Quick, Tom JH; (2018) The clinical assessment of re-innervated motor function. Masters thesis (M.D(Res)), UCL (University College London).

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Abstract

Background: Muscle paralysis occurring due to nerve injury is a common clinical presentation. Reinnervation of skeletal muscle can occur spontaneously, or require surgical treatment. The return of movement after re-innervation occurs slowly, and never attains normal function (Birch & Quick 2016). Methods commonly used to assess this recovery of function have not changed significantly for over 7 decades. This study addresses the way re-innervated muscle function is assessed and how this might be improved. Muscle re-innervation is in itself an important clinical aim; but, as muscle re-innervation occurs through a process of nerve regeneration, its assessment could also potentially present a method for study of this biologic process: That is to say that the clinical assessment of muscle function can be viewed as a surrogate for the success of nerve regeneration. This thesis builds from a review of the historic approach to muscle assessment towards more modern methods for establishing validated outcomes for skeletal muscle motor re-innervation in humans. For use both as a research tool and as a nuanced clinical assessment for patients with nerve injury. The traditional method used to assess muscle function has been to focus only on one aspect of force: the assessment of peak force, and to use a discrete ordinal assessment for this (the MRC, Medical Research Council grading of force). This approach is discussed in chapter three. A review of the historic literature (chapter two) demonstrates that motor recovery is a complex phenomenon, and even in the area of peak force assessment; there is much to be improved upon. The benefits of utilising a continuous measurement of force rather than the discrete MRC scale are described, and then, in Chapter six, deployed in the clinical environment to examine outcome. The characterisation of the severity of human nerve injury, in its vast variation, presents an unmet clinical challenge. There is no method available which characterises the injury in any way other than in a piecemeal way, and no method which standardises clinical outcome across the many modalities of nerve injury. To address this the operation of ‘nerve transfer’ is presented (in chapter 4) as an ideal ‘standard model’ for the study of human nerve regeneration. The history and development of nerve transfer are described and the utility of viewing this operation as a controlled experiment set out: Nerve transfer is a complete, intentional, iatropathic, injury to a pure motor nerve with a single motor outcome. In this operation a nerve injury is created by disconnecting an expendable function to improve a more desirable function through the re-growth of nerves into this muscle. It is a discrete intervention which is undertaken to lead to an isolated improvement of a single assessable motor function. The methods in current use to assess re-innervated muscle function are explored in chapter five where a cohort of international experts were invited to contribute. This study (n= 18) displays and describes the responses of national leaders in this speciality from 10 countries. The results show that MRC grade is the universal assessment standard, and yet this specialist group recognise the need for more in depth assessments of motor function. Only 17% (n=3) agreed that the MRC system was very useful for a thorough assessment of force, whereby 45% considered peak force to be the most useful assessment of muscle function. There was acceptance of the method of using continuous force to assess maximal volition force. Chapter six presents a study whereby the expert cohort agreement for the need for continuous assessment of peak force outcomes (from chapter five) are applied to a cohort of patients who have undergone nerve transfer to return elbow bending force. These data, have been published in the eminent peer reviewed Bone and Joint Journal (BJJ). This publication was recognised by peers as the first clinic based publication deploying a continuous measure of outcome for this procedure. The results demonstrate similar findings to the only other cohort study Carlsen 2011) (where patients were assessed in an engineering laboratory). This study demonstrated validity of the clinical use of Hand Held dynamometry for assessment. The data described a population of outcomes whereby the mean was 7.2 KgF ±3.3. If a continuous measure of force is to be the method used to (as presented in chapter six) to study the impact of any novel difference in care to improve outcome: It is important to determine the degree of improvement which would be characterised as clinically relevant. This concept is termed the Minimum Clinical Important Difference (MCID). There are many suggested methods within a wide literature on this subject and it is accepted that they return a widespread of responses. The calculations in this chapter have been based upon published methods and include recommendations from the IMMPACT (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials) consensus document, patient anchor data, expert Delphi and statistical distribution methods. The results of which have provide a wide range of MCID (from 793gF- 6.52KgF); such a spread of data is typical in research into this area. Having taken the expert objective view that peak force is still considered a key outcome parameter; a study was performed (described in chapter eight) to explore the subjective experience of motor outcome. It has been explored whether peak force is an outcome considered relevant by patients. A questionnaire of satisfaction with outcome is undertaken with a group of individuals who have undergone muscle re-innervation (having had a nerve transfer to restore elbow flexion). The results of this are that the single outcome of peak force is not seen (by patients) as directly related to outcome nor correlated with the patients’ satisfaction. The results of the quantitative study in chapter eight are explored in more depth in chapter nine through a qualitative methodology: To explore the subjective experience in more depth a review of a group discussion between patient-participants was assessed in chapter nine; using the widely used methodological approach of phenomenology. These data highlight the ‘lived experience’ of motor recovery: highlighting the issue of fatigue, and also the problem of co-contraction. (Fatigue being the symptom of a feeling of loss of sustainability of force over time and co-contraction is a symptom of other muscles acting against the indented action to weaken the effect for a given force of another muscle.) In view of the contribution from the subjective qualitative and quantitative studies (chapters eight and nine) the original study (chapter six) is revisited in chapter ten with a novel cohort and re-designed to include assessments of fatigue and co-contraction. Novel data regarding the function of re-innervated muscles was produced using the hand-held dynamometer assessment (as described in chapter six) in conjunction with surface EMG measurements. It was shown in this study that re-inner-vated muscle has a lesser median EMG biceps frequency (-22.35Hz t=0.005) suggesting a change in the muscle type from the normal controls. There was no difference in rates of co-contraction (-2.3% t=0.698) in an unfatigued single maximal volitional contraction. There was no sign of fatigue seen in the biceps under repetitive contraction (an accepted model of 3 sequential maximal attempts). Under sustained contraction (>80% maximal force sustained for 60seconds) the force was maintained in both re-innervated biceps and the controls. The degree of co-contraction in reinnervated arms under sustained force was greater than that of the controls (at 25.6% vs 15.6%) but this decreased to a normal level (14.5%) with fatigue (this change did not reach significance however t=0.101). The re-innervated biceps were seen to fatigue however via a drop in the median frequency (-12.343Hz t=0.001) prior to any such change in the control population of non nerve-injured muscles (3.15Hz t=0.343). Thus demonstrating an earlier fatigue and pointing towards potential mechanisms for this via a change in the muscle fibre type (more fatigable) and a trend suggesting a contribution from afferent control and co-contraction. // Methods: A mixed methodological approach; of qualitative and quantitative methods, have been undertaken in this study. Chapters six and ten are quantitative assessments of outcomes in a cohort of patients who have undergone a nerve transfer to elbow flexion. Peak power is assessed in chapter six using a hand held dynamometer in chapter ten this is used in conjunction with surface EMG assessments. A Delphi method is used in chapter five to poll experts in the field on their practice and opinions of assessing motor recovery. The MCID calculations in chapter seven are undertaken by an assessment of Qualitative data in a number of ways to quantify and estimate based on a number of approaches, this varied method widely used in the literature produces a spread of results. // Summary: This thesis is a structured investigation of the key issues in motor recovery following nerve injury. The thesis is cyclical; and returns (in chapter ten) to, improve upon, the original study (chapter six) design to hone the question and produce a more informative, valid set of results; relevant to the patient cohort. Re-innervated muscle function is a subjectively complex experience however there are themes of fatigue, co-contraction and pain which are not commonly assessed. Experts and patients agree we should move on from purely relying on the MRC 5 point scale to describe the complex phenomenon of re-innervation muscle function. It has been demonstrated that hand held dynamometry and sEMG provide a method to assess peak force, fatigability and co-contraction. This provides an assessment that correlates with the issues deemed most pertinent by an expert group and most relevant by a patient cohort.

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