Published Ahead of Print on September 27, 2017 as 10.1212/WNL.0000000000004581
EDITORIAL
Virtually reducing fall risk in Parkinson disease
Caroline Moreau, MD, PhD Brandon R. Barton, MD, MS David Devos, MD, PhD
Correspondence to Dr. Devos: [email protected] Neurology® 2017;89:1–2
Falls are common and often represent devastating events for patients with advanced Parkinson disease (PD). Prospective studies report that 70% of people with PD have at least one fall in a year, and that 39% fall recurrently. Falls have serious consequences (fractures and other injury, hospital admission, fear of falls, and an increase in caregiver burden).1,2 The few available treatment options are not highly effective. Falls in PD have 3 main causes: freezing of gait (for forward falls), postural instability (for backward falls), and obstacle negotiation (poor foot clearance or a lack of attention, mostly for forward falls). The latter category may involve motor impairments (i.e., akinesia caused by a lack of dopamine and thus fault in the basal ganglia circuitry) or cognitive impairments (involving the cortico-striato-prefrontal circuitry). In routine clinical practice, physiotherapy constitutes the main management strategy for falls prevention. However, data on the efficacy of intensive physiotherapy for treating the causes of falls and preventing further falls in PD remain conflicting and inconclusive. For example, a study of a small group of patients by Sparrow et al.3 demonstrated that a 3-month period of active balance exercises reduced the risk of falls by 37%. Conversely, a recent Class III randomized study of 231 patients with PD failed to demonstrate a reduction in the fall rate or the proportion of fallers after 6 months of intensive exercise (40–60 minutes, 3 times a week), relative to standard care.4 Although behavioral studies have suggested that the cognitive and sensorimotor impairments associated with PD impair the ability to walk in complex environments, few have studied or applied cognitive rehabilitation or the combination of cognitive rehabilitation and physiotherapy to address fall risk in PD.5 Mirelman et al.6 first investigated the benefit of motor-cognitive training on falls during obstacle negotiation in patients with PD. In the current issue of Neurology®, this group extends that work by analyzing the associated brain activation pattern.7 These investigators identified neural correlates of plasticity using functional MRI imagery of locomotion in
a complex environment based on a multimodal treadmill training (TT) program augmented by virtual reality (VR).7 The study’s results suggest that the TT 1 VR combination has advantages over TT alone.6 From a pathophysiologic point of view, this highly relevant study specified the brain network involved in gait in a complex environment. Prior data indicate that (1) the cerebellum participates in movement coordination, (2) the middle temporal gyrus participates in sensory integration, and (3) the frontal network (including Brodmann area 10 and the inferior frontal gyrus) participates in the executive function and obstacle negotiation associated with multitasking, planning, attention, and inhibition. The participants in the TT 1 VR arm showed a greater improvement (relative to the TT group) in the attention score and in gait speed during obstacle negotiation, in parallel with changes in brain network activation. After training, participants in the TT 1 VR arm showed less activation in the frontal areas than participants in the TT arm, whereas the participants in the TT arm showed less activation in the cerebellum and middle temporal gyrus.7 Mirelman et al. concluded that exercise seems to modify brain activation patterns in patients with PD in a specific manner: the motor and cognitive training decreased the reliance on frontal regions, which resulted in improved function and might reflect an increase in brain efficiency. From a scientific point of view, this study provides several key messages. Cognition plays a pivotal role in falls, supported by the concomitant occurrence of falls and cognitive disorders in advanced PD. Cognitive rehabilitation improves the effect of motor rehabilitation on falls. The study’s findings reinforce the hypothesis that training improves motor and cognitive automaticity through neuroplasticity and enhanced activity in the striatal thalamic cortical loops, and thus reduces the need for cortical activation as a compensatory mechanism. A VR gait program with obstacles enhances cognitive performance and thus reduces the requirement for prefrontal activity, whereas TT improves sensorimotor feedback.
See page 1804 From the Service de Neurologie (C.M., D.D.) and Services de Pharmacologie and Médicale (D.D.), LICEND COEN Center, Université de Lille, CHU de Lille, INSERM UMRS_1171, France; Department of Neurological Sciences (B.R.B.), Rush University Medical Center; and Neurology Service (B.R.B.), Jesse Brown VA Medical Center, Chicago, IL. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the editorial. © 2017 American Academy of Neurology
ª 2017 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
1
Of course, this pivotal study also raises several issues and highlights needs for further investigation. Future studies need to characterize the cognitive profile of patients with PD better in order to determine predictors of a better response. A comprehensive neuropsychological assessment might show evidence of cognitive benefits of a TT 1 VR program. Longitudinal studies will need to establish the long-term effectiveness of a TT 1 VR program in order to provide recommendations for patient management. Testing if the areas activated during an imagined obstacle negotiation in a virtual world correspond to those during actual physical activity is needed. Finally, future studies need to test if early intervention of this type could yield greater benefit (e.g., by assessing early markers of the risk of falls).8 The results of Mirelman et al. suggest that cognitive-motor training may reduce impairments (and particularly falls) in patients with advanced PD, with potential implications for routine clinical practice. However, most patients will not have access to VR equipment for rehabilitation. For a larger proportion of patients with PD, training in real, everyday, complex situations (e.g., the patient goes shopping in town) may prove easier to implement, albeit with a need to ensure safety and likely require an accompanying caregiver or physiotherapist. Finally, the Rivastigmine for gait stability in patients with Parkinson’s disease (ReSPonD) trial showed a reduction of falls in those treated with rivastigmine (12 mg/d),9 and the Study of Methylphenidate to Treat Gait Disorders And Attention Deficit In Parkinson’s Disease (PARKGAIT-II) trial showed a reduction in freezing gait (and probably falls related to freezing) in those treated with methylphenidate (1 mg/kg/d).10 It remains to be seen whether cognitive therapy, motor training, and pharmacologic treatment have synergistic effects on reducing the risk of falls. STUDY FUNDING No targeted funding reported.
DISCLOSURE Caroline Moreau served on the scientific advisory board for Aguettant, Orkyn, AbbVie, and ApoPharma, and has received research funding from
2
Neurology 89
the France Parkinson charity and honoraria from pharmaceutical companies for consultancy and lectures. Brandon R. Barton has received honoraria from pharmaceutical companies for consultancy. David Devos served on the scientific advisory board for Novartis, Aguettant, Orkyn, AbbVie, and ApoPharma, and has received PHRC grants from the French Ministry of Health, research funding from the France Parkinson charity, and honoraria from pharmaceutical companies for consultancy and lectures. Go to Neurology.org for full disclosures.
REFERENCES 1. Allen NE, Schwarzel AK, Canning CG. Recurrent falls in Parkinson’s disease: a systematic review. Parkinsons Dis 2013;2013:906274. 2.
Low V, Ben-Shlomo Y, Coward E, Fletcher S, Walker R, Clarke CE. Measuring the burden and mortality of hospitalisation in Parkinson’s disease: a cross-sectional analysis of the English Hospital Episodes Statistics database 2009–2013. Parkinsonism Relat Disord 2015;21:449–454.
3.
Sparrow D, DeAngelis TR, Hendron K, Thomas CA, Saint-Hilaire M, Ellis T. Highly challenging balance program reduces fall rate in Parkinson disease. J Neurol Phys Ther 2016;40:24–30.
4.
Canning CG, Sherrington C, Lord SR, et al. Exercise for falls prevention in Parkinson disease: a randomized controlled trial. Neurology 2015;84:304–312.
5.
Walton CC, Naismith SL, Lampit A, Mowszowski L, Lewis SJ. Cognitive training in Parkinson’s disease. Neurorehabil Neural Repair 2017;31:207–216.
6.
Mirelman A, Rochester L, Maidan I, et al. Addition of a non-immersive virtual reality component to treadmill training to reduce fall risk in older adults (V-TIME): a randomised controlled trial. Lancet 2016;388: 1170–1182.
7.
Maidan I, Rosenberg-Katz K, Jacob Y, Giladi N, Hausdorff JM, Mirelman A. Disparate effects of training on brain activation in Parkinson disease. Neurology 2017;89:1804–1810. Lord S, Galna B, Yarnall AJ, Coleman S, Burn D, Rochester L. Predicting first fall in newly diagnosed Parkinson’s disease: insights from a fall-naïve cohort. Mov Disord 2016;31:1829–1836. Henderson EJ, Lord SR, Brodie MA, et al. Rivastigmine for gait stability in patients with Parkinson’s disease (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 2016;15:249–258. Moreau C, Delval A, Defebvre L, et al; PARKGAIT-II study group. Methylphenidate for gait hypokinesia and freezing in patients with Parkinson’s disease undergoing subthalamic stimulation: a multicentre, parallel, randomised, placebo-controlled trial. Lancet Neurol 2012;11: 589–596.
8.
9.
10.
October 24, 2017
ª 2017 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
Virtually reducing fall risk in Parkinson disease Caroline Moreau, Brandon R. Barton and David Devos Neurology published online September 27, 2017 DOI 10.1212/WNL.0000000000004581 This information is current as of September 27, 2017 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/early/2017/09/27/WNL.0000000000 004581.full.html
Subspecialty Collections
This article, along with others on similar topics, appears in the following collection(s): All Rehabilitation http://www.neurology.org//cgi/collection/all_rehabilitation Assessment of cognitive disorders/dementia http://www.neurology.org//cgi/collection/assessment_of_cognitive_dis orders_dementia Parkinson's disease/Parkinsonism http://www.neurology.org//cgi/collection/parkinsons_disease_parkinso nism
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2017 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
EDITORIAL
Virtually reducing fall risk in Parkinson disease
Caroline Moreau, MD, PhD Brandon R. Barton, MD, MS David Devos, MD, PhD
Correspondence to Dr. Devos: [email protected] Neurology® 2017;89:1–2
Falls are common and often represent devastating events for patients with advanced Parkinson disease (PD). Prospective studies report that 70% of people with PD have at least one fall in a year, and that 39% fall recurrently. Falls have serious consequences (fractures and other injury, hospital admission, fear of falls, and an increase in caregiver burden).1,2 The few available treatment options are not highly effective. Falls in PD have 3 main causes: freezing of gait (for forward falls), postural instability (for backward falls), and obstacle negotiation (poor foot clearance or a lack of attention, mostly for forward falls). The latter category may involve motor impairments (i.e., akinesia caused by a lack of dopamine and thus fault in the basal ganglia circuitry) or cognitive impairments (involving the cortico-striato-prefrontal circuitry). In routine clinical practice, physiotherapy constitutes the main management strategy for falls prevention. However, data on the efficacy of intensive physiotherapy for treating the causes of falls and preventing further falls in PD remain conflicting and inconclusive. For example, a study of a small group of patients by Sparrow et al.3 demonstrated that a 3-month period of active balance exercises reduced the risk of falls by 37%. Conversely, a recent Class III randomized study of 231 patients with PD failed to demonstrate a reduction in the fall rate or the proportion of fallers after 6 months of intensive exercise (40–60 minutes, 3 times a week), relative to standard care.4 Although behavioral studies have suggested that the cognitive and sensorimotor impairments associated with PD impair the ability to walk in complex environments, few have studied or applied cognitive rehabilitation or the combination of cognitive rehabilitation and physiotherapy to address fall risk in PD.5 Mirelman et al.6 first investigated the benefit of motor-cognitive training on falls during obstacle negotiation in patients with PD. In the current issue of Neurology®, this group extends that work by analyzing the associated brain activation pattern.7 These investigators identified neural correlates of plasticity using functional MRI imagery of locomotion in
a complex environment based on a multimodal treadmill training (TT) program augmented by virtual reality (VR).7 The study’s results suggest that the TT 1 VR combination has advantages over TT alone.6 From a pathophysiologic point of view, this highly relevant study specified the brain network involved in gait in a complex environment. Prior data indicate that (1) the cerebellum participates in movement coordination, (2) the middle temporal gyrus participates in sensory integration, and (3) the frontal network (including Brodmann area 10 and the inferior frontal gyrus) participates in the executive function and obstacle negotiation associated with multitasking, planning, attention, and inhibition. The participants in the TT 1 VR arm showed a greater improvement (relative to the TT group) in the attention score and in gait speed during obstacle negotiation, in parallel with changes in brain network activation. After training, participants in the TT 1 VR arm showed less activation in the frontal areas than participants in the TT arm, whereas the participants in the TT arm showed less activation in the cerebellum and middle temporal gyrus.7 Mirelman et al. concluded that exercise seems to modify brain activation patterns in patients with PD in a specific manner: the motor and cognitive training decreased the reliance on frontal regions, which resulted in improved function and might reflect an increase in brain efficiency. From a scientific point of view, this study provides several key messages. Cognition plays a pivotal role in falls, supported by the concomitant occurrence of falls and cognitive disorders in advanced PD. Cognitive rehabilitation improves the effect of motor rehabilitation on falls. The study’s findings reinforce the hypothesis that training improves motor and cognitive automaticity through neuroplasticity and enhanced activity in the striatal thalamic cortical loops, and thus reduces the need for cortical activation as a compensatory mechanism. A VR gait program with obstacles enhances cognitive performance and thus reduces the requirement for prefrontal activity, whereas TT improves sensorimotor feedback.
See page 1804 From the Service de Neurologie (C.M., D.D.) and Services de Pharmacologie and Médicale (D.D.), LICEND COEN Center, Université de Lille, CHU de Lille, INSERM UMRS_1171, France; Department of Neurological Sciences (B.R.B.), Rush University Medical Center; and Neurology Service (B.R.B.), Jesse Brown VA Medical Center, Chicago, IL. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the editorial. © 2017 American Academy of Neurology
ª 2017 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
1
Of course, this pivotal study also raises several issues and highlights needs for further investigation. Future studies need to characterize the cognitive profile of patients with PD better in order to determine predictors of a better response. A comprehensive neuropsychological assessment might show evidence of cognitive benefits of a TT 1 VR program. Longitudinal studies will need to establish the long-term effectiveness of a TT 1 VR program in order to provide recommendations for patient management. Testing if the areas activated during an imagined obstacle negotiation in a virtual world correspond to those during actual physical activity is needed. Finally, future studies need to test if early intervention of this type could yield greater benefit (e.g., by assessing early markers of the risk of falls).8 The results of Mirelman et al. suggest that cognitive-motor training may reduce impairments (and particularly falls) in patients with advanced PD, with potential implications for routine clinical practice. However, most patients will not have access to VR equipment for rehabilitation. For a larger proportion of patients with PD, training in real, everyday, complex situations (e.g., the patient goes shopping in town) may prove easier to implement, albeit with a need to ensure safety and likely require an accompanying caregiver or physiotherapist. Finally, the Rivastigmine for gait stability in patients with Parkinson’s disease (ReSPonD) trial showed a reduction of falls in those treated with rivastigmine (12 mg/d),9 and the Study of Methylphenidate to Treat Gait Disorders And Attention Deficit In Parkinson’s Disease (PARKGAIT-II) trial showed a reduction in freezing gait (and probably falls related to freezing) in those treated with methylphenidate (1 mg/kg/d).10 It remains to be seen whether cognitive therapy, motor training, and pharmacologic treatment have synergistic effects on reducing the risk of falls. STUDY FUNDING No targeted funding reported.
DISCLOSURE Caroline Moreau served on the scientific advisory board for Aguettant, Orkyn, AbbVie, and ApoPharma, and has received research funding from
2
Neurology 89
the France Parkinson charity and honoraria from pharmaceutical companies for consultancy and lectures. Brandon R. Barton has received honoraria from pharmaceutical companies for consultancy. David Devos served on the scientific advisory board for Novartis, Aguettant, Orkyn, AbbVie, and ApoPharma, and has received PHRC grants from the French Ministry of Health, research funding from the France Parkinson charity, and honoraria from pharmaceutical companies for consultancy and lectures. Go to Neurology.org for full disclosures.
REFERENCES 1. Allen NE, Schwarzel AK, Canning CG. Recurrent falls in Parkinson’s disease: a systematic review. Parkinsons Dis 2013;2013:906274. 2.
Low V, Ben-Shlomo Y, Coward E, Fletcher S, Walker R, Clarke CE. Measuring the burden and mortality of hospitalisation in Parkinson’s disease: a cross-sectional analysis of the English Hospital Episodes Statistics database 2009–2013. Parkinsonism Relat Disord 2015;21:449–454.
3.
Sparrow D, DeAngelis TR, Hendron K, Thomas CA, Saint-Hilaire M, Ellis T. Highly challenging balance program reduces fall rate in Parkinson disease. J Neurol Phys Ther 2016;40:24–30.
4.
Canning CG, Sherrington C, Lord SR, et al. Exercise for falls prevention in Parkinson disease: a randomized controlled trial. Neurology 2015;84:304–312.
5.
Walton CC, Naismith SL, Lampit A, Mowszowski L, Lewis SJ. Cognitive training in Parkinson’s disease. Neurorehabil Neural Repair 2017;31:207–216.
6.
Mirelman A, Rochester L, Maidan I, et al. Addition of a non-immersive virtual reality component to treadmill training to reduce fall risk in older adults (V-TIME): a randomised controlled trial. Lancet 2016;388: 1170–1182.
7.
Maidan I, Rosenberg-Katz K, Jacob Y, Giladi N, Hausdorff JM, Mirelman A. Disparate effects of training on brain activation in Parkinson disease. Neurology 2017;89:1804–1810. Lord S, Galna B, Yarnall AJ, Coleman S, Burn D, Rochester L. Predicting first fall in newly diagnosed Parkinson’s disease: insights from a fall-naïve cohort. Mov Disord 2016;31:1829–1836. Henderson EJ, Lord SR, Brodie MA, et al. Rivastigmine for gait stability in patients with Parkinson’s disease (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 2016;15:249–258. Moreau C, Delval A, Defebvre L, et al; PARKGAIT-II study group. Methylphenidate for gait hypokinesia and freezing in patients with Parkinson’s disease undergoing subthalamic stimulation: a multicentre, parallel, randomised, placebo-controlled trial. Lancet Neurol 2012;11: 589–596.
8.
9.
10.
October 24, 2017
ª 2017 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
Virtually reducing fall risk in Parkinson disease Caroline Moreau, Brandon R. Barton and David Devos Neurology published online September 27, 2017 DOI 10.1212/WNL.0000000000004581 This information is current as of September 27, 2017 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/early/2017/09/27/WNL.0000000000 004581.full.html
Subspecialty Collections
This article, along with others on similar topics, appears in the following collection(s): All Rehabilitation http://www.neurology.org//cgi/collection/all_rehabilitation Assessment of cognitive disorders/dementia http://www.neurology.org//cgi/collection/assessment_of_cognitive_dis orders_dementia Parkinson's disease/Parkinsonism http://www.neurology.org//cgi/collection/parkinsons_disease_parkinso nism
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2017 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
