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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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 3

Long-term ambulatory assessment of

motor symptoms in movement

disorders: a best-evidence review

G. Kramer, NM Maurits, JGM Rosmalen, MAJ Tijssen Basal Ganglia 14 (2018) 8–21

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ABSTRACT

Introduction: assessing movement disorders in daily life can provide information that might not be available during a short clinical visit. This review provides an overview of the currently available ambulatory registration methods to assess motor symptoms.

Methods: a systematic review was performed of ambulatory registration methods, registering motor symptoms for at least 24 hours. The following characteristics were studied: study goal, study population, data acquisition, outcome measures, and data interpretation.

Results: For the classical subjective approach, a patient-kept diary, two types are widely applied: the ON/OFF diary to assess the medication response status in patients with Parkinson’s Disease (PD), and the fall diary to assess fall frequency. Both diaries are established methods for clinical decision-making. However, both diaries have disadvantages, especially since self-report might not always agree with clinicians’ ratings. An often-used alternative objective approach that employs accelerometry can assess activity levels and gait, monitor disease progression and distinguish between healthy controls and patients. However, accelerometry cannot reliably assess medication status in PD nor distinguish between different diseases. Also due to the heterogeneity in body locations for the accelerometer and outcome measures, there are no gold standards to rely on. Accelerometry to assess tremor can be used to obtain clinically valid measures. The combination of objective and subjective measurements is, at this point, mainly useful for scientific research. Conclusion: Subjective measurements of ON/OFF status and fall frequency remain the most widely adopted long-term registration methods. Most other methods first need more validation in a clinical setting before they can be applied in patient care.

Keywords: movement disorders, motor symptoms, ambulatory registration, accelerometer, diary, continuous monitoring.

Highlights:

1. Ambulatory assessment of movement disorders can provide valuable clinical information 2. The main established methods, the ON/OFF diary and fall diary, rely on self-report 3. Subjective and objective registration methods provide different types of information 4. Most objective methods require further validation prior to routine application

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1. INTRODUCTION

Recently, there has been great interest in studying motor symptoms in movement disorders objectively[1–3]. Movement disorders can be broadly divided into two subtypes: hyperkinetic and hypokinetic movement disorders. Hypokinetic movement disorders, including Parkinson’s disease (PD), have bradykinesia as a core feature. Hyperkinetic movement disorders, for example tremor, chorea, and myoclonus, are characterized by an increase in muscle activity.

Currently, the standard method to assess movement disorders is a clinical examination during an outpatient clinic visit[4]. Clinical rating scales, such as the Unified Parkinson’s Disease Rating Scale (UPDRS), can standardize this. Such an assessment, however, only provides a snapshot of the patient’s condition. Many symptoms are only present for part of the day[4]. For example, patients with PD can exhibit response fluctuations with during parts of the day a good response to medication (ON time) and at other times no good response (OFF time), plus periods of medication-induced dyskinesias (ON with dyskinesias). Recalling such a fluctuating pattern accurately can be difficult for patients and can therefore result in an inaccurate estimate of the symptoms[5].

Monitoring patients for a longer period (hours, days) can provide a more accurate assessment of motor symptoms in daily life[4]. Moreover, increased insight into the pattern of movement-disorder symptoms during the day might help in studying factors contributing to symptom fluctuations. The classical approach for monitoring patients for a longer period is using a diary. An ON/OFF diary, for example, studies medication response in PD for a pre-specified interval[6]; a fall diary assesses the fall frequency by applying an event-related design[7]. Using measuring devices, movement disorder motor symptoms during daily life activities can be quantified objectively. Examples of measuring devices include accelerometers, measuring acceleration of a body part, and gyroscopes, measuring angular velocity. These methods can be used to study tremor, general activity, and gait patterns. Although such objective registrations have been applied for over 30 years[8], subjective measurements remain the primary assessment tools or endpoints in clinical care and research in PD[4]. However, there is growing awareness that objective measures might improve or complement subjective measures in capturing the full complexity of motor symptoms[1]. Furthermore, a recent study discovered a discrepancy between subjective and objective tremor measurements[9]. It can thus be questioned whether subjective or objective methods should be preferred, or whether they should be combined since they provide different information.

This review will provide an overview of the currently available ambulatory registration methods for motor symptoms in movement disorders. To do so, it will describe the characteristics, data acquisition, outcome measures and data interpretation of these registration methods, as well as describe the extent these registration methods have been applied scientifically and clinically.

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2. METHODS

A computerized MEDLINE search was performed on July 1, 2017, using combinations of text words and MeSH terms: Movement disorders [MeSH], movement disorders [title/abstract] ambulatory registration [MeSH] OR ((“Monitoring, Ambulatory”[Mesh] OR ambula*[tiab] OR outpatient[tiab] OR home[tiab]) AND (Movement Disorders[Mesh] OR movement disorder*[tiab] OR chorea[tiab] OR myoclonus[tiab] OR dystonia[tiab] OR Parkinson*[tiab] OR bradykinesia[tiab] OR tremor*[tiab]) AND (registration*[tiab] OR monitor*[tiab] OR detect*[tiab] OR sensor*[tiab] OR acceleromet*[tiab] OR gyroscope*[tiab] OR magnetometer[tiab] OR diary[tiab] OR diaries[tiab] OR record*[tiab] OR regist*[tiab] OR wireless*[tiab])). Furthermore, the bibliographies of the studies were examined for relevant studies not covered in the search. The following criteria were applied: (1) only studies in English were reviewed; (2) studies needed to apply continuous ambulatory registration in the home environment for 24 hours minimum, while subjects performed normal daily life activities; and (3) the studies focused on motor symptoms in movement disorders like tremor, gait disorders, myoclonus, dystonia, chorea, and bradykinesia. Ataxia was excluded since this diagnosis refers to a coordination problem rather than a hyperkinetic or hypokinetic movement disorder.

Data were extracted for the following items: (1) general information on the method, including type of device and brand; (2) study goal and symptom of interest; (3) study population, that is, number and characteristics of patients and controls; (4) data acquisition, that is, study length, part of the day with the device, bodily location of the device, and whether the device was ready to use (i.e., no further preparations necessary to begin the measuring period); (5) outcome measures; and (6) interpretation, that is, correlation of outcome parameters with a gold standard and whether the parameter measured reflected the symptom of interest.

3. RESULTS

3.1 Description of search results

In total, 1090 studies were identified. After application of the inclusion and exclusion criteria, 52 studies remained; details are in table 1. PD patients were included in all studies except one that concerned Huntington’s disease[10]. In 33 studies, PD was studied exclusively. No studies involving myoclonus or dystonia were found. In 15 studies a diary was used: 11 on ON/OFF levels in PD and four on falls. Furthermore, in 28 of the 52 studies, accelerometry was used to study activity levels (14), gait (12), or tremor (2). Finally, eight studies used a combination of a diary and accelerometry; one study used a method that did not fit in any of the categories (a gastrocnemius expansion measurement unit). In the following section, each of the methods assessing movement disorders in an ambulatory setting will be discussed separately.

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3.2 Diary – ON/OFF levels in PD

Study goal and study population: The ON/OFF diary is used to measure the medication response in PD patients. Out of the 11 studies, four tried to validate the ON/OFF diary by comparing with a reference diary[6,11] or clinicians’ ratings[12,13] and seven studied treatment effects[14–19]. All 11 studies assessed PD patients (table 1).

Data acquisition: The measuring period varied between 24 hours and four weeks. Diary use involves only waking time, by definition. In 10 studies, diaries had to be completed every 30 minutes and in one study every hour[13]. Four studies advised a training session to enhance reliability[6,12,13,19]. Seven studies mentioned the use of a paper diary; the other studies did not mention whether they used a paper or electronic diary (table 1).

Outcome measures: Four studies used diaries with the items “ON” or “OFF” medication[14,16,17,20]; the other seven also included items on dyskinesia[6,11–13,18,19,21].

Data interpretation: Four studies used a gold standard for comparison. The first used a reference diary (good and bad period items) and found a better correlation when applying the new items ON with or ON without troublesome dyskinesias instead of the previous ON without, ON with mild or ON with severe dyskinesias[11]. In the second study, good on time (on time without dyskinesia or with nontroublesome dyskinesias) most strongly correlated with the patients’ perceived duration of a good response as measured by a visual analog scale and overall motor response over the day[6]. The third and fourth studies used simultaneous clinicians’ ratings and found a correspondence of 80% and a kappa of 0.62, respectively[12,13].

Summary: The ON/OFF diary has been used extensively in PD patients. With patients reporting medication response every 30 minutes, the outcome is meaningful for clinical practice. However, patient self-report and clinicians’ ratings do not always correspond regarding the medication status of PD patients.

3.3 Diary – Falls

Study goal and study population: Fall diaries are used to study the fall frequency and circumstances. One study aimed to identify modifiable predictors of falls in patients with Alzheimer’s disease, Lewy body dementia, or vascular dementia[22]; another to assess the circumstances of falls in PD patients, patients with mild cognitive impairment, or patients with a history of idiopathic falls[7]; the third to study whether treadmill training reduced fall frequency in PD patients[23]; and the fourth to compare characteristics of community and home-based falls in PD patients[24].

Data acquisition: All studies used a long measuring period: 6, 12, or 14 months (table 1). Three studies used exclusively paper diaries[7,22,24] whereas the fourth also provided the possibility of using a web-based calendar or smartphone application. The diaries had an event-related design: patients only completed the fall diary when they fell.

Outcome measures: In two studies, patients only reported their falls[22,23], while the other two also asked the patients for fall-related characteristics[7,24].

Data interpretation: None of the studies used a gold standard to validate the fall diary. One study noted a possible difference in what patients and clinicians would consider a fall[7].

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Summary: Fall diaries are used to detect the circumstances of falls and the effect of therapy, not only in PD patients but also in other neurodegenerative diseases. However, the event-related design can limit the application in daily clinical practice, especially in patients with infrequent falls.

3.4 Accelerometer – activity levels

Study goal and study population: Accelerometry can be applied to monitor activity levels. Nine studies compared activity levels between patients with neurological disorders and healthy controls[10,25–32] and five studies investigated the correlation between clinicians’ ratings and activity levels as measured with accelerometers[33–37]. Of the 14 studies included, 10 investigated activity levels in PD patients, one in Huntington’s Disease patients[10], one in PD and dementia patients[31], one in PD, neurodegenerative ataxia, and supranuclear palsy patients[29], while the remaining study included Multiple Sclerosis, PD, and primary muscle disorder patients[25].

Data acquisition: The studies used a measuring period varying between two and seven days[25–29]. Eleven mentioned the need to remove the device before swimming and showering[10,25,38,26,31–37]; three studies additionally stated removing it before sleeping[26,34,37]. Devices were worn on the wrist in five studies[28,32,33,35,36], on the ankle in four[25,26,34,37], on the thigh in three[27,29,30], on the lower back in one[31], and on the chest in one[10]. Furthermore, in five studies, the devices were not ready to use: in two, a walking trial was required to calibrate the device[25,37]. In another, the activity monitor had to be adjusted per patient[26]. One study mentioned an in-home visit to place and remove the device[34] and the last an in-clinic visit prior to starting the data acquisition[10].

Outcome measures: Much heterogeneity was found among the different outcome measures extracted from the accelerometer data. Six studies used algorithms to detect certain predefined movements like stepping, bout length, and sit-to-stand transitions[10,29–31,34,37]. Five used algorithms to analyze qualitative characteristics of the accelerometer data, for example, movement indices and rest activity patterns[28,32,33,35,36]. The remaining studies used a combination of both approaches[25–27].

Data interpretation: In five studies, accelerometry outcome measures were correlated to the UPDRS as gold standard: three found a moderate correlation between activity levels and the UPDRS[33,34,37] and two studies found a correlation between diurnal activity measures and the UPDRS, with the exception of hypokinesia measures[35,36]. Four studies mention difficulty measuring activity levels in PD patients with response fluctuations: dyskinesias are often classified as normal activity[32,33,36,37]. Two studies stated that other medical conditions might also influence ambulatory activity[29,37], reducing its usefulness to distinguish between movement disorders. One study highlighted the heterogeneity of activity outcomes among different algorithms used in the analyses and concluded that there are no gold measures to rely on[33].

Summary: Accelerometry is used in PD, primary muscle disorder, Multiple Sclerosis, and Huntington’s disease. These devices often require some form of preparation prior to initial use. The variability in body locations for the device and in outcome parameters complicate routine application in daily clinical practice. Moreover, in PD, dyskinesias can be incorrectly classified as

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43 normal activity. Furthermore, reduced activity levels can be caused by other medical conditions as well, therefore, limiting the use in daily clinical practice.

3.5 Accelerometer – gait

Study goal and study population: Accelerometry can also be applied to study gait patterns. This can be used to identify disease-specific gait abnormalities[39–47] or to study the treatment effects[48–50]. Of the 12 studies included, one studied PD patients, vascular-parkinsonism patients and healthy controls; one studied PD patients, patients with mild cognitive impairment or dementia and healthy controls; and 10 studied PD patients (table 1). Four of these 10 studies also included healthy controls.

Data acquisition: Study length varied between one and seven days (table 1). The device was worn on the back in four studies[42,44,45,47], around the waist/belt in five[39,41,43,46,50], around the thigh in one[48], around the ankle in one[49], and around the waist and limbs in one[40]. One study mentioned the need for a walking trial to adjust the measuring device[40] and another study mentioned a technician’s home visit to place and remove patient’s device[48]. Three studies mentioned the device was removed before sleeping[40,44,45], and two stated removal during water activities[42,43]. Four other studies reported continuous wearing[41,49–51].

Outcome measures: Considerable heterogeneity existed in the outcome measures used: turning characteristics[40,44], walking time and step-to-step variability[42], missteps[45], freezing of gait[47], gait cycle and gait acceleration[39,41,50], volume and pattern of ambulatory activity[48], cadence and variability in walking pattern[47], amount of overall movements per 24 hours and gait acceleration[43], and dyskinesia[49].

Data interpretation: Seven studies correlated the outcome of accelerometer data analysis with a gold standard. In four, a laboratory-based video analysis was used to develop algorithms to detect turning characteristics[40,44], missteps[45] and medication-induced dyskinesia[49]. In all four studies, significant differences were found between patients and controls during the ambulant measuring period. The three other studies used the New Freezing Of Gait Questionnaire[46], UPDRS[41], and clinical parameters as Hoehn & Yahr stage for PD[48], but did not find a correlation of any of these standards with the accelerometer data. One study mentioned missteps in a laboratory might be different than missteps in real life and therefore, their algorithm could only detect possible and not definite missteps[45]. In another study, dyskinesias were erroneously detected in non-dyskinetic legs[49]. Comparable disturbances in generating voluntary movements were found in vascular parkinsonism and PD[43].

Summary: Accelerometry to study gait patters has been used in PD and vascular parkinsonism patients. The device was worn on various body locations with different studies using different outcome parameters. In some studies, accelerometry enabled to distinguish between healthy controls and affected patients, while in others, accelerometry outcome did not correlate with subjective rating scales.

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3.6 Accelerometer – tremor

Study goal and study population: Tremor can be measured by accelerometry due to its characteristic rhythmic oscillatory pattern. One study analyzed the effect of thalamotomy on tremor due to PD, essential tremor, trauma capitis and stroke[52]. The other developed a new tremor-detection algorithm in PD patients[53].

Data acquisition: Subjects were monitored for 24 hours[52] or six days[53] with a wrist-worn accelerometer. The device was removed for sports and showering[52] or worn continuously[53].

Outcome measures: Accelerometry was used to measure the proportion of time with tremor. One study referred to a pilot study in which a tremor-detection algorithm was developed[52], while the other study used a laboratory video analysis[53].

Data interpretation: Both studies found a good correlation between the proportion of time with tremor and the UPDRS-III (motor examination), although some activities might resemble tremor, like knitting[52,53].

Summary: Applied to various tremor types, accelerometry could be used to evaluate the effect of thalamotomy. Accelerometry recordings correlated with subjective rating scales, although accelerometry might also erroneously classify physiological activity as tremor.

3.7 Combination of methods

Study goal and study population: Eight studies were found that combined registration methods. All used a diary and an accelerometer: two used an accelerometer to detect gait features that predicted fall risk as scored using a fall diary[46,54], four used an accelerometer to detect ON/OFF periods, comparing this with a diary[38,55–57], and two compared subjective diary and objective accelerometer estimates of percentage of tremor time[9,58]. The studies on falls and gait features included PD patients exclusively[51,54]. One of the studies focusing on ON/OFF periods and accelerometry included both PD patients and healthy controls[55]; the others studied PD patients exclusively[38,56,57]. One study on tremor focused on patients with PD[58], while the other also included psychogenic (functional) tremor, dystonic tremor, and tremor due to Wilson’s disease[9].

Data acquisition: The studies on falls and gait features both used a longer period to detect fall frequency (one year) and a shorter period for accelerometry recordings: three[51] or seven days[54] to detect any gait abnormalities predictive for falls. The accelerometer was worn on the upper thigh[54], or lower back[51].

Studies on ON/OFF periods and accelerometry used a 72-hour[55], four-day[38] or seven-day period[38,56] to compare both methods. Accelerometers were worn on the non-dominant wrist[55], both wrists[56], triceps[57] or on the waist and all the limbs[38]. Finally, the studies on subjective and objective tremor measurements used a five [9] or three-day [58] period and the device was worn on the wrist[9,58]. Four studies reported the device could not be worn while swimming or showering[9,38,46,58]. Two studies on accelerometry and ON/OFF diary mentioned a training session for the ON/OFF diary prior to the study’s start[55,56]. In a study on ON/OFF periods and accelerometry, patients were interviewed beforehand to gather disease state information to guide the feature selection process included in analyzing accelerometry data[38]. One study mentioned instruction on the first measuring day[58].

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45 Outcome measures: Two studies focused on predictability of accelerometry-derived features for fall risk[51,54]. One study focused on postures, walking, and number of steps[54], while the other analyzed total number of activity bouts, total percentage of activity duration, median number of steps per bout, median activity, and activity bout duration[51]. Three studies used accelerometry and an ON/OFF diary to assess activity levels in ON/OFF/Dyskinesia periods[55–57], while the fourth study used accelerometry and a patient kept symptom log – which was designed for this specific study – to study ON/OFF periods. Two studies used the results of accelerometry and a diary to compare subjective and objective symptom assessment; both used the percentage of time with tremor[9,58].

Data interpretation: In both studies assessing fall risk by means of accelerometry, the fall diary was used as gold standard to assess fall frequency and the accelerometry data was compared with UPDRS[51,54]. In one study, accelerometer data could not identify recurrent fallers, while the UPDRS could[54]. In the other study, accelerometry data could predict the time to the first fall, while the UPDRS could not[51]. Two studies comparing accelerometry with the ON/OFF diary first performed a pilot study with clinicians’ ratings to validate the accelerometry[55,56]. In the subsequent main study, no correlation was found between the ON/OFF diary and accelerometry, consistent with a third study[57]. Only in the fourth study the investigators were able to use accelerometry to identify ON/OFF periods, as registered in a patient-completed symptom log[38]. In both tremor studies, no gold standard was used and only a reference regarding the validity of the accelerometry was made[9,58]. Subjective and objective tremor scores in patients with a tremor did correlate in one study[58]. In another, this was dependent on tremor type, since a mismatch was found between subjective and objective ratings in patients with a functional tremor[9].

Summary: Using accelerometry, fall risk was predictable in PD patients in one study but not in a second study. Most studies focusing on gait-derived accelerometry features and ON/OFF fluctuations could not find a correlation between these parameters. The study that was able to identify ON/OFF periods used five accelerometers (waist and limbs) and an interview beforehand to guide analysis of accelerometer data[38]. The studies comparing diary and accelerometry tremor scores found a correlation between subjective and objective scores, with a mismatch in patients with a functional tremor.

3.8 Miscellaneous

Gastrocnemius expansion measurement unit

The gastrocnemius expansion measurement unit was studied in six PD patients[59]. The device was worn for 25 days from morning until evening. The study did not mention whether the device was ready to use. The device measured the expansion of the gastrocnemius muscle with a force-sensing resistor, with one expansion reflecting two steps. The study did not include a comparison with a gold standard to validate this method, nor did the study examine whether the parameter “expansion of the gastrocnemius muscle” reflected motion activity in PD patients.

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DISCUSSION

This review provides an overview of subjective and objective methods available for long term (>24 hours) ambulatory assessment of movement disorders. Currently, subjective measurements remain the main ambulatory registration methods in clinical practice and research. The objective approach has interesting outcomes, however, due to its heterogeneity, it is difficult to determine whether they should be preferred above subjective ones. Only accelerometry assessed tremor seems to obtain clinically valid results. The combination of subjective and objective approaches shows remarkable differences between both approaches, therefore, a better understanding is necessary on which information is provided by subjective and objective measurements.

The classical clinical subjective approach with the ON/OFF and fall diary has commonly been used as endpoint in clinical-decision making, but the design has some disadvantages. As for the ON/OFF diary, clinicians and patients can disagree on a patients functional medication state, that is, whether PD symptoms respond to medication at a specific moment[6,13]. This discrepancy might diminish if patients would receive a training session to improve the understanding of their medication state[6,12,13,19]. It is, however, questionable whether a live training session is feasible in daily clinical practice. Improvement of the scoring by patients might benefit from adequate patient information, such as a website with instruction videos. As for fall diaries, it is unknown whether the fall diary provides an accurate estimate of fall frequency, as a gold standard is missing. Besides this, the extensive measuring period prevents routine application in daily life.

The alternative (objective) approach currently mainly focuses on accelerometry to study activity levels, gait patterns and tremor. Accelerometry can be used to monitor disease progression and distinguish between healthy controls and patients[10,25–28,41,43,45]. One practical application of accelerometry is to identify fall risk in PD patients among patients who reported no falls so far[51]. Good results have also been described in detection of different tremor types in daily life[52,53]. Unfortunately, the objective measurements also have disadvantages and limitations. They often fail to measure medication response in PD[32,35,36,55–57]. Furthermore, it is difficult to distinguish between different diseases, as was illustrated in a study with comparable disturbances in patients with PD and vascular parkinsonism[43]. It is also difficult to measure medication response in PD as dyskinesia might resemble normal activity in advanced PD[33], thereby indicating the need of disease stage-specific algorithms. Finally, the considerable heterogeneity in body locations for the device and outcome parameters make it difficult to apply accelerometry in daily clinical practice, as there is no gold standard to rely on[33].The combination of subjective and objective methods is mainly used in determining whether the objective measurement (accelerometry) performs similar to the subjective measurement (diary). Many studies could not correlate subjective and objective assessments, for example in assessing ON/OFF periods in PD[55–57]. Factors influencing these results are that patients might misinterpret their symptoms or medication state[12,13] and can overestimate their symptom duration, as was evident from a study on functional and organic tremor[9]. Future research should therefore take both objective and subjective measures into account to determine which method should be preferred and is clinically most relevant.

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47 This review has some limitations. As we only included studies measuring patients for more than 24 hours, we inevitably might have missed some new devices which have not yet been studied extensively in daily life. This is also reflected in the fact that older (mainly subjective) measurements are more widespread and accepted than the newer (mainly objective) measurements. It will take years for a new method to become validated and applicable in daily clinical practice.

In conclusion, the classical subjective approach to measure movement disorders symptoms in daily life currently remains the main application in clinical practice. The alternative, objective, approach is able to detect tremor, but so far fails to assess medication response in PD and to distinguish between different movement disorders. Future studies should develop disease stage-specific algorithms and validate these in a clinical setting before this objective approach can be routinely applied in daily clinical practice.

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51 Table 1: Stu di es e xaminin g ambulatory assessm en t o f m ovem en t disor ders f or m or e than 24 h ours Au thor (y ea r) [c ita tio n] D ev ic e (b ra nd) St ud y g oa l a nd sy m pt om o f in te re st Pa tien ts typ e (n =) Co nt ro l ty pe (n =) Pa rt o f t he da y w ith de vi ce Re ad y t o use M ea su re m en t p er iod Bo dy loc a tio n O ut co me me as ure s Cor re la tion wi th go ld st and ar d M ea su re d pa ra m et er r efl ec ts sy m pt om o f in te re st O N /O FF di ar ies G ro ss et ( 20 13 ) [14 ] O N /O FF d ia ry (p ap er ) Eff ec t o f a po -m or ph in e o n P D sy m pto m s Ap om or phin e gr oup : 40 P D p at ie nt s Pl ace bo gr ou p: 1 5 P D pa tie nt s - 2-4 w ee ks NA O N /O FF t im e -H au se r ( 20 00 ) [11 ] 2 O N /O FF di ar ie s ( pap er ) D ia ry d ev el -op m en t t o as se ss m ed ic at io n re sp on se flu ct u-at io ns D ia ry 1 : 2 4 P D pa tie nt s D ia ry 2 : 1 7 P D pa tie nt s N one -24 h NA D ia ry 1 : O FF /O N wi th /wi thout m ild / se ve re d ys ki ne sia . D ia ry 2 : O FF /O N wi th /wi thout tr ou -ble som e d ys ki ne sia Re fer en ce d iar y usi ng “ go od ” a nd “b ad ” t im e: b et te r co rre lat io n w ith di ar y 2 . -H au se r ( 20 04 ) [6 ] O N /O FF d ia ry (p ap er ) D ev elopm en t of an O N /O FF d ia ry . 30 2 P D p at ie nt s N one W ak in g t im e Tr ainin g ses sio n 2x 3 d ay s NA As le ep, O FF , ON wi thout dy sk in esi a, O N w ith non trou ble som e dy sk in esi a a nd O N wi th tr ou ble som e dy sk in es ia Vi su al a na lo g s ca le s to fi ve q ue st io ns r e-ga rd in g d ys ki ne sia an d o ve ra ll m ot or re sp on se Pat ie nt s c an re ga rd th eir dy sk in esi as a s n ot se ve re d ue t o t he vi de o e xa m ple H au se r ( 20 06 ) [13 ] O N /O FF d ia ry (p ap er ) D ev elopm en t of th e O N /O FF d ia ry 50 P D p at ie nt s w ith d ys kin es ias N one H our ly in ter val w hi le a w ake Fa ce -to -fa ce in te rv ie ws 24 hou rs NA As le ep , O FF , O N w ith d ys ki ne sia an d ON wi thout dy sk in es ia . Cl ini ci an ra tin g: 80 % c or re sp on d-en ce In ac cu rat e com ple tion of th e d ia ry w as m ai nl y d ue p oo r und er sta nd in g of t he f un ct io na l st at es o f P D . Ki eb ur tz (19 97 ) [ 16 ] O N /O FF d ia ry (p ap er ) Eff ec t o f e nt a-ca po ne o n P D sy m pto m s En ta ca po ne gr ou p: 1 03 P D pat ie nt s Pl ace bo gr ou p: 1 02 PD p at ie nt s W hi le a w ake -4 x 3 d ay s NA O N /O FF ti m e -Le es ( 20 17 ) [19 ] O N /O FF d ia ry (p ap er ) Eff ec t o f opi ca pon e on P D sy m pto m s 25 m g/ d: 1 25 P D pa tie nt s. 50 m g/ d: 1 47 P D pa tie nt s. Pl ace bo gr ou p: 1 35 PD p at ie nt s Ev er y 3 0 m inu te s Tr ainin g ses sio n Th re e co n-se cut iv e d ays be fo re ea ch vis it NA O FF , O N w ith trou ble som e dy sk in esi a, O N w ith non trou ble som e dy sk in esi a, O N wi thout d ys ki ne sia , or a sle ep Re fe re nc e i s m ad e to H aus er a nd c ol -le ag ue s r eg ar di ng va lid at io n ( 2) . - Le W itt ( 20 08 ) [15 ] O N /O FF d ia ry (p ap er ) Eff ec t o f i st ra -de fy lin e o n P D sy m pto m s Istr ad ef yl in e gr ou p: 1 14 P D pa tie nt s Pl ace bo gr ou p: 5 8 P D pa tie nt s D ur in g w ak in g day Re ad y t o u se 5 t im es 2 con se cut iv e day s NA Ch ange fr om ba se lin e t o e nd po in t i n p er ce nt ag e da ily O FF t im e Re fe re nc e i s m ad e to H aus er a nd c ol -le ag ue s r eg ar di ng va lid at io n ( 3)

-3

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52 Re im er ( 20 03 ) [12 ] CA PS IT -P D O N /O FF d ia ry (p ap er ) Exp lor at ion a nd us e o f t he O N /O FF di ar y 26 P D p at ie nt s N one Ev er y 3 0 m inu te s Tr ainin g ses sio n 4 w ee ks NA O N /O FF ti m e Si m ul tan eo us ly cl in ic al a nd p at ie nt rat in g O N /O FF sc or es f or 4 h ou rs (a gr eem en t k = 0. 62 , wei gh te d k = 0. 84) -Ri nn e ( 19 98 ) [17 ] O N /O FF D ia ry (ty pe u nk no w n) Eff ec t o f e nt a-ca po ne o n P D sy m pto m s En ta ca po ne gr ou p: 7 7 P D pa tie nt s Pl ace bo gr ou p: 7 5 P D pa tie nt s -7 x 3 d ay s NA O N /O FF ti m e Re fer en ce to e ar lier st ud y r eg ar di ng val id ity . “P D p at ie nt s a re co gn iz an t o f th e b en efi ci al du rat io n o f a le vo dop a do se .” Sc hle singe r (20 14 ) [ 20 ] O N /O FF d ia ry (u nk no w n t yp e) Eff ec t o f r el ax at io n gu id ed ima ger y on PD sy m pto m s 19 P D p at ie nt s N one To ta l w ak in g tim e Re ad y t o u se 2x 3 day s NA O N /O FF -Ver ha gen M et m an (2 015 ) [ 18 ] O N /O FF d ia ry (p ap er ) Eff ec t o f le vo -c ar bi dop a in te st in al g el o n PD sy m pto m s 34 P D p at ie nt s N one -Th re e con se cut iv e da ys b ef or e an d d ur in g trea tm en t. NA OF F/ ON /ON wi th dy sk in esi a ( ev er y 3 0 m inu te s) Re fe re nc e i s m ad e to H aus er a nd c ol -le ag ue s r eg ar di ng va lid at io n ( 3) -Fal l d ia rie s Al la n ( 20 09 ) [2 2] Fal l d iar y ( pap er ) Ide nt ify ing m od ifi ab le f ac to rs of fa lls . Al zh ei m er ’s di se as e ( 38 ), va scu lar d em en tia (3 2) , L ew y b od ie s de m en tia ( 30 ) a nd PD d em en tia ( 40 ) 39 h ea lth y co nt ro ls NA -12 m on th s NA N umb er o f f al ls. -As hb ur n (2 00 8) [ 7] Fal l d iar y ( pap er ) Ide nt ify ing cir cum st an ce s of fa lls . 13 5 P D p at ie nt s N one NA -6 m on th s NA Fa lls , lo cat io n, fa ll-re lat ed a ct iv ity , pe rc ei ve d c au se , la nd in g a nd c on se -que nc es -Pat ie nt s a nd cl ini ci an s m igh t di sa gr ee o n clas -sif yi ng a n e ve nt as a f al l. La m on t ( 20 17 ) [24 ] Fal l d iar y ( pap er ) or te le phon e hot lin e Ch ar ac te ris tic s o f co mm un ity an d hom e-ba se d f al ls 19 6 P D p at ie nt s NA NA -14 m on th s NA Fa lls a nd f al l-r el at ed ev en ts ( in do or , out do or , o cc ur ring of f re ez in g o f g ai t an d en vi ro nm en tal ch al le nge s). -Fa lls c an a lso oc cu r d ue t o com or bi d c on di -tio ns . M ire lm an (2 016 ) [ 23 ] Fal l d iar y (p ap er , w eb ba se d-cal en dar or sm ar tp hon e ap pl ic at io n) Eff ec t o f t re ad m ill tra in in g + V R o n nu mb er o f f al ls. 14 6 t rea dm ill tra in in g + V R: pat ie nt s w ith P D (6 6) , m ild c og ni tiv e im pa irm en t ( 23 ) o r id io pat hi c f al ls ( 57 ) 13 6 t rea dm ill tra inin g: pat ie nt s w ith PD ( 64 ), m ild co gni tiv e im -pa irm en t ( 20 ) or i di op at hi c fa lls (5 2) NA -6 m on th s NA “a n u ne xp ec te d ev en t i n w hi ch th e p ar tic ip an t co m es t o r es t o n th e g ro un d, fl oo r o r lo w er lev el ”

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53 Ac tiv it y An dr zj ew es ki (2 01 6) [1 0] Ac ce le ro m et er (P AMS ys -X ™) Ac tiv ity 15 p at ie nt s w ith H un ting ton ’s di se ase 5 h ea lth y co nt ro ls N ot d ur in g bat hi ng , opt io na l du rin g sle ep. In -cl ini c v isi t be fo re s tu dy st ar t 6 d ay s Ch es t Ph ysi ca l a ct iv ity m eas ur es , in cl ud in g tim e s pe nt si tt in g, st an di ng , w al ki ng , an d r un ni ng , t he to ta l n um be r a nd du rat io n o f si t-t o-st an d, n um be r o f st ep s a nd w al ki ng epi so de s -Bu ss e ( 20 04 ) [2 5] St ep a ct iv ity m on ito r ( St ep Wa tc h, C am y-te ch) Ac tiv ity m on itor -in g i n n eur ol og i-ca l p at ie nt s. Fi rs t s am pl e: 1 0 am bul an t n eu ro -lo gi ca l p at ie nt s. Se co nd s am pl e: 10 M S, 1 0 P D a nd 10 p rim ar y m us cl e di so rd er p at ien ts Fi rs t s am pl e: 10 h ea lth y su bj ec ts . s ec -on d s am pl e: 30 h ea lth y su bj ec ts O nl y r em ov ed du rin g b at hin g Te st t ria l ne ce ss ar y o f 30 ste ps . 7 d ay s Ri gh t l ow er lim b a bo ve lat er al mal le ol us St ep c ou nt , a ct iv ity le ve l, p at te rn s o f ac tiv ity a nd r es t. H ei gh t, c ad en ce an d gai t s pe ed - -Ca vana ugh (2 012 ) [ 26 ] St ep m on ito r (S te pWa tc h 3 ) M on itor ing a ct iv i-ty d ec lin e i n P D . 32 P D p at ie nt s Sa m e p at ie nt gr ou p a y ea r la te r. D ur in g w ak in g hou rs , no t w hil e b at hin g, sho w er ing , or sw im m in g Ad ju st m en t of t he d ev ic e pe r p at ie nt 7 d ay s at bas el in e an d 7 d ay s at 1 y ea r fo llow -u p An kl e M ea n d ai ly s te ps , in te nsi ty ( pe ak ac tiv ity i nd ex , m od er ate -in te ns ity m inu te s, m ax imu m out put ) - O nl y m ea su rin g of a nk le a ct iv ity , th ere fo re , u ns ui t-ab le t o e xa m in e th e t im e s pe nt in v ar ie d b od y po sit io ns Ce rff (20 17 ) [3 0] Tr ia xa l ac ce ler om et er (D yn aPo rt ) hom e-ba se d ph ys ic al b eh av io r 48 P D p at ie nt s N one Ta ki ng o f t he de vi ce d ur in g w at er -ass oci at -ed t as ks -Pr oto co l: 3 da ys . O ut -co m e: m ea n 2 day s. Lo w er b ac k N um be r o f s ed -en tar y bout s, s ede nt ar y bout le ng th -G ar ci a R ui z (2 00 8) [3 3] Ac tigr ap hy (Ac tiT ra c) Ac tiv ity l ev el s in PD 28 P D p at ie nt s N one O nl y r em ov ed w he n t ak in g a bat h. -72h W ris t ( m os t aff ec ted si de ) av er ag e a ct iv ity p er ep oc h ( m G) e po ch : 2/m in Re as on ab le c or re la -tio n w ith U PD RS ( r: − 0 .5 3) a nd m ot or U PD RS ( r:− 0 .4 6 D iffi cu lt t o d is-tin gu ish n or mal m ov em en t f ro m m ed ic at io n-re lat -ed d ys ki ne sia s i n ad va nc ed P D . G od fre y ( 20 16 ) [3 0] Un i-a xi al ac ce ler om et er (a cti vP AL TM ) St ep c ou nt a nd bout de te ct ion in PD 8 P D p at ie nt s N one O nl y r em ov ed du rin g b at hin g -55 d ay s f or 8 pa rt ic ip an ts Thi gh Bout le ng th , s te p cou nt , b out c ou nt . -La ck o f w el l-d e-fin ed a lgor ith m s in l ite rat ur e c au s-es h et er og en ei ty in quan tif yi ng am bu lat or y ac tiv ity

3

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54 Va n H ilt en (19 93 ) [ 32 ] Ac tiv ity m on ito r (C H 86 34 ) M eas ur in g re sp on se flu ct ua -tio ns i n P D 15 P D p at ie nt s 10 h ea lth y co nt ro ls O nl y r em ov ed w he n t ak in g a bat h -6 d ay s N on dom i-nan t w ris t Ac tiv ity l ev el, m ov em en t i nd ex , tra ns itio n i nd ic es -N o d isc rim in at io n be tw ee n t re m or , dy sk in esi as a nd vo lit io na l m ove -m en ts . Van Hi lte n (19 93 ) [ 36 ] Ac tiv ity m on ito r (C H 86 34 ) Co mp ar in g ac tiv ity m on itor m ea su re s a nd cl ini ca l s co re s in P D. 69 P D p at ie nt s 59 h ea lth y co nt ro ls O nl y r em ov ed w he n t ak in g a bat h - 5-6 d ay s N on dom i-nan t w ris t M ov em en t i nd ex , du rat io n o f i m m o-bi lit y p er io ds Ac cor de nc e wi th U PD RS M ot or a ct iv ity m ea su re s a re u n-su ita bl e t o a ss es s dy sk in es ias . Va n H ilt en (19 98 ) [ 35 ] Ac tiv ity m on ito r (C H 86 34 ) M eas ur in g hy po ki ne sia us in g ac tigr ap hy 41 P D p at ie nt s 24 h ea lth y co nt ro ls O nl y r em ov ed w he n t ak in g a bat h -5 d ay s N on dom i-nan t w ris t M ov em en t i nd ex , du rat io n o f i m m o-bi lit y p er io ds N o si gn ifi ca nt c or -re lat io n w ith U PD RS m oto r s co re . -Kl en k ( 20 16 ) [2 9] Th re e-ax ia l Ac ce le ro m et er (a ct ivP AL 3) Am bu lat or y a c-tiv ity l ev el s a cr os s neur od eg en er a-tiv e d ise ase s Pat ie nt s w ith neur od eg en er a-tiv e at ax ia s ( 34 ), sup ra nu cl ear p al sy (1 5) , a nd P D ( 16 ) 18 h ea lth y yo un g a du lts an d 38 he al th y o ld er adu lts O nl y d ay s w ith 24 h o f m ea s-ur em en t w er e in cl ud ed -7 d ay s ( fir st an d l as t d ay ex cl ud ed i n th e ana ly sis ) Thi gh Av er ag e d ai ly w al ki ng d ur at io n, nu m be r o f s te ps , st ep s p er m in ut e, bout le ng th , nu m be r o f w al ki ng bo ut s a nd n um be r of d ai ly si t-t o-st an d tran sfe rs . -Re du ce d a ct iv ity in al l n eur od e-gen er at iv e d is-or de rs . Lo rd (2 01 3) [27 ] Ac tiv ity m on itor (P AL TMI) Am bu lat or y ac tiv ity i n P D 89 P D p at ie nt s 97 h ea lth y co nt ro ls Un kn ow n -7 d ay s Up pe r t hi gh Vo lu m e o f w al ki ng (to ta l b ou ts o r st ep s), p at te rn a nd va ria bi lit y -Bri ef sta nd in g pe rio ds a re unc or re ct ly class ifi ed as th e en d o f a w al ki ng pe rio d. N iw a ( 20 11 ) [2 8] Ac tig ra ph (M ini -m ot io n-lo ge r) M eas ur in g ci rc ad i-an r hy th m o f r es t ac tiv ity i n P D 27 P D p at ie nt s 30 h ea lth y co nt ro ls Con tin uou sly -7 d ay s Wr ist Re st a ct iv ity pa tte rn N eg at iv e c or re la -tio n w ith U PD RS pa rt 3 -Sk id m ore (2 00 8) [3 4] St ep a ct iv ity m on itor (C YMA ) M ea su ring hom e ac tiv ity lev el s in PD 26 P D p at ie nt s N one Re mo ve d du rin g b at hin g an d s le epi ng H om e v isi t to p la ce 48h Ri gh t l at er al mal le ol us To ta l n um be r o f st ep s p er d ay a nd m ax im um s te ps tak en p er h our Co rre lat io n w ith U PD RS M ot or fl uc tu -at io ns w ith in in di vi du al p a-tie nt s m ig ht a lte r m ea sur em en ts . Xa nt hop ou lo s (2 00 8) [37 ] St ep m on ito r (C YM A) Re lat io ns hi p be tw ee n m ot or pla nnin g a nd am bu lat or y per sis ten ce . 20 P D p at ie nt s N one Re mo ve d du rin g b at hin g an d s le epi ng Ca lib rat io n pe r p at ie nt 2 d ay s Ri gh t l at er al mal le ol us Am bu lat or y p er -sis te nc e ( av er ag e le ng th of w al ki ng bout s) U PD RS A D L s ca le (R =-0. 81) O th er m ed ic al co nd iti on s m ig ht in flu en ce a mb ul a-to ry p er sis ten ce

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55 G ait _El-Goh ar y (2 013 ) [ 44 ] Tr ia xia l ac ce ler om et er s, gy ro sc op es a nd ma gn et om et er s (O pal in er tial se ns or) PD : t ur nin g 12 P D p at ie nt s 18 h ea lth y co nt ro ls Al l d ay , r e-ch ar gin g e ach ni gh t. Ex pl an at io n on t he fi rs t da y. Se ve n d ay s Lu mb ar sp in e Tu rn d et ec tio n algor ith m : f re -qu en cy , d ur at io n, nu m be r o f s te ps t o co m pl et e a t ur n. Va lid at io n a ga in st m ot io n a na ly sis sy st em ( se nsi tiv ity 0, 9 s pe ci fic ity 0 ,7 5) an d t w o v id eo rat er s ( se nsi tiv ity 0, 77 /0 ,7 5 s pe ci fic ity 0, 69/ 0, 60 ). -H er m an ( 20 14 ) [42 ] Tr ia xa l ac ce ler om et er (D yn ap or t) G ai t an d b al an ce 11 0 P D p at ie nt s N one Ex ce pt du rin g ac tiv iti es l ike sho w er ing -3 d ay s Lo w er b ac k To ta l w al ki ng tim e, st ep -to -s te p va ria bi lit y -Ilu z ( 20 14 ) [ 45 ] Tr ia xa l ac ce ler om et er (D yn ap or t) Fal ls/ m iss tep s 40 P D p at ie nt s N one Re mo ve d du ring sle epi ng an d s ho we rin g -3 d ay s Lo w er b ac k M iss te ps (a lgor ith m de ve lop ed in la bor at or y) La bo rat or y e st ab -lis he d a lgor ith m : 93 .1% h it r at io a nd 98 .6 % sp ec ific ity . O nl y s us pe ct ed m iss te ps c an b e id en tifie d. M an cini (2 01 5) [4 0] Ac cl er om et er s an d g yro c-sc op es ( O pa l in er tial sen so r) Tu rnin g in P D 13 P D p at ie nt s 8 h ea lth y co nt ro ls Re ch ar gin g ev er y n ig ht In st ruc tion an d w al ki ng tria l 7 d ay s Be lt a nd o ne on e ac h f oo t Inc lu de d a ve ra ge an d c oe ffi ci en t o f va riat io n ( CV ) o f: 1) n um be r o f t ur ns pe r h ou r, 2 ) t ur n an gl e am pl itu de , 3) t ur n d ur at io n, 4 ) tu rn m ea n v el oc ity , an d 5 ) n um be r o f st ep s p er tur n. N o si gn ifi ca nt di ffer en ce s d ur in g ob se rv ed g ai t t as k, bu t si gn ifi ca nt di ffer en ce s d ur in g am bu la to ry ass ess -m en t. Tu rnin g ch ar ac -te ris tic s i n P D pat ie nt s a re m or e no rmal d ur in g ob se rv at io n t ha n du rin g d ai ly l ife . M ito m a (2 01 0) [5 0] Ac ce le ro m et er (P or ta ble G ai t Rh yt hm og ra m) G ai t 22 P D p at ie nt s 11 h ea lth y co nt ro ls Con tin uou sly -24 hou rs Wa ist Am pl itu de o f t he ga it a cc el er at io n an d t he g ai t c yc le . - -Ra msp er ge r (2 016 ) [ 49 ] Th re e-ax ia l gy ro sc op es a nd ac ce ler om et er s (Re hac om ®) D ys ki ne sia 3 P D w ith p at ie nt s w ith d ys kin es ias 7 P D p at ie nt s wi thout dy sk in es ias -12 w ee ks Lat er al si de of t he m os t aff ec ted an kl e Lab or at or y-dev el -op ed a lgor ith m to de te ct d ys ki ne sia s La b-ba se d s tu dy : 98 % s pe ci fic ity , 8 5% se nsi tiv ity , a nd 9 6% ac cu ra cy i n d et ec -tio n o f d ys ki ne sia s. Co rre lat io n o f 0 .61 w ith t he c lin ic al se ve rit y s co re . Algor ith m de te ct s dy sk in esi as a lso for non dys ki ne tic le gs .

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56 Ro ch es te r (2 012 ) [ 48 ] St ep m on ito r (Ac tiv PA L TM) PD : a m bu lat or y ac tiv ity a fte r D BS 17 P D p at ie nt s N one W or n c on tin -uo us ly e xc ep t du rin g b at hin g. H om e v isi t at t he s tu dy st ar t a nd en d 2x 7 d ay s ( 6 w ee ks b ef or e an d 6 w ee ks af te r) In f ro nt o f t he thi gh Vo lu m e a nd p at -te rn o f a m bu lat or y ac tiv ity ( nu m be r o f st ep s p er d ay , a cc u-m ul at io n, d iv er sit y an d v ar ia bi lit y o f w al ki ng t im e) , FO G , g ai t s pe ed , ex te nd ed a ct iv iti es of d ai ly liv ing . UP D RS w as si gni f-ic an tly c or re lat ed wi th w al ki ng b out va ria bi lit y but no t w ith v ol um e o f w alk in g. N um be r o f w al ki ng b out s de crea se d a fte r D BS , p os sib ly d ue to a d ec re as e i n re st in g m om en ts du rin g a w al ki ng bout Te ra sh i ( 20 15 ) [43 ] Ac ce le ro m et er (p or ta ble g ai t rh yt hmo gr am ) W al ki ng p at te rn pat ie nt s w ith v as -cu la r p ar kin so ni sm (9 ) o r P D ( 39 ) 15 h ea lth y co nt ro ls Re mo ve d wh en c ha ng ing cl ot he s o r bat hi ng -24 -h c on tinu -ou s r ec or di ng Wa ist Th e “ am ou nt o f ov er al l m ov em en ts pe r 2 4 h , g ai t ac ce le rat io n, g ai t cy cl e. -Sim ila r d ist ur -ba nc es i n P D pat ie nt s a s i n vas cu la r p ar kin -so nis m . W ei ss ( 20 14 ) [51 ] Tr ia xa l ac ce ler om et er (D yn aPo rt ) PD : f re ez in g o f gai t 72 P D p at ie nt s N one -3 d ay s Be lt Ac ce le ra tion -de -riv ed g ai t f eat ur es in cl ud in g q ua nt ity (to ta l n um be r o f w al ki ng b out s, bout du rat io n, n um be r of s te ps , m ed ia n ca de nc e p er b out ) an d q ua lit y ( w id th of t he d om in an t pe ak i n t he p ow er sp ec tru m , s trid e re gu la rit y a nd t he ha rm on ic r at io ) N o si gn ifi ca nt ass oci at io n w as fo un d b et w ee n t he N ew F re ez in g O f G ai t Q ue st io nnair e sc or es a nd t he g ai t quan tit y m ea su re s (r= 0.1 65 , p >0 .16 7) -W ei ss ( 20 15 ) [47 ] Tr ia xa l ac ce ler om et er (D yn aPo rt ) G ai t ( re lat io n w ith c og ni tiv e fu nc tion ) 10 7 P D p at ie nt s N one -3 d ay s Lo w er b ac k Ca de nc e, va ria bi lit y, b ilat er al co or di nat io n, a nd dy nami c p os tu ra l co nt ro l. -Yo ne ya m a (2 013 ) [ 41 ] Ac ce le ro m et er (P or ta bl e g ai t rh yt hmo gr am ) G ai t 10 P D p at ie nt s 17 a ge -m at ch ed he al th y su bj ec ts -24 hou rs Wa ist G ai t p ea ks , r el at io n-sh ip b et we en gai t cy cl e a nd v er tic al ga it a cc el er at io n N o c or re lat io n be twe en gai t pa ra m et er s a nd U PD RS sco re . -Yo ne ya m a (2 016 ) [ 39 ] Por ta ble rh yt hmo gr am (M im am or i-gai t sy st em) Am bu lat or y G ai t Be ha vio r 26 P D p at ie nt s, 2 6 pat ie nt s w ith M CI or d em en tia 13 H ea lth y co nt ro ls Ex ce pt w he n ch an gin g cl ot he s o r ta ki ng a b at h. -24 h Wa ist G ai t p ea ks a nd re lat io ns hi p be tw ee n g ai t c yc le an d v er tic al g ai t ac cel er ati on

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57 Tr em or Bra yb ro ok (2 016 ) Ac ce ler om et er (P ar kin so n Ki ne tigr ap h) Tr em or 85 P D p at ie nt s N one Con tin uou sly , ho w ev er o nl y 9: 00 -1 8: 00 w as us ed i n t he ana ly sis -6 d ay s W ris t ( m os t aff ec ted si de ) Pr op or tion of Tr em or Ti m e. La bo rat or y-ba se d vi de o o bs er vat io n: se ns iti vi ty 8 8. 7% , sel ec tiv ity 8 9. 5% .. A fi ne a m pl itu de pos tur al o r ki ne tic t re m or or a t re m or t hat di d n ot a ffe ct t he up pe r a rm c ou ld no t b e d et ec te d. Ph ysi ca l a ct iv ity ab ov e 3 H z i s an i m po rt an t ar te fa ct . Va n S om er en (19 92 ) Ac ce le ro m et er (EN D EVC O P ic o-ch ip m od el 1 2) Tr em or re cor di ng be fo re a nd a fte r tha lam ot om y 6 t re m or p at ie nt s 10 y ou ng an d 1 0 a ge d co nt ro ls Sp or ts a nd sho w er ing w er e e xc ep te d. -24 h Wr ist Am ou nt (pr op or -tio n o f t re m or o r m ov em en ts p er tim e u ni t) a nd in te ns ity (av er ag e ac ce le rat io n a m pl i-tu de ) o f t re m or . G oo d c or re lat io n w ith U PD RS . Re peti tiv e m ov em en ts l ike ‘kn itt in g’ m ig ht re semb le tr em or . O n a ve ra ge a fa lse p osi tiv e r at e of 4% . Com bi ne d M ac tie r e t a l (2 01 5) [5 4] Ac ce ler om et er (Ac tiv PA L) & F al l di ar y ( pap er ) Fa lls & g ai t 11 1 P D p at ie nt s N one -12 m on th s 7 d ay s Up pe r t hi gh Ac ce le rom et ry : pos tur es , w al ki ng , nu mb er o f s tep s Fa ll d ia ry : n um be r of fa lls Ac ce le ro m et ry a nd U PD RS c ou ld n ot id en tif y r ecur ren t fal ler s. Se lf-re po rt m ay be s us ce pt ib le to b ia s d ue t o co gni tiv e d ecl in e or l ay d efi ni tio ns of fa lli ng W ei ss ( 20 14 ) [2 014 ] Ac ce ler om et er (D yn aP or t) & fal l d iar y ( pap er ) PD : f al le rs o r non -fa lle rs 10 7 P D p at ie nt s N one Ac ce le ro m et er no t d ur in g ac tiv iti es l ike sho w er ing Ye s 3 d ay s 1 y ea r Lo w er b ac k Ac ce le rom et ry : W al ki ng quan tit y an d q ua lit y ( to ta l nu m be r o f a ct iv ity bo ut s, t ot al n um be r of s te ps , m ed ia n ac tiv ity b out du rat io n) . Fa ll d ia ry : n um be r of fa lls Tr ad iti on al m ea su re s c ou ld no t p re di ct t im e til l fi rs t f al l, w hi le a c-ce le rom et er y c ou ld. N o si gn ifi ca nt c or -re lat io ns b et w ee n th e U PD RS m ot or sc or e a nd t he a cc el -er at io n d er iv ed g ai t m ea su re s ( R= 0.1 38 ) -Ce re da (20 10 ) [57 ] Ac ce le ro m et er (S en seWe ar Ar m ba nd ) & O N /O FF d iar y En er gy e xp en di -tu re a nd p hy sic al ac tiv ity d ur in g O N /O FF p er io ds in PD 6 P D p at ie nt s N one -7 d ay s Tr ic ep s r eg io n Ac cel er om et er : to ta l d ai ly e ne rg y ex pen di tur e, sl eep du rat io n a nd ph ysi ca l a ct iv ity . D ia ry : m ed ic at io n st at us ( O N /O FF / dy sk in es ia) O N /O FF d ia ry c ou ld de te ct re duc tion in O FF t im e w hi le SW A c ou ld n ot .