Functional Movement Disorders Assessment Made Simple

Do you remember meeting your first person with a functional movement disorder and saying “what is this”? Maybe even, “did we learn this in PT school”?

[Disclaimer--if you are a person with a functional movement disorder-this blog post is tailored to PT or OT assessment--but there’s loads of good info for you, too! And educate your therapist--bring them this blog post!]

You are not alone! Functional movement disorders (FMD) is often a topic that isn’t even mentioned as part of graduate therapy education. So, when you started to see patients, you likely searched the literature and didn’t find a whole lot. Now, thanks to a growing body of literature (thank you, for the crew out of the UK and MGH in Boston), and a growing number of therapists and movement disorder neurologists, we have a great basis for understanding, assessing and working with people with FMD. We have a real passion to explore and understand FMDs and we have taught courses and done videos and shared a lot of resources to propel the profession forward. But now we wanted to create a go-to guide for you on the most up-to-date and effective assessment and treatment methods for FMD in an easy to use format.

PLEASE NOTE: This information is only a small segment of what we use in our FND course and our Brain Bytes Community. If you want to take your neuro skills to the next level, click here to learn more about our community.

We’ve also gathered all the basics into a helpful Cheat Sheet that you can download for free.

>> Grab Your Free 6 things every clinician should know about FND treatment here

Okay, here we go.

In this post we will cover:

Brief introduction to the pathophysiology of FMD

Our Assessment Pie chart

Focus on the Autonomic nervous system

Questionnaires and assessment tools that are helpful

Why understanding the Pathophysiology of FMD makes all of the difference (Don’t Skip this Part!)

Thanks to my teaching at USC, I am a neuropathology and neurophysiology nerd, and I can’t dive into any discussion of assessment without talking a little bit about the potential pathophysiology of FMD.. I say “potential” because there is still a lot to learn and discover in this field and new things are coming out every month in the field of fMRI (don’t you just love neuro for that!).

Now I’ll keep this simple here—we have a whole section on this in our FND Mini Course

Research has demonstrated that the pathology is not simple (no surprise there!) but it is clear that FMD is not just “in your head” or “faking it”.

From the current literature it appears that FMD is a complex connectivity problem of the nervous system. When we say connectivity problem, we mean a problem with the functional connections between different areas of the brain instead of a structural or pinpoint lesion in one area. There are several key areas that are now implicated in FMD and outlined in a lovely review of the neuroimaging from Sasikumar and Strafella (2021). As indicated in their summary figure below, key connecting brain regions like the right temporal-parietal junction, amygdala and insula have been found to be changed in FMD. These key regions also are associated with functions that underlie FMD such as an altered sense of self agency, impaired top down regulation and abnormal emotional processing.

Why is this important?

First, it tells us that this is a REAL connection problem. Sometimes health care providers struggle to wrap their heads around FMD as an actual connection problem. These studies bring to light the repeatable evidence that this is not “faked” or “made up” and that there are distinct areas where the connections have broken down. Importantly, the pathophysiology guides us to our assessment and treatment. For example, since we know that there is a problem with an altered sense of agency, we can direct intervention at autonomy and restoring self agency.

Now, we have summarized all of the pathophysiology pieces supported in literature in our first pie chart! Each of these areas have research support for underlying pathophysiology: motor control, sensory, psychosocial, lifestyle, autonomic and physical limitations.

FMD Assessment Part 1: listening

If you have heard me teach or talk about FMD (and many other disorders) before, you have heard me talk about our pie charts. The first pie chart that we presented above is based on the literature on pathophysiology in FMD. These main categories remain consistent through assessment and treatment. If you understand and apply the pie chart, you have it made a huge step to helping someone with FMD.

The first step is centered on the person in front of you: the person’s pie chart! Before you start jumping to conclusions about mechanisms and your understanding of FMD, you want to start with the most important step--LISTENING!

What does the person think is going on? What is THEIR personal pie chart? We have a great pie chart in our FMD workbook that we use to have the person describe what they think is happening. I have a screenshot of it here for you. We often send this ahead to people who are participating in our integrated treatment program so we can start to listen to their story and understand their beliefs about what is contributing to their disorder.

Again--this is your most important step of the assessment--listening, understanding and validating their story. As they share with you, they will give you huge clues as to the underlying factors so you can start constructing a pie chart with them together.

Once you have listened thoroughly to the person’s story, you will have a lot of clues as to where to start your assessment. Like in this figure above, you may hear clues that lead you to explore their flexibility, their autonomic nervous system, or the sensory system.

FMD Assessment Part 2: The assessment pie chart

Now we get to dive into pie chart part 2: the assessment pie (see below). You can see that visually and categorically it follows the pathophysiology of FMD, which makes sense, right? If we know through research that these areas are important in the mechanism of the disorder, we would want to test them out and create our own pie chart to fully understand the contributing factors.

So where do we begin? If we have done our job of listening, the person has directed us to the areas that are most concerning or haven’t been looked at yet.

The autonomic nervous system (ANS) often gets overlooked and we can understand that they can be a big part of pathophysiology. So, it is important to do ANS testing as part of a thorough assessment.

So—this is where we will start today:

First, there is evidence that autonomic nervous system dysfunction can contribute to FMD symptoms

• Decreased parasympathetic activity (not correlated to depression anxiety ) (Maurer et al 2016)

• C-reactive protein elevated in FND (Kozlowska et al 2019)

• HRV low and resting HR high in FND (Koslowska et al, 2015)

This is why we recommend including the following tests in your assessment of FMD

• Measuring heart rate variability (HRV). We love using the LIEF for this because it is a portable ECG, but there are many options available now (like the Polar HR straps)

• The COMPASS 31 Screening tool

• Pupillometry. We have just started looking at this as an outcome and assessment (because visual sensitivities are so common for people). We have heard good reviews on this Reflex app for this.

• Assessing the breathing pattern: is it equal diaphragm and upper chest; is it shallow breaths or long breaths, what is the respiratory rate?

• Checking response to breath. For example, do symptoms change with an extended exhale?

• Active stand test

PS--we have an awesome “how to” library of all of these tests in our FND mini course and Brain Bytes Community.

FMD Assessment Made Simple

Now, you might be looking at the assessment pie chart and thinking, “That is a lot of stuff for an evaluation, I would never get through it all.” You are absolutely right! The assessment pie chart is not meant to be a checklist of tests for you to perform. It is meant to be a dynamic process of narrowing down and changing the pie slice sizes based on the person in front of you. We have made it comprehensive so that if you find yourself in one piece of the pie, you would have a good idea of what to test. But, we know it can be overwhelming. So, let’s make it simple:

Highlight 1 key area from their story

Identify 1 key area that will respond today

And be ok with not getting it all in one session.

>> Get more in our free FND guide

Questionnaires/Tools

Finally, we wanted to provide you with some really great tools and questionnaires that we have found highly valuable in FMD. I have included some key references to the scales as well.

Patient Specific Functional Scale (PSFS) http://www.jospt.org/doi/abs/10.2519/jospt.1998.27.5.331?code=jospt-site

Hospital Anxiety and Depression Scale http://www.sciencedirect.com/science/article/pii/S002239990100296

Patient Global Impression of Change (PGIC) https://s3.amazonaws.com/chirocode-data-files/deskbook/Patient+Global+Imp+of+Change.pdf

Clinician Global Impression of Change (CGIC) http://www.sciencedirect.com/science/article/pii/S0022510X14007953

This 2020 article by Nicholson and colleagues mentions that, “self-report measures may be more clinically meaningful” for people functional neurological disorders. One way that we can make this most meaningful is to use the PSFS. It’s a great way to build rapport, trust, and patient autonomy by allowing your patient to decide which goals are most relevant to them.

Whew - We made it through FMD assessment! When I started working with people with FMD, I wasn’t sure where to start and often felt like I was all over the place before we started to put it together in a more systematic way. Now, our whole team is a part of the evaluation process in an integrated way and we have been able to get to the underlying problems more quickly and see results.

We have boiled down this approach into an easy to use guide Simply sign up here with our cheat sheet that you can use in the clinic with your patients immediately!

>> Grab Your Free FND guide here

Remember, this information is only a small segment of our FND Mini Course. If you want to take your neuro skills to the next level, click here to learn more about this powerful self paced course.

Cheers to your #iloveneuro spirit,

Dr. Julie Hershberg, PT, DPT, NCS and Jake Pham SPT

References (an extended reference list for you!)

Pathophysiology

​​Aybek S, Vuilleumier P. (2016) Imaging studies of functional neurological disorders. Handbook of Clinical Neurology; 139: 73-84.

Aybek, S., Nicholson, T. R., O’Daly, O., Zelaya, F., Kanaan, R. A., & David, A. S. (2015). Emotion-motion interactions in conversion disorder: An fMRI study. PLoS ONE, 10(4), 1–12. https://doi.org/10.1371/journal.pone.0123273

Baizabal-Carvallo, J. F., Hallett, M., & Jankovic, J. (2019). Pathogenesis and pathophysiology of functional (psychogenic) movement disorders. Neurobiology of Disease, 127, 32-44. https://doi.org/10.1016/j.nbd.2019.02.013

Buhrmann, T., & Di Paolo, E. (2017). The sense of agency–a phenomenological consequence of enacting sensorimotor schemes. Phenomenology and the Cognitive Sciences, 16(2), 207-236. https://doi.org/10.1007/s11097-015-9446-7

Centonze, D Stampanoni Bassi, M. (2021) Time for a new deal between neurology and psychoanalysis, Brain, 144(8): 2228–2230,

Cojan, Y., Waber, L., Carruzzo, A., & Vuilleumier, P. (2009). Motor inhibition in hysterical conversion paralysis. NeuroImage, 47(3), 1026–1037. https://doi.org/10.1016/j.neuroimage.2009.05.023

Dreissen, Y. E. M., Boeree, T., Koelman, J. H. T. M., & Tijssen, M. A. J. (2017). Startle responses in functional jerky movement disorders are increased but have a normal pattern. Parkinsonism & related disorders, 40, 27-32. https://doi.org/10.1016/j.parkreldis.2017.04.001

Espay, A. J., Maloney, T., Vannest, J., Norris, M. M., Eliassen, J. C., Neefus, E., … Szaflarski, J. P. (2018). Impaired emotion processing in functional (psychogenic) tremor: A functional magnetic resonance imaging study. NeuroImage: Clinical, 17, 179–187. https://doi.org/10.1016/j.nicl.2017.10.020

Edwards A.J., Bhatia KP. (2012) Functional (psychogenic) movement disorders: merging mind and brain. Lancet Neurol; 11: 25-260.

Espay, A. J., Maloney, T., Vannest, J., Norris, M. M., Eliassen, J. C., Neefus, E., … Szaflarski, J. P. (2018). Dysfunction in emotion processing underlies functional (psychogenic) dystonia. Movement Disorders, 33(1), 136–145. https://doi.org/10.1002/mds.27217

Ganos, C., Edwards, M. J., & Bhatia, K. P. (2014). The phenomenology of functional (psychogenic) dystonia. Movement disorders clinical practice, 1(1), 36-44. https://doi.org/10.1002/mdc3.12013

Hipolito, I. (2016). The phenomenology of the intersubjective impairment. Journal of evaluation in clinical practice, 22(4), 608-614. https://doi.org/10.1111/jep.12560

Hosseini, S. A., & Padhy, R. K. (2021). Body Image Distortion. In StatPearls. StatPearls Publishing

Jalilianhasanpour, R., Ospina, J. P., Williams, B., Mello, J., MacLean, J., Ranford, J., ... & Perez, D. L. (2019). Secure attachment and depression predict 6-month outcome in motor functional neurological disorders: a prospective pilot study. Psychosomatics, 60(4), 365-375. https://doi.org/10.1016/j.psym.2018.08.004.

Kozlowska K, Palmer DM, Brown KJ, McLean L, Scher S, Gevirtz R, Chudleigh C, Williams LM. Reduction of autonomic regulation in children and adolescents with conversion disorders. Psychosom Med. 2015 May;77(4):356-70. doi: 10.1097/PSY.0000000000000184. PMID: 25954919.

Maurer, C. W., LaFaver, K., Ameli, R., Epstein, S. A., Hallett, M., & Horovitz, S. G. (2016). Impaired self-agency in functional movement disorders: a resting-state fMRI study. Neurology, 87(6), 564-570.https://doi.org/10.1212/WNL.0000000000002940.

Maurer CW, Liu VD, LaFaver K, Ameli R, Wu R, Toledo R, Epstein SA, Hallett M. (2016) Impaired resting vagal tone in patients with functional movement disorders. Parkinsonism & Related Disorders, 30, 18-22.

Morgante, F. , Tinazzi, M. , Squintani, G. , Martino, D. , Defazio, G. , Romito, L. , Albanese, A. , Di Matteo, A. , Quartarone, A. , Girlanda, P. , Fiorio, M. , Berardelli, A. & (2011). Abnormal tactile temporal discrimination in psychogenic dystonia. Neurology, 77 (12), 1191-1197. doi: 10.1212/WNL.0b013e31822f0449.

Pareés, I., Kassavetis, P., Saifee, T. A., Sadnicka, A., Bhatia, K. P., Fotopoulou, A., & Edwards, M. J. (2012). ‘Jumping to conclusions’ bias in functional movement disorders. J Neurol Neurosurg Psychiatry, 83(4), 460-463. http://dx.doi.org/10.1136/jnnp-2011-300982

Pareés I, Brown H, Nuruki A, et al. (2014) Loss of sensory attenuation in patients with functional (psychogenic) movement disorders. Brain., 137(11):2916-2921. doi:10.1093/brain/awu237

Sasikumar, S, Strafella, A.P. (2021)The neuroimaging evidence of brain abnormalities in functional movement disorders, Brain, 144 (8): 2278–2283,

Sojka, P., Lošák, J., Lamoš, M., Bareš, M., Kašpárek, T., & Světlák, M. (2019). Emotion Regulation in Functional Movement Disorder: an exploratory fMRI study. Frontiers in neurology, 10, 861. https://doi.org/10.3389/fneur.2019.00861

Thenganatt, M. A., & Jankovic, J. (2019). Psychogenic (Functional) Movement Disorders. CONTINUUM: Lifelong Learning in Neurology, 25(4), 1121-1140. http://doi.org/10.1212/CON.0000000000000755

Voon, V., Brezing, C., Gallea, C., Ameli, R., Roelofs, K., Lafrance, W. C., & Hallett, M. (2010). Emotional stimuli and motor conversion disorder. Brain, 133(5), 1526–1536. https://doi.org/10.1093/brain/awq054

Diagnosis

Finkelstein SA, Cortel-LeBlanc MA, Cortel-LeBlanc A, Stone J. Functional neurological disorder in the emergency department. Academic emergency medicine. Published online 2021. doi:10.1111/acem.14263

Gasca-salas C, Lang A. (2016) Neurologic diagnostic criteria for functional neurologic disorders. Handbook of Clinical Neurology. 2016;139:193-212. doi:10.1016/B978-0-12-801772-2.00017-5

Hallett, M. (2019). Functional movement disorders: Is the crisis resolved?. Movement Disorders. 34(7). 971-974. http://doi.org/10.1002/mds.27713

Hassa, T., Sebastian, A., Liepert, J., Weiller, C., Schmidt, R., & Tüscher, O. (2017). Symptom-specific amygdala hyperactivity modulates motor control network in conversion disorder. NeuroImage: Clinical, 15, 143–150. https://doi.org/10.1016/j.nicl.2017.04.004

Park, J. E., Maurer, C. W., & Hallett, M. (2015). The “Whack‐a‐Mole” Sign in Functional Movement Disorders. Movement disorders clinical practice, 2(3), 286-288. https://doi.org/10.1002/mdc3.12177

Perez, D. L., Haller, A. L., & Espay, A. J. (2019). Should neurologists diagnose and manage functional neurologic disorders? It is complicated. Neurology: Clinical Practice, 9(2), 165-167. https://doi.org/10.1212/CPJ.0000000000000573

Popkirov, S., Hoeritzauer, I., Colvin, L., Carson, A. J., & Stone, J. (2019). Complex regional pain syndrome and functional neurological disorders–time for reconciliation. J Neurol Neurosurg Psychiatry, 90(5), 608-614. http://dx.doi.org/10.1136/jnnp-2018-318298

Roper, L. S., Saifee, T. A., Parees, I., Rickards, H., & Edwards, M. J. (2013). How to use the entrainment test in the diagnosis of functional tremor. Practical neurology, 13(6), 396-398. http://dx.doi.org/10.1136/practneurol-2013-000549

Stone, J. (2009). Functional symptoms in neurology: THE BARE ESSENTIALS. Practical Neurology, 9(3), 179–189. https://doi.org/10.1136/jnnp.2009.177204

Stone, J., Reuber, M., & Carson, A. (2013). Functional symptoms in neurology: mimics and chameleons. Practical Neurology, 13(2), 104–113. https://doi.org/10.1136/practneurol-2012-000422

Stone, J. and Hoeritzauer, I. (2019), How Do I Explain the Diagnosis of Functional Movement Disorder to a Patient?. Mov Disord Clin Pract, 6, 419-419. http://doi.org/10.1002/mdc3.12785

Treatment

Byl, N. N., Nagajaran, S., & McKenzie, A. L. (2003). Effect of sensory discrimination training on structure and function in patients with focal hand dystonia: a case series. Archives of physical medicine and rehabilitation, 84(10), 1505-1514. https://doi.org/10.1016/S0003-9993(03)00276-4

Cock HR, Edwards M. Functional neurological disorders: acute presentations and management. Clinical medicine (London, England). 2018;18(5):414-417. doi:10.7861/clinmedicine.18-5-414

Czarnecki, K., Thompson, J. M., Seime, R., Geda, Y. E., Duffy, J. R., & Ahlskog, J. E. (2012). Parkinsonism and Related Disorders Functional movement disorders : Successful treatment with a physical therapy rehabilitation protocol. Parkinsonism and Related Disorders, 18(3), 247–251. https://doi.org/10.1016/j.parkreldis.2011.10.011

Hallett, M. (2018). The most promising advances in our understanding and treatment of functional (psychogenic) movement disorders. Parkinsonism and Related Disorders, 46, S80–S82. https://doi.org/10.1016/j.parkreldis.2017.07.002

Hallett, M. (2012). Stepped care for functional neurological symptoms–a new approach to improving outcomes for a common neurological problem in Scotland. Healthcare Improvement Scotland.

Hebert C, Behel JM, Pal G, Kasi R, Kompoliti K. Multidisciplinary inpatient rehabilitation for Functional Movement Disorders: A prospective study with long term follow up. Parkinsonism Relat Disord. 2021 Jan;82:50-55. doi: 10.1016/j.parkreldis.2020.11.018. Epub 2020 Nov 21. PMID: 33248393.

Jacob, A. E., Smith, C. A., Jablonski, M. E., Roach, A. R., Kaelin, D. L., Stretz-Thurmond, D., & LaFaver, K. (2018). Multidisciplinary clinic for functional movement disorders (FMD): 1-year experience from a single centre. Journal of Neurology, Neurosurgery & Psychiatry, 89(9), 1011-1012.

Jordbru, A. A., Smedstad, L. M., Klungsøyr, O., & Martinsen, E. W. (2014). Psychogenic gait disorder: a randomized controlled trial of physical rehabilitation with one-year follow-up. Journal of rehabilitation medicine, 46(2), 181-187.https://doi.org/10.2340/16501977-1246.

Lidstone, S. C., MacGillivray, L., & Lang, A. E. (2020). Integrated therapy for functional movement disorders: time for a change. Movement disorders clinical practice, 7(2), 169-174

Nielsen, G. (2016). Physical treatment of functional neurologic disorders. Elsevier In Handbook of Clinical neurology,139,555-569. https://doi.org/10.1016/B978-0-12-801772-2.00045-X

Nielsen, G., Stone, J., Matthews, A., Brown, M., Sparkes, C., Farmer, R., … Edwards, M. (2015). Physiotherapy for functional motor disorders: A consensus recommendation. Journal of Neurology, Neurosurgery and Psychiatry, 86(10), 1113–1119. https://doi.org/10.1136/jnnp-2014-309255

Rommelfanger, K. S., Factor, S. A., LaRoche, S., Rosen, P., Young, R., & Rapaport, M. H. (2017). Disentangling stigma from functional neurological disorders: Conference report and roadmap for the future. Frontiers in Neurology, 8, 1–7. https://doi.org/10.3389/fneur.2017.00106

Wulf, G., & Lewthwaite, R. (2016). Optimizing Performance through Intrinsic Motivation and Attention for Learning: The OPTIMAL theory of motor learning. Psychonomic Bulletin & Review, 22(6), 1–35. http://doi.org/10.3758/s13423-015-0999-9

Zito, G. A., Apazoglou, K., Paraschiv-Ionescu, A., Aminian, K., & Aybek, S. (2019). Abnormal postural behavior in patients with functional movement disorders during exposure to stress. Psychoneuroendocrinology, 101, 232-239. https://doi.org/10.1016/j.psyneuen.2018.11.020

The Other Invisible FND Conditions

Ashar, Y. K., Gordon, A., Schubiner, H., Uipi, C., Knight, K., Anderson, Z., Carlisle, J., Polisky, L., Geuter, S., Flood, T. F., Kragel, P. A., Dimidjian, S., Lumley, M. A., & Wager, T. D. (2021). Effect of pain reprocessing therapy vs placebo and usual care for patients with chronic back pain. JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2021.2669

Biagianti, B., Stocchetti, N., Brambilla, P., & Van Vleet, T. (2020). Brain dysfunction underlying prolonged post-concussive syndrome: a systematic review. Journal of affective disorders, 262, 71-76.

Bowering KJ, O’Connell NE, Tabor A, et al. The effects of graded motor imagery and its components on chronic pain: a systematic review and meta-analysis. J Pain. 2013;14(1):3-13. doi:10.1016/j.jpain.2012.09.007

Collins MW, Kontos AP, Reynolds E, Murawski CD, Fu FH. (2014) A comprehensive, targeted approach to the clinical care of athletes following sport-related concussion. Knee Surgery, Sports Traumatology, Arthroscopy; 22:235-246

Edwards, M. J., & Rothwell, J. C. (2011). Losing focus: how paying attention can be bad for movement. Movement Disorders, 26(11), 1969-1970. https://doi.org/10.1002/mds.2392

Farrell G, Chapple C, Kennedy E, et al (2021). Dysfunction of the stress response in individuals with persistent post-concussion symptoms: a scoping review protocol. Physical therapy reviews. Published online 2021. doi:10.1080/10833196.2021.1948752

Gould SJ, Cochrane GD, Johnson J, Hebson CL, Kazamel M. Orthostatic intolerance in post-concussion patients. The Physician and sportsmedicine. ahead-of-print(ahead-of-print):1-6. doi:10.1080/00913847.2021.1953357

Habs, M., Strobl, R., Grill, E., Dieterich, M., & Becker-Bense, S. (2020). Primary or secondary chronic functional dizziness: does it make a difference? A DizzyReg study in 356 patients. Journal of neurology,

Holmberg JM. (2020)Pathophysiology, Differential Diagnosis, and Management of Persistent Postural-Perceptual Dizziness: A Review. Perspectives of the ASHA special interest groups. 5(1):181-191. doi:10.1044/2019_PERSP-19-00105

Korgaonkar MS, Williamson T, Bryant RA. (2021) Neural activity during response inhibition in mild traumatic brain injury and posttraumatic stress disorder. Neurobiol Stress. Feb 17;14:100308. doi: 10.1016/j.ynstr.2021.100308. PMID: 33665241; PMCID: PMC7905369.

Moseley GL, Zalucki NM, Wiech K. (2008) Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain. Pain. 137(3):600-608. doi:10.1016/j.pain.2007.10.021.

Popkirov, S., Hoeritzauer, I., Colvin, L., Carson, A. J., & Stone, J. (2019). Complex regional pain syndrome and functional neurological disorders–time for reconciliation. J Neurol Neurosurg Psychiatry, 90(5), 608-614. http://dx.doi.org/10.1136/jnnp-2018-318298

Smyth, N., Flynn, M., Rajcani, J., Hucklebridge, M. F., Thorn, L., Wood, C., ... & Clow, A. (2019). Attenuated cortisol reactivity to psychosocial stress is associated with greater visual dependency in postural control. Psychoneuroendocrinology, 104, 185-190.

Snyder A, Patel M, Sheridan C, et al. (2019) Cardiorespiratory Stress-Response in Youth with Persistent Post-Concussion Symptoms. Neurology. 93(14 Supplement 1):S15-S15. doi:10.1212/01.wnl.0000580972.52778.e2

Tapia RN, Eapen BC. Rehabilitation of Persistent Symptoms After Concussion. Physical medicine and rehabilitation clinics of North America. 2016;28(2):287-299. doi:10.1016/j.pmr.2016.12.006