University of Groningen Objective and subjective movement symptoms in (functional) tremor Kramer, Gerrit

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University of Groningen

Objective and subjective movement symptoms in (functional) tremor

Kramer, Gerrit

DOI:

10.33612/diss.136731740

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Publication date: 2020

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Kramer, G. (2020). Objective and subjective movement symptoms in (functional) tremor. University of Groningen. https://doi.org/10.33612/diss.136731740

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CHAPTER 1

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11 Functional movement disorders (FMDs) are characterized by an impairment in explicit movement control[1,2], leading to symptoms such as tremor, myoclonus and dystonia[3]. These symptoms are due to a disturbance in brain function rather than brain structure[2,3]. They are part of a larger spectrum of functional neurological symptoms, including functional sensory symptoms and functional paralysis[4,5]. Together, functional neurological symptoms account for up to 15% of new patients attending an outpatient clinic[6]. An accurate estimation of the prevalence of FMDs is difficult due to variations in definitions and study populations, but estimates range between 2 and 20% in movement disorder clinics. The prevalence of FMDs in the general population is unknown[7,8]. Patients with an FMD have a similar loss in quality of life as other neurological patients such as patients with Parkinson’s disease[9]. Furthermore, as FMDs often affect the working-age population, they have a high economic burden[7,10].

Research on treatment strategies in FMDs is limited and often only applies to a subset of patients[7]. In general, a stepped care model is advised with the first step being a proper explanation[11]. Physiotherapy and psychotherapy can be effective, but it’s success also depends on the presence or absence of comorbid features as anxiety, depression or pain[7,12,13]. Prognosis appears to be unfavourable, especially without proper treatment. In one review, more than one-third of patients showed the same or worse symptoms at follow-up, and, in cases where symptoms improved, symptoms usually did not resolve completely[14].

Historical perspective and terminology

FMD symptoms, and functional neurological symptoms in general, have been classified differently over time[15] with each term providing information of the presumed pathophysiology of this disorder. One of the oldest, hysteria, indicates a causal relationship between the uterus and symptoms, a theory already mentioned in one of the oldest known medical text: the Kahun Papyrus (1900 BC)[16]. Another term is conversion disorder, originally coined by Sigmund Freud who proposed that unresolved psychological distress could be converted to physical symptoms[17], a theory still popular today. The term non-organic is used to describe the absence of structural damage, but can be troublesome as functional neurological symptoms often co-occur with other neurological diseases, like Parkinson’s disease[18]. Furthermore, non-organic would imply a very dualistic view of “the mind” and “the brain”, which contradicts substantial evidence of structural brain abnormalities in patients with for example, migraine, depression and FMDs[19,20].

Nowadays, it is advocated to use the term functional movement disorders due to several reasons. First, it describes the level of the problem, namely in the function of the nervous system, rather than in the structure. Second, it does not assume an (unproven) aetiology, which may hamper unbiased scientific research[15]. Third, this term is found to be most accepted by patients[21].

Pathophysiology

The pathophysiology of FMDs is thought to be multifactorial[5]. Traditionally, psychological factors were thought to play a major role. The proportion of psychiatric disorders in FMDs varies between INTRODUCTION

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studies and often a proper control group is lacking[17]. In one study, patients with an FMD had similar rates of self-reported psychiatric disorders as patients with other movement disorders[22]. Current theories of the neurobiology of FMDs use a Bayesian model with an important role for attention, symptom expectations, physical and emotional experiences and beliefs about illnesses[2]. In short, these theories propose that FMDs arise from a failure of inference that results in abnormal symptom perceptions and movements[2]. These theories are based on particular findings in patients with an FMD, for example, remission of symptoms during distraction[5] and the perception of a leg or arm being straight, even if it’s curled[23]. Recent functional magnetic resonance imaging (fMRI) findings support these theories. For example, in a study in which participants alternatively did or did not have control over a visual glove, patients with an FMD had a lack of change in brain activity patterns compared to healthy volunteers[24]. This lack of change in brain activity patterns was particularly present in the dorsolateral prefrontal cortex and pre-supplementary motor area, areas associated with sense of agency[24]. Furthermore, differences in grey matter were observed in patients with an FMD, particularly in limbic and sensorimotor areas, which are responsible for emotional and motor control[20]. These neurobiological theories point towards a complex pathophysiological model underlying FMDs. Future studies have to determine whether these neurobiological changes in FMDs represent a cause or consequence of this disease. The extent to which psychological factors play a role in FMDs remains unclear[25]. For example, one study reported a higher rate of emotional childhood abuse and a greater number of traumatic episodes in patients with an FMD compared to healthy controls and patients with focal hand dystonia[26]. However, this study also revealed that differences were usually not very large and the list of psychological variables which did not show any differences was impressive[27]. A recent study suggested that in-depth psychiatric interviews can reveal a higher rate of possible relevant life events[28]. For example, the authors detected severe life events in 56% of patients with an FMD, compared to 21% in patients with major depression; however, many patients with an FMD had no identifiable severe life events[28]. Also, other studies reported mainly similarities between patients with FMD and organic neurological disorders, for example with regard to depression, anxiety, dissociation, and personality disorders, especially when compared to patients with other movement disorders like Parkinson’s disease[22]. Currently, psychological factors are regarded as risk factors, which might lead to patients being susceptible to develop or maintain FMD symptoms[29].

Diagnosis and explanation

Traditionally, the diagnosis of FMDs was based on the presence of psychological disturbances and exclusion of other neurological disorders. Nowadays, the diagnosis requires positive criteria such as distraction, entrainment, and incongruency with other neurological disorders[7]. Table 1 lists the criteria currently required to diagnose a patient with an FMD[30]. It is worth noting that the older criterium of a presumed psychological stressor is no longer a diagnostic criterium[28]. This emphasis on positive criteria appears to lead to a reduced rate of misdiagnosis, that is, patients diagnosed with an FMD who turn out to have a different neurological disease explaining

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13 the symptoms. The misdiagnosis rate fell from 29% in the 1950s to 4% since the 1970s, which is similar to many other neurological and psychiatric disorders[31]. This decline in misdiagnosis rate preceded the widespread introduction of computed tomography, thereby suggesting that improved radiological imaging did not account for improved diagnostic accuracy[31].

Explanation is important in any disorder as a first step to treatment. In FMDs, this might be even more important, as acceptance of the diagnosis is regarded as one of the most important prognostic factors[32]. Explaining the disorder using the aforementioned positive criteria might help in the understanding and acceptance of this disorder[33]. For example, distraction can be demonstrated to patients with functional tremor (FT), a subtype of FMDs, by showing that performing a certain movement with the non-affected side can temporarily decrease tremor symptoms on the affected side. This procedure demonstrates that FMDs are a disorder of movement control, rather than damage to the nervous system.

Table 1 Diagnostic classification of functional movement disorders

Diagnostic classification Description

1. Documented Remittance with suggestion, physiotherapy,_{psychotherapy, placebos, ‘while unobserved’}

2a. Clinically established Inconsistent over time/incongruent with clinical condition + other manifestations: other ‘false’ signs, multiple somatizations, obvious psychiatric disturbance

2b. Clinically established minus other features

Unequivocal clinical features incompatible with organic disease with no features suggesting another underlying neurological or psychiatric problem

3. Laboratory-supported definite Electrophysiological evidence proving a psychogenic movement disorder (primarily in cases of psychogenic tremor and psychogenic myoclonus)

1 + 2a + 2b = clinically definite

Long-term assessment of movement disorder symptoms

The diagnosis of FMDs is typically made during a visit to the outpatient clinic, sometimes combined with additional neurophysiological testing. However, movement disorder symptoms can fluctuate over time[5,7,34] and studies on organic movement disorder symptoms, like Parkinson’s disease[34], indicate that patients can have difficulty recalling these fluctuations[35]. Therefore, long-term assessments might provide a more realistic picture of movement disorder symptoms. Also, long-term assessments are possible in the natural home environment and therefore, findings are ecologically valid. Furthermore, long-term assessments enable studies on the individual level using time-series analysis to study the influence of contributing factors to movement disorder symptoms[36].

Although scientific interest has increased in the assessment of movement disorder symptoms in general[37–39], there are still some unresolved issues. For example, movement disorder symptoms can be studied both objectively (using a transducer) and subjectively (using self-report). Often it is unknown which measure is preferable in clinical care or scientific research. Furthermore, studies on the combination of subjective and objective measures often show remarkable differences INTRODUCTION

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between both measures[40–42]. Another unresolved issue is the unknown minimum assessment time to provide reliable symptom estimates.

Only one study assessed specifically FMD symptoms in the home environment using objective and subjective assessment methods simultaneously[43]. In this study, patients with FT were monitored for five days objectively (using accelerometry) and subjectively (using self-report). Patients with FT showed a dramatic overestimation of their symptom duration: patients reported to have tremor 83.5% of the waking day, while accelerometery only recorded tremor for 3.9% of the time. Patients with other tremor types overestimated their tremor duration to a much lesser extent (58.0% vs 24.8%).

Problem definition and suggested methodology

The abovementioned study on the dramatic overestimation of tremor duration in patients with FT might suggest that patients with FMD do not suffer from the movement disorder symptoms themselves, but rather from the perception of movement disorder symptoms[43]. In other words, patients suffer mainly from subjective movement symptoms, not objective movement symptoms. This suggestion, combined with the extensive literature on a possible psychological origin of FMDs symptoms, might result in the conclusion that FMDs are mainly a psychological problem. However, the search for a possible psychological explanation of FMDs has often been unsuccessful, partly due to the heterogeneity in FMDs[29]. In a heterogeneous disorder like FMDs, classic case-control designs are not likely to solve this issue[36] and therefore studies on the individual level are necessary. The development of techniques for the long-term assessments of symptoms, and the analyses of such time series data, allows to perform such analyses.

The current thesis studied the influence of psychological factors on subjective and objective symptom levels in individual patients with an FMD. Before this issue was addressed, several studies focused on the objective and subjective assessment of movement disorder symptoms. This thesis concentrated mainly on patients with FT, as it this symptom can be studied simultaneously both subjectively and objectively.

Aim and outline of the thesis

The goal of this thesis is to study patients with FT on the objective and subjective level to (1) improve diagnosis (2) gain insight in pathophysiology (3) provide a first step in patient-specific treatment of FMD. In chapter 2, electromyography is used to differentiate between FT and other forms of tremor, which are lumped together under the term organic tremor (OrgT), by focusing on the stability of tremor generation on very short time intervals. In chapter 3, a review is provided that describes the current methods for long-term assessment of movement disorder symptoms in the home environment. This study forms a stepping-stone to the next three studies in which patients with tremor will be monitored in the home environment. Chapter 4-6 describes the findings of the TRIL-study (Tremor Registration and Internet diary in the Living environment): a cohort of 17 patients with FT and 27 with OrgT. These participants completed a 30-day study period during which they wore an accelerometry-based device, to record tremor objectively, and

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15 completed a web-based diary five times a day. Chapter 4 describes the minimal study period to objectively quantify tremor characteristics in patients with FT or OrgT. Chapter 5 investigated the association between objective and subjective tremor symptoms. Chapter 6 studied the influence of daily stress on (objective and subjective) tremor fluctuation in individual patients with FT or OrgT. In Chapter 7 a general discussion is provided along with suggestions for future research.

INTRODUCTION

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REFERENCES

1 Pareés I, Kassavetis P, Saifee TA, et al. Failure of explicit movement control in patients with functional motor symptoms. Mov Disord 2013;28:517–23. doi:10.1002/mds.25287

2 Edwards MJ, Adams RA, Brown H, et al. A Bayesian account of ‘hysteria’. Brain 2012;135:3495–512. doi:10.1093/brain/aws129 3 Stone J. Functional symptoms in neurology: THE BARE ESSENTIALS. Pract Neurol 2009;9:179–89. doi:10.1136/

jnnp.2009.177204

4 Edwards MJ, Fotopoulou A, Pareés I. Neurobiology of functional (psychogenic) movement disorders. Curr Opin Neurol 2013;26:442–7. doi:10.1097/WCO.0b013e3283633953

5 Morgante F, Edwards MJ, Espay AJ. Psychogenic movement disorders. Continuum (Minneap Minn) 2013;19:1383–96. doi:10.1212/01.CON.0000436160.41071.79; 10.1212/01.CON.0000436160.41071.79

6 Stone J, Carson A, Duncan R, et al. Who is referred to neurology clinics?—The diagnoses made in 3781 new patients. Clin Neurol Neurosurg 2010;112:747–51. doi:10.1016/j.clineuro.2010.05.011

7 Edwards MJ, Bhatia KP. Functional (psychogenic) movement disorders: merging mind and brain. Lancet Neurol 2012;11:250–60. doi:10.1016/S1474-4422(11)70310-6; 10.1016/S1474-4422(11)70310-6

8 Hallett M. Psychogenic movement disorders: a crisis for neurology. Curr Neurol Neurosci Rep 2006;6:269–71.

9 Anderson KE, Gruber-Baldini AL, Vaughan CG, et al. Impact of psychogenic movement disorders versus Parkinson’s on disability, quality of life, and psychopathology. Mov Disord 2007;22:2204–9. doi:10.1002/mds.21687

10 Bermingham SL, Cohen FRCGP A, Hague BS DRCOG JM, et al. The cost of somatisation among the working-age population in England for. Ment Health Fam Med 2010;7:71–84.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939455/pdf/MHFM-07-071.pdf

11 Stone J. Functional neurological disorders: the neurological assessment as treatment. Pract Neurol 2016;16:7–17. doi:10.1136/practneurol-2015-001241

12 Hinson VK, Weinstein S, Bernard B, et al. Single-blind clinical trial of psychotherapy for treatment of psychogenic movement disorders. Parkinsonism Relat Disord 2006;12:177–80. doi:10.1016/j.parkreldis.2005.10.006

13 Nielsen G, Ricciardi L, Demartini B, et al. Outcomes of a 5-day physiotherapy programme for functional (psychogenic) motor disorders. J Neurol 2015;262:674–81. doi:10.1007/s00415-014-7631-1

14 Gelauff J, Stone J, Edwards M, et al. The prognosis of functional (psychogenic) motor symptoms: A systematic review. J Neurol Neurosurg Psychiatry 2014;85:220–6. doi:10.1136/jnnp-2013-305321

15 Edwards MJ, Stone J, Lang AE. From psychogenic movement disorder to functional movement disorder: it’s time to change the name. Mov Disord 2014;29:849–52. doi:10.1002/mds.25562 [doi]

16 Tasca C, Rapetti M, Carta MG, et al. Women And Hysteria In The History Of Mental Health. Clin Pract Epidemiol Ment Heal 2012;8:110–9. doi:10.2174/1745017901208010110

17 Baizabal-Carvallo JF, Hallett M, Jankovic J. Pathogenesis and pathophysiology of functional (psychogenic) movement disorders. Neurobiol Dis 2019;127:32–44. doi:10.1016/j.nbd.2019.02.013

18 Wissel BD, Dwivedi AK, Merola A, et al. Functional neurological disorders in Parkinson disease. J Neurol Neurosurg Psychiatry 2018;89:566–71. doi:10.1136/jnnp-2017-317378

19 Stone J, Carson A. ‘Organic’ and ‘non-organic’: a tale of two turnips. Pract Neurol 2017;17:417–8. doi:10.1136/ practneurol-2017-001660

20 Maurer CW, LaFaver K, Limachia GS, et al. Gray matter differences in patients with functional movement disorders. Neurology 2018;91:e1870–9. doi:10.1212/WNL.0000000000006514

21 Stone J, Wojcik W, Durrance D, et al. What should we say to patients with symptoms unexplained by disease? The ‘number needed to offend’. Br Med J 2002;325:1449–50.

22 van der Hoeven RM, Broersma M, Pijnenborg GHM, et al. Functional (psychogenic) movement disorders associated with normal scores in psychological questionnaires: A case control study. J Psychosom Res 2015;79:190–4. doi:10.1016/j. jpsychores.2015.06.002

23 Stone J, Gelauff J, Carson A. A "twist in the tale" altered perception of ankle position in psychogenic dystonia. Mov Disord 2012;27:585–6. doi:10.1002/mds.24069

24 Nahab FB, Kundu P, Maurer C, et al. Impaired sense of agency in functional movement disorders: An fMRI study. PLoS One 2017;12:e0172502. doi:10.1371/journal.pone.0172502

25 Barbey A, Aybek S. Functional movement disorders. Curr Opin Neurol 2017;30:427–34. doi:10.1097/WCO.0000000000000464 26 Kranick S, Ekanayake V, Martinez V, et al. Psychopathology and psychogenic movement disorders. Mov Disord

2011;26:1844–50. doi:10.1002/mds.23830; 10.1002/mds.23830

27 Stone J, Edwards MJ. How ‘psychogenic’ are psychogenic movement disorders? Mov Disord 2011;26:1787–8. doi:10.1002/ mds.23882; 10.1002/mds.23882

28 Nicholson TR, Aybek S, Craig T, et al. Life events and escape in conversion disorder. Psychol Med 2016;46:2617–26. doi:10.1017/S0033291716000714

29 Miyasaki J. Functional movement disorders: five new things. Neurol Clin Pract 2017;:141–7.https://www. uptodate.com/contents/functional-movement-disorders?search=functional tremor&sectionRank=1&usage_ type=default&anchor=H398881631&source=machineLearning&selectedTitle=2~150&display_rank=2#H623641336 30 Gupta A, Lang AE. Psychogenic movement disorders. Curr Opin Neurol 2009;22:430–6. doi:10.1097/WCO.0b013e32832dc169

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17 31 Stone J, Smyth R, Carson A, et al. Systematic review of misdiagnosis of conversion symptoms and ‘hysteria’. Br Med J

2005;331:989–91. doi:10.1136/bmj.38628.466898.55

32 Espay AJ, Goldenhar LM, Voon V, et al. Opinions and clinical practices related to diagnosing and managing patients with psychogenic movement disorders: An international survey of movement disorder society members. Mov Disord 2009;24:1366–74. doi:10.1002/mds.22618

33 Stone J, Edwards M. Trick or treat? Showing patients with functional (psychogenic) motor symptoms their physical signs. Neurology 2012;79:282–4. doi:10.1212/WNL.0b013e31825fdf63 [doi]

34 Espay AJ, Bonato P, Nahab FB, et al. Technology in Parkinson’s disease: Challenges and opportunities. Mov Disord 2016;31:1272–82. doi:10.1002/mds.26642

35 Papapetropoulos SS. Patient Diaries As a Clinical Endpoint in Parkinson’s Disease Clinical Trials. CNS Neurosci Ther 2012;18:380–7. doi:10.1111/j.1755-5949.2011.00253.x

36 Molenaar PCM. A manifesto on psychology as idiographic science: brining the person back into scientific psychology, this time forever. Measurement 2004;2:201–18. doi:10.1207/s15366359mea0204_1

37 Godinho C, Domingos J, Cunha G, et al. A systematic review of the characteristics and validity of monitoring technologies to assess Parkinson’s disease. J Neuroeng Rehabil 2016;13:24. doi:10.1186/s12984-016-0136-7

38 Haubenberger D, Abbruzzese G, Bain PG, et al. Transducer-based evaluation of tremor. Mov Disord 2016;31:1327–36. doi:10.1002/mds.26671

39 Block VAJ, Pitsch E, Tahir P, et al. Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review. PLoS One 2016;11:e0154335. doi:10.1371/journal.pone.0154335

40 Kassavetis P, Batla A, Pareés I, et al. Joint hypermobility syndrome: A risk factor for fixed dystonia? Mov Disord 2012;27:1070– 1070. doi:10.1002/mds.25004

41 Perez Lloret S, Rossi M, Cardinali DP, et al. Actigraphic evaluation of motor fluctuations in patients with Parkinson’s disease. Int J Neurosci 2010;120:137–43. doi:10.3109/00207450903139663

42 Fisher JM, Hammerla NY, Ploetz T, et al. Unsupervised home monitoring of Parkinson’s disease motor symptoms using body-worn accelerometers. Park Relat Disord 2016;33:44–50. doi:10.1016/j.parkreldis.2016.09.009

43 Parees I, Saifee TA, Kassavetis P, et al. Believing is perceiving: mismatch between self-report and actigraphy in psychogenic tremor. Brain 2012;135:117–23. doi:10.1093/brain/awr292; 10.1093/brain/awr292

INTRODUCTION

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