PD Dr. Morgan Sangeux

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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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.

Cerebral palsy is the first cause of disability with a prevalence of about 2.5 in 1000 children born in developed countries, that is about 250 children every year in Switzerland. The primary cause of cerebral palsy is a brain lesion occurring shortly before or after birth. The brain lesion is static and does not progress with time but secondary consequences, such as joint contractures and bony deformities develop during childhood and adolescence. A variety of surgical interventions and orthotics prescriptions may be performed to improve the biomechanical capacity of the musculoskeletal system once the deformities have developed.

However, ethical and practical difficulties to organise randomised controlled trials within the field of surgery have led to low or moderate level of evidence to support the interventions. In addition, different patients may respond markedly differently to the same treatment. In this context, the principles of evidence-based medicine are difficult to apply by clinicians when choosing the most appropriate treatment for a given child, or when discussing their rationale with the families.

Since the 90s, instrumented gait analysis has been utilised to inform the clinical decision-making process, plan the details of surgical interventions when these are deemed necessary, and evaluate the outcome of these interventions. Instrumented gait analysis provides quantitative and objective measures of the walking function. It generates a rich dataset composed of more than 50 scalar values describing the lower limb anatomy and functioning as well as more than 80 waveforms describing the walking pattern of the patients.

In this project, routine clinical data collected in two leading gait analysis centres at the UKBB (Basel) and at the HUG (Geneva) will be connected to the SPHN infrastructure. The objectives of the project are to ensure the SPHN | Swiss Personalized Health Network 2 | 4 interoperability of gait analysis data collected in different clinical centres in Switzerland and internationally, to determine the causal treatment effect of some of the most common orthopaedic treatments to improve walking in children with cerebral palsy, and to quantify the added value of multicentric observational datasets.

This project aims to lay the foundation for national, and international, gait analysis data interoperability as well as support evidence-based clinical decision-making in the field of neuro-orthopaedics for children with cerebral palsy. 

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.

Toe walking after the age of three years is considered abnormal. It is termed idiopathic toe walking (ITW) in the absence of a neurological or orthopedic condition. Children with ITW present with reduced ankle mobility, impaired balance, sensory issues, difficulties in motor control, and increased fall risk. There is a need to diagnose ITW in a holistic manner and improve the monitoring of interventions. The aim of our project is to get a better understanding on how ITW may affect dynamic stability to tackle these issues.

We explore if dynamic stability is altered during walking in children with ITW compared to typically developing (TD) peers and if there exists the possibility to identify dynamic biomarkers based to support diagnostics and therapeutic management

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