Upper Limb Movement After Hemispherectomy

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Upper Limb Movement After Hemispherectomy Upper Limb Movement After Hemispherectomy David Robert Henry Nobbs UCL Thesis submitted for the degree of DOCTOR OF PHILOSOPHY 1 I, David Robert Henry Nobbs, confirm the work presented in this thesis is my own. Where information has been derived from other sources, I confirm this has been indicated in the thesis. 1st March 2018 Signed: ................................. Date: ........................................ 2 Abstract Hemispherectomy is a surgical procedure for treating intractable epilepsy, involving the removal or disconnection of a cerebral hemisphere. Prior to surgery, patients have weakness along one side of their body and disruptions to their motor control. These impairments can be further exacerbated by the operation. This thesis provides an investigation into upper limb movement after surgery in terms of gross motor control and ipsilateral descending motor pathways for distal function. A neurophysiological assessment was used to identify the pathway driving the distal muscles of the paretic upper limbs. The results support the findings of previous studies that suggest superior function is likely to be dependent on a common, branching corticospinal pathway to the left and right sides. In addition, one patient without evidence of a common pathway had some use of the paretic wrist suggesting the presence of a distinct ipsilesional – possibly corticoreticulospinal – pathway. Upper limb kinematics during functional unimanual and bimanual reaching was also assessed. Unimanual deficits were identified and abnormalities in inter-limb coordination were found. These include a tendency to perform bimanual reaches as sequential unimanual reaches and reduced spatial interference in the trajectories of the two limbs. Whilst there were significant differences between the comparison and patient groups for these measures, there was also significant variance between the patients, underlining the heterogeneity of this cohort. 3 Impact statement The results of the studies in this thesis are expected to impact academic research into ipsilateral motor control after hemispherectomy. Firstly, neurophysiological studies can be pursued to further understand the two potential patterns of motor reorganisation that may underlie distal upper limb function. Secondly, neuroimaging studies can be pursued to understand the neural structures and connectivity involved in bimanual coordination with a single hemisphere. The results of this thesis have already been communicated to academic audiences through poster presentations at academic conferences. The results are planned to be disseminated further through the submission of manuscripts to academic journals. Furthermore, the methods used in this thesis can impact the clinical motor assessment of patients who undergo hemispherectomy. The positive findings of the neurophysiological assessment can impact the pre-operative assessment of hemispherectomised patients. The results of the kinematic assessment demonstrate its feasibility as a performance outcome measure of functional reaching in hemispherectomised patients that can be used in clinical practice. The results have already been communicated beyond academia through talks at epilepsy workshops involving clinicians from many different areas. In the future the validity and reliability of the methodologies can be established through collaborations with healthcare professionals working in the pre- and post- operative assessment of hemispherectomy candidates. 4 Acknowledgments I would like to thank my supervisors, Professor Faraneh Vargha-Khadem, Dr Luc Berthouze and Professor Helen Cross for sharing their knowledge, giving me their time and guiding me throughout this project. I also greatly appreciate the assistance of all those on the Epilepsy Surgery Programme at Great Ormond Street Hospital. They not only provide an excellent clinical service, but are also passionate about research. I am grateful to those colleagues that assisted in data collection and provided feedback on the results, including Linda Hammett, Simon Farmer, Margaret Mayston, Alki Liasis, Sian Handley, Tina Banks, Jessica Cooper and Sebastian Guderian. I have received help and advice from many in the Cognitive Neuroscience and Neuropsychiatry Department at the Institute of Child Health, UCL. In particular, I would like to thank Torsten Baldeweg, Frederique Liegeois, Serife Dervish, Ania Dzieciol, Joe Bathelt, Sharon Geva, Georgia Pitts and Zita Patai. I would like to thank my family for their patience and encouragement. Finally, I wish to express my gratitude to all those who took part in this study, especially the patient participants. It was a great pleasure to meet them. By giving their time to research, they make possible the advances that are made in the field. This thesis was funded by a Child Health Research Appeal Trust studentship. 5 Table of Contents Abstract ..................................................................................................................... 3 Impact statement ...................................................................................................... 4 Acknowledgments .................................................................................................... 5 1. General introduction ...................................................................................... 12 1.1 Hemispherectomy as treatment for intractable epilepsy ........................... 12 1.2 Existing measures of upper limb function ................................................. 16 1.3 Optical motion capture .............................................................................. 18 1.4 Ipsilateral motor control ............................................................................ 21 1.4.1 Corticospinal projections ................................................................... 21 1.4.2 Pathways from the brainstem ........................................................... 24 1.4.3 Brainstem projections and hand function .......................................... 26 1.4.4 Pre-surgical assessment ................................................................... 28 1.5 Remainder of the thesis ............................................................................ 29 2. Clinical assessments ..................................................................................... 33 2.1 Introduction ............................................................................................... 34 2.2 Participants ............................................................................................... 35 2.3 Methodology ............................................................................................. 36 2.3.1 Clinical histories ................................................................................ 36 2.3.2 Motor tests ........................................................................................ 36 2.3.3 Visual tests ........................................................................................ 37 2.4 Results ...................................................................................................... 40 2.4.1 Clinical history: C.B. .......................................................................... 40 2.4.2 Clinical history: D.N. .......................................................................... 42 2.4.3 Clinical history: E.B. .......................................................................... 44 2.4.4 Clinical history: H.W. ......................................................................... 47 2.4.5 Clinical history: J.S. ........................................................................... 49 2.4.6 Clinical history: P.O. .......................................................................... 51 2.4.7 Motor tests ........................................................................................ 54 2.4.8 Visual tests ........................................................................................ 55 2.5 Discussion ................................................................................................ 61 2.5.1 Clinical histories ................................................................................ 61 2.5.2 MRI scans ......................................................................................... 61 2.5.3 Motor performance ............................................................................ 62 6 2.5.4 Visual performance ........................................................................... 63 2.5.5 Conclusions ...................................................................................... 64 3. Neurophysiological assessment of motor pathways .................................. 65 3.1 Introduction ............................................................................................... 66 3.1.1 Motor pathways after early brain damage ......................................... 67 3.1.2 Branching pathways .......................................................................... 68 3.1.3 Neurophysiological evidence for branching pathways ...................... 69 3.1.4 Correlations in the frequency domain ............................................... 73 3.1.5 Mirror movements and hemispherectomy ......................................... 74 3.2 Methodology ............................................................................................. 76 3.2.1 Participants ....................................................................................... 76 3.2.2
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