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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.

BASEC-ID: 2024-00652

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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.