Freezing of Gait in Parkinson's Disease
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PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/93606 Please be advised that this information was generated on 2021-10-05 and may be subject to change. Tackling freezing of gait in Parkinson’s disease freezing of gait in Parkinson’s Tackling Tackling freezing of gait in Parkinson’s disease Anke H. Snijders ANKE H. SNIJDERS ISBN 978-94-91027-33-8 90 Tackling freezing of gait in Parkinson’s disease Anke H. Snijders ‘like the wheels of a locomotive failing to bite the rails when they are slippery with frost and making, in consequence, ineffective revolutions’ William W describing his gait disorder, according to Thomas Buzzard, neurologist National Hospital Queen Square, London, 1882 The studies presented in this thesis were carried out at the Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience and Centre for Cognitive Neuroimaging, Radboud University Medical Centre, Nijmegen, the Netherlands, with financial support of the Prinses Beatrix Fonds, the Radboud University Medical Centre and the Netherlands Organization for Scientific Research (NWO), grant numbers 92003490 (A.H.Snijders) and 016076352 (B.R.Bloem). Cover design and layout by: In Zicht Grafisch Ontwerp, Arnhem Printed by: Ipskamp Drukkers, Enschede DVD layout and production by: Mimumedia, Nijmegen ISBN: 978-94-91027-33-8 ©2012 A.H. Snijders Tackling freezing of gait in Parkinson’s disease Proefschrift ter verkrijging van de graad van doctor aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. mr. S.C.J.J.Kortmann, volgens besluit van het college van decanen in het openbaar te verdedigen op maandag 4 juni 2012 om 13.30 uur precies door Anke Helene Snijders geboren op 9 juni 1979 te Groningen Promotor: Prof. dr B.R. Bloem Copromotor: Dr I. Toni Manuscriptcommissie: Prof. dr G. Fernandez Prof. dr A.C.H. Geurts Prof. dr A. Nieuwboer (KU Leuven) Tackling freezing of gait in Parkinson’s disease Doctoral thesis To obtain the degree of doctor from Radboud Universiteit Nijmegen on the authority of the Rector Magnificus, prof. dr. S.C.J.J.Kortmann, according to the decision of the Council of Deans to be defended in public on Monday, June 4, 2012 at 13.30 hours by Anke Helene Snijders Born on June 9, 1979 Groningen, Netherlands Supervisor: Prof.dr B.R. Bloem Co-supervisor: Dr I. Toni Doctoral Thesis Committee: Prof. dr G. Fernandez Prof. dr A.C.H. Geurts Prof. dr A. Nieuwboer (KU Leuven) Contents 1 | Outline of the thesis 9 2 | General introduction to gait disorders and freezing of gait 19 2.1 Neurological gait disorders in the elderly 21 2.2 Freezing of gait: general overview 45 3 | Provoking freezing of gait 59 3.1 Clinimetrics of freezing of gait 61 3.2 To freeze or not to freeze: clinical provocation of freezing of gait 75 3.3 Obstacle avoidance to provoke freezing of gait on a treadmilll 89 3.4 Objective detection of subtle freezing of gait in Parkinson’s disease 103 4 | Understanding freezing of gait 119 4.1 Gait-related cerebral changes in freezing of gait 121 5 | Cycling and freezing of gait 155 5.1 Cycling breaks the ice for freezing of gait 157 5.2 Cycling is less affected then walking in freezers of gait 167 6 | Treating freezing of gait 173 6.1 Cueing for freezing of gait: a need for 3D cues? 175 6.2 ‘ON-state’ freezing of gait in Parkinson’s disease: 181 A paradoxical levodopa-induced complication 7 | Summary & discussion 193 8 | Nederlands 209 8.1 Loopstoornissen 211 8.2 Wankel op de benen en vallen 225 8.3 Nederlandse samenvatting 235 8.4 Overzicht van de behandeling van bevriezen van lopen 243 A | 251 Appendix 1: Freezing of gait Scoring Form 253 Appendix 2: Abbreviations 256 Appendix 3: Reference list 257 Appendix 4: Video contents 273 Appendix 5: Video legends 274 Dankwoord 279 CV 283 List of publications 285 Donders Graduate School for Cognitive Neuroscience Series 287 Dissertations of the Parkinson Centre Nijmegen (ParC) 291 1| Outline of the thesis OUTLINE OF THE THESIS 1 Outline of the thesis Gait disorders and freezing of gait Gait disorders are common and often devastating companions of ageing, leading to reductions in quality of life and increased mortality.328;375;387 A curious feature of some gait disturbances is their fluctuating or frank episodic nature. An example of an incapacitating episodic gait disorder is freezing of gait (FOG), where patients feel like their feet are ‘glued to the floor’. FOG is frequently seen in patients with Parkinson’s disease (PD: Box 1), with unexpected episodes during which patients experience an inability to start walking or to continue moving forward.150 Because of this sudden and unpredictable nature, FOG is an important cause of falls and injuries.201;219 Vignettes A remarkable observation in a single patient can sometimes help to advance the field, by generating new ideas for further research. Therefore, each chapter of this thesis starts with a short vignette presenting an intriguing video, as a source of inspiration and contemplation. This thesis will start with a general introduction of gait disorders in Chapter 2.1, discussing its pathophysiology, core clinical features and assessment. We propose a Box 1 Parkinson’s disease Parkinson’s disease (PD) is a degenerative disorder with abnormalities of movement, behaviour, learning and emotions, mainly due to dopaminergic deficiency of the striatum (caudate nucleus and putamen in the basal ganglia). The pathognomonic pathological feature of PD is the presence of intraneuronal inclusions (pale bodies and Lewy bodies), mainly containing α-synuclein. This pathology affects not only the dopaminergic neurons, but also noradrenergic, cholinergic, serotonergic and other central neurotransmitter systems. The main motor features of PD result from dopaminergic deficiency in the striatum (caudate nucleus and putamen): tremor, rigidity, bradykinesia (slowing down of movements) and hypokinesia/akinesia (scarcity/absence of movements). However, non-motor signs and symptoms are increasingly recognized in PD, including fatigue, hyposmia, pain, autonomic dysfunctions, mood disorders, sleep disorders and cognitive deficits. Mainstay of treatment are levodopa, dopamine agonists and deep brain stimulation. All these therapies are symptomatic treatments: they do not stop the neurodegeneration itself. To date, there is no treatment that cures the disease. Also, there is no evidence for neuroprotective medications to slow down the disease.1;53;322 13 CHAPTER 1 Box 1 Continued ( From: Bear, M. F., Connors, B.W. & Paradiso M. A., Neuroscience: Exploring the Brain, Second Edition, Lippincott Williams & Wilkins, 2001, pp 473-482.) practical three-step approach to categorise gait disorders and we present a simplified classification system based on clinical signs and symptoms. Then, I will give a general overview of freezing of gait in Chapter 2.2. Provoking freezing of gait FOG is an unusual gait disorder because of its “episodic” character: the gait problem is sometimes there, but often it is not. This makes FOG a challenge for clinicians. Many patients inadvertently deny having FOG gait because they do not properly know what actual freezing looks like. Even when patients report having FOG at home, the phenomenon is notoriously difficult to elicit in the clinical setting.288 Apparently, excitement associated with the doctor’s visit or the patient’s extra attention to gait during physical examination can temporarily suppress FOG (a form of “kinesia paradoxa”). Another explanation is that FOG, which is typically provoked while walking in tight quarters,329 is less likely to occur in a widely spaced hospital corridor than at home in a crammed living room. This failure to demonstrate the problem that hinders 14 OUTLINE OF THE THESIS 1 them so much at home is very frustrating for patients and carers. It is also inconvenient for doctors who need to base their clinical management decisions based on observations in the examination room. Besides, it hinders patient inclusion in research studies. Hence, we have tried to find ways to provoke FOG. In the section “Provoking freezing of gait” we start with Chapter 3.1, a review on the clinimetry of FOG. Then Chapter 3.2 deals with the best way to clinically provoke FOG, followed by Chapter 3.3 and 3.4 on the provocation and detection of FOG on a treadmill. Understanding freezing of gait The mechanisms leading to FOG remain poorly understood, and this hampers development of improved treatment strategies. In Chapter 4, we used motor imagery of gait in combination with fMRI (Box 2) to study the cerebral correlates of gait planning in patients with and without FOG. Box 2 fMRI and motor imagery fMRI: functional Magnetic Resonance Imaging is a type of specialized MRI scan. It measures the hemodynamic response (change in blood flow) related to neural activity in the brain. To do so, it measures the blood-oxygen-level dependence (BOLD), the MRI contrast of blood deoxyhemoglobin. Advantages are its relatively low invasiveness, absence of radiation exposure, wide availability and high spatial resolution. Still, images must be interpreted carefully, as correlation does not imply causality. Rigorous statistical analyses are needed to avoid false positives. In addition, temporal resolution in poor. Motor imagery: During motor imagery a particular movement is imagined but not executed.193 There is a large functional and neural overlap between motor planning and motor imagery.77;193;251 Several issues are important when using motor imagery to study real movement in PD: - Motor imagery relies on the current physical configuration of a subject. For example, motor imagery in patients with amputated limb is delayed,282 and hand position influences the ability to mentally rotate hands.89 - Motor imagery is sensitive to motor control variables.