distance of the glenohumeral centre of rotation (GHJC) to the acromion and studied in relation to patient's functional scores, MCSA, tear size and type, and the CSA and GI. Moreover, we will extent a previously developed shoulder simulator to integrate glenoid specimen, anterior and posterior aspects of the deltoid muscle and facilitate simulation of individual tendon rupture. Subsequently, we will use this shoulder simulator in simulation and ex vivo experiments to systematically study the effect of tear size and type, CSA and GI in sawbones and human cadaveric specimen. Finally, we will compare results of in vivo, simulation and ex vivo experiments and formulate specific recommendation for clinic and rehabilitation. This study can be considered as proof-of-concept of a potential diagnostic test (loading shoulder abduction test) for glenohumeral translation and will provide first evidence of a dose-response relationship between additional weight and glenohumeral translation. Moreover, the simulation and ex vivo experiments using a shoulder simulator allow the systematic investigation of mechanical compensation for injury to one or more rotator cuff muscles. The results of this study are relevant for diagnostics, treatment and rehabilitation planning in this population.

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Muscle Function in Dynamic MRI in Patients with Cerebral Palsy Before and After Botulinum Toxin Injection

Research Project  | 4 Project Members

Muscle contractures are amongst the most frequently treated problems in children with cerebral palsy. They occur due to the aberrant muscle use under the neurological disorder and further impede function and daily activities. Foot equinus is one of the most frequent conditions, and treatment with injection of botulinum toxin has become a standard. In this study the functional properties of muscles - before and after the injection of botulinum toxin - in cerebral palsy patients will be assessed with a novel technique for the investigation of muscle function by MRI, based on synchronous electrical muscle stimulation (EMS). This approach provides information about muscle fibre length and angulation also in the active muscle, as well as contraction velocity and muscle strength. These data will be correlated with muscle pathology from needle biopsies and with gait function recorded by gait analysis. Synchronous EMS-MRI and gait analysis including dynamic superficial electromyography (EMG) will be applied three times to the patients: a) Before botulinum toxin injection, b) 6 weeks after botulinum toxin injection, and c) 3 months after botulinum toxin injection. Before botulinum toxin injection a needle biopsy of the selected muscle will be obtained from all patients. Muscle tissue is altered in cerebral palsy, and the biopsy provides the necessary histological data for understanding a possible atypical function before and after botulinum toxin injection assessed with EMS-induced MRI. For data comparison twelve healthy volunteers will be recruited whose data will serve as a normal reference. The volunteers will only obtain synchronous EMS-MRI and gait analysis including dynamic superficial EMG once. As we have histology data of normal muscles, biopsies and botulinum toxin injections are not required in these normal volunteers.The data of synchronous EMS-MRI from this study will be clinically relevant for several reasons:It may offer a non-invasive technique to obtain information on muscle pathophysiology in patients with cerebral palsy. A better knowledge of the function of the abnormal muscles during gait is essential for the adaptation of the current treatment options (e.g. less surgical lengthenings). It will further help to compute data from gait analysis more accurately as the parameters modifying the computations can be set according to the pathologies.Further, the information about the effect of botulinum toxin may help to explain some of the failures of current treatment procedures. It will be especially important to know how much of a muscle is affected and how the remaining part reacts. As a consequence of the study adaptations of the drug application may be required.

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Adaptation of functional control mechanisms when walking on uneven surface in patients with spastic hemiplegic cerebral palsy

Research Project  | 1 Project Members

Patients with unilateral (hemiplegic) cerebral palsy (CP) often report difficulties when walking on uneven surfaces. Motor control impairment associated with CP not only restricts patients' daily activities but also their integration into the society. For instance, patients with unilateral CP need more time for completing daily tasks such as shopping because of their difficulties in walking stairs and steps. Moreover, children with CP have trouble keeping up with their healthy peers playing outdoors where the ground is uneven. Therefore, therapy in these patients should mainly focus on restoring and developing the abilities to accomplish more demanding real life situations. Identifying and objectively quantifying motor control deficits and movement deviations is a prerequisite for developing a patient specific and task orientated therapy concept. However, these deficits cannot be discovered by analysing walking in a controlled laboratory setting with flat ground as done in a routine clinical gait analysis. The patients need to be assessed in a more demanding environment, such as walking on uneven ground to reveal the full dimension of their motor control deficits. The purpose of this study is to determine differences in the functional control mechanisms when walking on uneven ground between children with and without hemiplegic CP. I will identify gait parameters describing differences in functional control adaptations to walking on uneven ground between children with and without hemiplegic CP and determine if patients with hemiplegic CP require more time to adapt to the uneven ground during the transition from flat to uneven ground. A fast adaptation to a different surface is critical for preventing falls and beneficial when walking outside a laboratory or building. Gait patterns of 20 children with hemiplegic CP and 20 age-matched normally developing children will be compared when walking on flat and uneven ground. Three-dimensional joint kinematics, centre of mass movements, spatio-temporal parameters and muscle activity patterns derived by an instrumented gait analysis will be analysed. This study is a critical first step towards developing a new protocol for clinical gait analysis that includes walking on uneven surface. The knowledge gained in this study will be used for proposing a therapy concept aiming at training patient specific movement patterns to facilitate adaptation to uneven ground.

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Developmental Engineering of Cartilage from Adult MSCs - Mimicking Differentiation of Limb Mesenchymal Progenitors

Research Project  | 3 Project Members

Verletzungsbedingte und degenerative skeletale Krankheiten, die derzeit meist chirurgisch behandelt werden, könnten auch mit funktionellen skeletalen Ersatzgeweben behandelt werden. Durch die Nutzung von genetischen Modellen der Maus und den Vergleich des Maustranskriptoms von mesenchymalen Vorläuferzellen der Gliedmassen (LMP) mit Maus- und humanen MSCs, wollen wir (i) die gemeinsame moleculare Signatur zwischen LMP und MSCs identifizieren, (ii) die Marker für die Selektion von MSCs mit robustem chondrogenem Potential definieren, und (iii) eine entwicklungsinspirierte Strategie zur Züchtung von Knorpeltemplates entwickeln. Dadurch wird könnte es möglich sein Subpopulationen mit definierten funktionellen Eigenschaften zu identifizieren und stabile Protokolle für die Gewebezüchtung zu etablieren.