Axial!postural! deformities!in! Parkinson’s!disease! Thesis submitted in fulfilment of the degree of Doctor of Medicine (Research) Reta Lila Weston Institute of Neurological Studies UCL Institute of Neurology University College London 2013 Karen M. Doherty ! 1 ! I, Karen M. Doherty confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Signed: Date: ! 2 ! Abstract Studies have been performed to detail the phenomenology, investigate the skeletal changes and explore the spinal biomechanics underlying the main axial deformities – Pisa syndrome and camptocormia in Parkinson’s disease. Results demonstrate that the clinical picture of these deformities varies greatly but that certain particular features allow distinction from other neurological, muscular and bony aetiologies. The tone of the axial muscles, the level at which spinal flexion occurs, the patient’s ability and method to try to overcome the chronically abnormal posture, and the flexibility or fixity of the trunk provide clinical pointers to the likely underlying cause. The scoliotic curve in a patient with Pisa syndrome was C-shaped, involved a large element of collapse and occurred without evidence of a secondary upper compensatory curvature (S-shaped curve). On supine imaging patients with camptocormia were severely mechanically disadvantaged as a result of their alordotic lumbar spines in relation to pelvic angulation. This lumbar alordosis may reflect the effects of Parkinson’s disease on the axial musculature, particularly in those with axial akinetic rigid predominant PD. Radiological examination also demonstrated that Pisa syndrome was different from de novo degenerative scoliosis and camptocormia not typical of adult onset degenerative kyphosis. Fixed bony changes were rare but the severity of these postural deformities and their consequent effects (e.g. knee flexion contractures, gluteal muscle atrophy) are likely to render conservative interventions unsuccessful unless instigated very early in the evolution of the abnormal posture. ! 3 ! Papers associated with thesis Doherty KM, van de Warrenburg BP, Peralta MC, Silveira-Moriyama L, Azulay JP, Gershanik OS, Bloem BR. 2011. Postural deformities in Parkinson’s disease. Lancet Neurol, 10(6):538-49. Doherty KM, Noyce AJ, Silveira-Moriyama L, Nisbet A, Quinn N, Lees AJ. 2012. Familial camptocormia: from dystonia to myopathy. J Neurol Neurosurg Psychiatry, 83(3):350-1. Doherty KM, Silveira-Moriyama L, Giladi N, Bhatia KP, Parton M, Lees AJ. 2012. Camptocormia: don’t forget muscle disease in the movement disorder clinic. J Neurol, 259(8):1752-4. Doherty KM, Davagnanam I, Molloy S, Silveira-Moriyama L, Lees AJ. 2013. Pisa syndrome in Parkinson’s disease: a mobile or fixed deformity? J Neurol Neurosurg Psychiatry, Published Online First: 26 March doi:10.1136/jnnp-2012-304700. ! 4 ! Other papers published during research period Ling H, Braschinsky M, Taba P, Luus SM, Doherty K, Hotter A, Poewe W, Lees AJ. 2011. Decades of delayed diagnosis in 4 levodopa-responsive young-onset monogenetic parkinsonism patients. Mov Disord, 26 (7): 1337-1340. Djamshidian A, O’Sullivan SS, Doherty K, Lees AJ, Averbeck BB. 2011. Altruistic punishment in patients with Parkinson’s disease with and without impulsive behaviour. Neuropsychologia, 49(1):103-7. *Ahmed Z, *Doherty KM, Silveira-Moriyama L, Bandopadhyay R, Lashley T, Mamais A, Hondhamuni G, Wray S, Newcombe J, O'Sullivan SS, Wroe S, de Silva R, Holton JL, Lees AJ, Revesz T. 2011. Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: An emerging group of 4-repeat tauopathies. Acta Neuropathol, 122(4):415-28. (*joint first author) Djamshidian A, O'Sullivan SS, Sanotsky Y, Sharman S, Matviyenko Y, Foltynie T, Michalczuk R, Aviles-Olmos I, Fedoryshyn L, Doherty KM, Filts Y, Selikhova M, Bowden-Jones H, Joyce E, Lees AJ, Averbeck BB. 2012. Decision making, impulsivity, and addictions: do Parkinson's disease patients jump to conclusions? Mov Disord, 27(9):1137-45. Doherty KM, Rohrer JD, Lees AJ, Holton JL, Warren J. 2013. Primary progressive aphasia with parkinsonism: Clinicopathological case. Mov Disord, 28(6):741-6. Doherty KM, Silveira-Moriyama L, Parkkinen L, Healy DG, Farrell M, Mencacci NE, Ahmed Z, Brett FM, Hardy J, Quinn N, Counihan TJ, Lynch T, Fox ZV, Revesz T, Lees AJ, Holton JL. 2013. Parkin Disease – A clinicopathological entity? JAMA Neurol, 70(5):571-9. Doherty KM, Hardy J. Parkin disease and the Lewy body conundrum. 2013, Mov Disord, 28(6):702-4. ! 5 ! List of abbreviations 6-OHDA 6-Hydroxydopamine ANOVA Analysis of Variance AP Anterior-posterior CI Confidence interval COX cyclo-oxygenase CK creatine kinase COMTi Catechol-O-methyl transferase inhibitor CT Computerised tomography DA Dopamine agonist DaTSCAN Dopamine transporter scan DBS Deep brain stimulation DLB Dementia with Lewy bodies DNA Deoxyribonucleic acid EMG Electromyography FAB Frontal assessment battery FES Functional electrical stimulation FSHD Facioscapulohumeral muscular dystrophy H&Y Hoehn and Yahr ! 6 ! IoN Institute of Neurology L-dopa L-3,4-dihydroxyphenylalanine LEDD L-dopa equivalent daily dose LED L-dopa equivalent dose LSVT Lee Silverman voice treatment MAO-Bi Monoamine oxidase B inhibitor MDS Movement Disorder Society MoCA Montreal cognitive assessment MPTP 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MRI Magnetic resonance imaging MSA Multiple system atrophy MUPs Motor unit (action) potentials MWU Mann-Whitney U test NHNN National Hospital for Neurology and Neurosurgery PD Parkinson’s disease PIGD Postural instability/gait difficulty PSP Progressive supranuclear palsy QSBB Queen Square Brain Bank RA rectus abdominis RF Royal Free ! 7 ! SD Standard deviation SDH Succinate Dehydrogenase TPAD thoraco-pelvic anterior distraction UCL University College London UCLH University College London Hospitals UK United Kingdom UPDRS Unified Parkinson’s Disease Rating Scale VAS Visual analogue scale ! 8 ! Table of Contents ABSTRACT!...................................................................................................................................................!3! PAPERS!ASSOCIATED!WITH!THESIS!....................................................................................................................!4! OTHER!PAPERS!PUBLISHED!DURING!RESEARCH!PERIOD!.........................................................................................!5! LIST!OF!ABBREVIATIONS!.................................................................................................................................!6! TABLE!OF!CONTENTS!.....................................................................................................................................!9! LIST!OF!TABLES!..........................................................................................................................................!12! LIST!OF!FIGURES!.........................................................................................................................................!13! Chapter 1: Postural deformities in Parkinson’s disease – a review of the literature ......................... 14! INTRODUCTION!..........................................................................................................................................!14! Overview'of'thesis'............................................................................................................................'14! Parkinson’s'disease'...........................................................................................................................'14! Postural'deformities'in'Parkinson’s'disease'.....................................................................................'16! Methodology,'search'strategy'and'selection'criteria'.......................................................................'17! SAGITTAL!PLANE!DEFORMITIES!......................................................................................................................!18! Camptocormia'..................................................................................................................................'18! Antecollis'..........................................................................................................................................'27! Retrocollis'.........................................................................................................................................'30! CORONAL!PLANE!DEFORMITIES!......................................................................................................................!31! Pisa'syndrome'&'scoliosis'.................................................................................................................'31! PATHOPHYSIOLOGY!OF!PARKINSONIAN!POSTURAL!DEFORMITY!.............................................................................!35! Central'mechanisms'.........................................................................................................................'35! Peripheral'mechanisms'....................................................................................................................'41! CONCLUSION!.............................................................................................................................................!43! Chapter 2: Clinical spectrum of axial deformities of the trunk in Parkinson’s disease ..................... 45! INTRODUCTION!..........................................................................................................................................!45!