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Shaky and unsteady: Dynamic posturography in essential tremor
Journal of the Neurological Sciences 385 (2018) 12–16
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Shaky and unsteady: Dynamic posturography in essential tremor a,b
c
b
Shweta Prasad , Selva Ganapathy Velayutham , Venkateswara Reddy Reddam , Albert Stezin ⁎ Ketan Jhunjhunwalaa,b, Pramod Kumar Palb, a b c
T a,b
,
Department of Clinical Neurosciences, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India Department of Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India Department of Neurological Rehabilitation, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India
A R T I C L E I N F O
A B S T R A C T
Keywords: Essential tremor Dynamic posturography Balance control Cerebellar dysfunction
Background: The spectrum of symptoms exhibited by patients with essential tremor (ET) extends far beyond the classical tremor. This study aims to explore and establish the presence of subtle balance abnormalities in ET using dynamic posturography (DP). Methods: DP was performed on 18 patients with ET and 26 controls. Diagnosis of ET was based on the Consensus Statement of the Movement Disorder Society on Tremor. Dynamic stability which included the overall balance index, anterior-posterior index and mediolateral index, and limits of stability were measured. Results: Patients with ET had significantly impaired balance indices. Impairment of dynamic stability revealed poor static balance control in all directions. Lower limits of stability scores indicated a smaller range of motion prior to which patients have to shift foot balance. No correlations were observed between age at evaluation, age at onset, duration of illness and the balance indices. Conclusions: Dynamic posturography reveals significant balance impairment in patients with ET which is unrelated to the age at onset, age at evaluation or duration of illness. This finding concurs with pre-existing reports and adds to the growing body evidence of cerebellar involvement in ET.
1. Introduction Essential tremor (ET) is a highly prevalent movement disorder [1], classically associated with an action tremor of the upper limbs, occasionally involving the head, legs and trunk. ET was always considered to be a monosymptomatic disorder with a relatively benign course. In fact, according to the diagnostic criteria for ET, the presence of other abnormal findings on a neurological examination is indicative of a disorder other than ET [2]. However, this view has been under scrutiny due to several reports suggesting a symptom complex extending beyond the tremor. Patients with ET have been reported to suffer from a variety of symptoms ranging from gait and balance impairments to alterations in cognition [3–5]. Although gait and balance impairment has been known for several decades, the reports were usually anecdotal, with the impairment attributed to old age rather than the disease [6]. Singer et al. [7], provided the first proof of balance and gait impairment in ET. Post this, several studies have concurred with this finding either through the utilization of clinical examinations and scores or complex laboratory
analysis [8–16]. An increase in the number of missteps during tandem gait has been consistently reported in studies which have focused on abnormalities in neurological examination in patients with ET [7–9,11,14,15]. Gait analysis has shown a reduction in the velocity of normal and tandem gait, increased step variability and step width, and a reduction in stride length [8,9,11,12,15]. Posturographic assessment has revealed significant impairments of both static and dynamic balance control in patients with ET [8,10,12,13,16]. However, the actual implication of this impairment is still unclear and the need for therapeutic intervention is doubtful [17]. The presence of subtle cerebellar dysfunction in ET has been previously reported [18,19]. In view of this, gait and balance abnormalities should be expected in this disorder. There are limited studies which have utilized dynamic posturography (DP) to assess the balance impairment in ET [8]. This study aims to explore and establish the presence of subtle balance abnormalities in ET by DP.
Abbreviations: AAO, age at onset; API, anterior-posterior index; BMI, body mass index; DP, dynamic posturography; ET, essential tremor; HT, head tremor; LOS, limits of stability; MLI, mediolateral index; OBI, overall balance index; SP, static posturography ⁎ Corresponding author. E-mail address: pal.pramod@rediffmail.com (P.K. Pal). https://doi.org/10.1016/j.jns.2017.12.003 Received 2 August 2017; Received in revised form 24 October 2017; Accepted 1 December 2017 Available online 05 December 2017 0022-510X/ © 2017 Elsevier B.V. All rights reserved.
Journal of the Neurological Sciences 385 (2018) 12–16
S. Prasad et al.
2. Material and methods
Table 1 Demographic details of patients with essential tremor and controls.
2.1. Subject recruitment and clinical evaluation This study was conducted at the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. A total of 18 patients with “classic” ET (according to the Consensus Statement of the Movement Disorder Society on Tremor) [20] were included in this study. Tremor of the upper limbs was assessed while (1) both hands were kept on the lap, (2) upper limbs were extended at the elbows and held in front of the chest, (3) upper limbs were flexed at the elbow and held in front of the chest, (4) performing the finger-to-nose test and (5) writing a sentence and drawing Archimedes spirals. Tremor of the lower limbs was assessed while (1) the patient was seated in a chair with feet resting on the floor, (2) the patient was lying on the bed with lower limb lifted off the bed with flexion at the hip and knee, and (3) performing the knee-heel test. A diagnosis of ET was confirmed by a trained movement disorder specialist (author-PKP). Basic demographic data and parameters to calculate body mass index (BMI) – height and weight, was collected. BMI had to be calculated as it plays a crucial role during estimation of DP results. The controls were age and gender matched healthy subjects who gave consent to participate in the study. Patients with ET and healthy controls underwent a neurological examination with emphasis on detection of abnormalities of eye movements, impaired balance and gait, and extrapyramidal signs. None of the subjects included in this study had musculoskeletal problems, joint problems, peripheral neuropathy or other neurological conditions which could have affected gait and balance. Neither the patients with ET nor the controls were on medications which could have caused impairment of balance.
Gender (M: F) Age at presentation (years) Age at onset (years) Duration of illness (years) Body mass index (kg/ m2)
Essential tremor (n = 18)
Controls (n = 26)
p-Value
14:04 44.22 ± 20.89
21:05 46.38 ± 16.53
NS NS
34.83 ± 20.35 9.5 ± 4.57
– –
– –
22.79 ± 3.14
24.15 ± 3.15
NS
analyzed using the t-test and the chi-square test was used for categorical variables. Correlations between parameters of ET and results of posturography were evaluated by performing Pearson's correlation. Statistical significance was set at p < 0.05. 3. Results 3.1. Demographic data A total of 44 subjects were studied, which included 18 patients with ET and 26 healthy controls. Men outnumbered women in both groups and there was no significant difference in the age at evaluation. The mean age at onset (AAO) of ET was 34.83 ± 20.35 years and the mean duration of illness was 9.5 ± 4.57 years. Both groups had similar BMI's at 22.79 ± 3.14 kg/m2 and 24.15 ± 3.15 kg/m2. Details are provided in Table 1. The treatment profile of patients with ET was as follows: 64.70% were on propranolol (33.33 ± 9.42 mg/day), 35.29% were on primidone (375 ± 0 mg/day) and 23.5% were on clonazepam (0.62 ± 0.37 mg/day). One patient was drug naïve at the time of DP.
2.2. Dynamic posturography Balance was tested using the Biodex Balance System. This system consists of a suspended computerized circular platform that can tilt 20° in all directions from the horizontal. The system's microprocessor-based actuator controls the extent of the surface instability of the platform. The surface instability can be adjusted from Level 8 (most stable) to Level 1 (least stable). Level 8 was used for the examination of balance in all the subjects. Prior to the actual test all subjects were explained and oriented to the test in training mode. The subjects were tested for dynamic stability and limits of stability (LOS). Dynamic stability, included (a) Overall balance index (OBI) which is the ability to control balance in all directions, (b) Anteriorposterior index (API) – front to back balance, and (c) Mediolateral index (MLI) – side-to-side balance. The degree of impairment of balance indices was obtained from the difference between the actual and predictive values. LOS is defined as the area over which a subject can safely move without changing the base of support towards the target, which appears randomly in eight directions. Each target appears only once during the test. The DP instrument tests the LOS by displaying the blinking target on a screen placed in front of the subject. Subjects are instructed to move their centres of mass toward the target, without changing the foot position. In the present study, LOS was assessed in eight directions – forward (F), backward (B), right (R), left (L), forward-right (FR), forward-left (FL), backward-right (BR) and backward-left (BL). Time taken for completion of the LOS test was also recorded. Higher scores in the balance indices and time taken for completion of the LOS test are indicative of a poor balance whereas higher scores in the LOS test are representative of better stability.
3.2. Dynamic posturography DP revealed impaired balance indices in patients with ET in comparison to controls (Table 2, Fig. 1). The OBI was significantly higher indicating poor balance in all directions. Similarly, the API and MPI were also higher implying poor balance control in the forward-backward and middle-lateral directions. The LOS test revealed significantly lower scores in patients with ET. Although stability was found to be impaired in all directions in ET, significantly poor scores were observed only in the forward-right and forward-left directions, and the impairment in the backward-left direction was found to near significance (Table 3, Fig. 2). Patients with ET took significantly longer to complete the LOS test in comparison to healthy controls. 3.3. Correlations Pearson's correlation was performed between the age at evaluation, AAO of illness and duration of illness with all the balance indices. No significant correlations were observed between any of the parameters. Table 2 Results of dynamic posturography in patients with essential tremor and controls.
2.3. Statistical analysis Descriptive statistical analysis was performed for the demographic features of patients with ET and controls. Continuous variables were
Dynamic posturography
Essential tremor (n = 18)
Controls (n = 26)
p-Value
Overall balance index Anterior posterior index Mediolateral index Limits of stability Time taken to complete
2.59 ± 1.03 2.13 ± 0.95
1.95 ± 0.54 1.58 ± 0.51
< 0.01 < 0.05
1.85 ± 0.71 16.36 ± 11.72 205.33 ± 65.05
1.22 ± 0.40 27.38 ± 10.32 154.61 ± 60.31
< 0.01 < 0.01 < 0.05
Limits of stability test (s).
13
Journal of the Neurological Sciences 385 (2018) 12–16
S. Prasad et al.
Fig. 1. Comparisons of balance indices in patients with essential tremor and controls, (A) Dynamic stability (B) Limits of stability. OBI: overall balance index; API: anterior posterior index; MLI: mediolateral index; LOS: limits of stability.
impairment of balance in patients with ET by using DP. All the indices of balance – dynamic stability and LOS were found to be abnormal in ET. The impairment of dynamic stability measured by OBI, API and MLI implies that these patients have difficulties with stability while standing still and this unsteadiness is present in all directions. A poor LOS score indicates that patients with ET have a smaller range of motion in a direction prior to which they are required to change foot position. Additionally, patients with ET also took significantly longer to complete the LOS task which implies poor balance control. The spectrum of reported balance impairment in ET ranges from normal [13] to severely impaired [8]. These contradictory findings may be attributable to several factors: (a) differences in severity of symptoms of patients assessed–mild vs severe, (b) diagnostic criteria–inclusion vs exclusion of patients with mild cerebellar symptoms, (c) methods of evaluation- bedside tests and scales vs dynamic or static posturography [17]. In our study, quantitative assessment of balance impairment in ET was assessed through the use of DP which measures body sway under different conditions. DP is a highly sensitive method of balance assessment in which the recording platform moves in accordance with body sway. Owing to this DP has the ability to accurately measure minute alterations in balance when compared to static posturography (SP). The superiority of DP over SP has been established based on reports of patients with degenerative [21] or focal cerebellar lesions [22] wherein SP reported minimal to normal balance whereas DP exhibited significant impairments in balance. Similarly, abnormalities in ET have also been found to be more prominent in DP [8]. This method has also used to measure the severity of balance impairments in progressive supranuclear palsy and its subtypes [23]. The effect of duration of illness on the severity of balance impairment is debatable. Rao et al. [15], had reported progressive worsening of balance indices with the disease duration or severity. Whereas, Hoskovcova et al. [12] reported no significant associations between disease duration and balance indices. The latter result implies the presence of clinical or subclinical balance impairments in all ET patients irrespective of duration of disease. Perhaps patients with shorter duration of illness possess better compensatory mechanisms owing to which the balance deficits remain subclinical. The effect of a head tremor (HT) on balance impairment has been explored by Bove et al. [13], who reported balance impairments in a subgroup of ET patients with HT in comparison to those without head tremor, they failed to report any impairment when patients with ET were compared with controls. The hypothesis suggested for this finding was that HT alters the flow of visual information and perhaps the changes observed may be a mechanical reflection of the head tremor.
Table 3 Limits of stability in patients with essential tremor and controls. Directions
Essential tremor (n = 18)
Controls (n = 26)
p-Value
Forward Backward Right Left Forward-right Forward-left Backward-right Backward-left
22.27 16.61 14.83 18.11 21.33 19.88 18.11 17 ±
32.5 ± 18.82 26.15 ± 19.11 23.30 ± 18.08 24.69 ± 11.70 33.03 ± 18.65 30.26 ± 13.38 27.26 ± 17.91 25.38 ± 16.13
NS NS NS NS < 0.05 < 0.05 NS =0.06
± 17.71 ± 15.33 ± 11.46 ± 18.14 ± 16.91 ± 13.84 ± 14.69 11.84
NS: not significant.
Fig. 2. Limits of stability in patients with essential tremor and controls.
4. Discussion Balance impairment in ET, although widely discussed has seldom been objectively measured. Our study demonstrates significant 14
Journal of the Neurological Sciences 385 (2018) 12–16
S. Prasad et al.
worsening [30] to no effect [8,9]. Further studies are required to study the clinical significance of these impairments and assess if these impairments are more prevalent in specific subgroups of patients with ET.
Other studies must repeat this result to prove its validity and importance. Several studies have reported a correlation between the presence of a midline tremor and gait and balance alterations in patients with ET [10,12]. The midline tremor being indicative of a higher extent of cerebellar involvement hence producing gait and balance abnormalities. We did not observe any correlations between the balance indices and parameters such as age at evaluation, AAO and duration of illness. The lack of a relationship between AAO, duration of illness and parameters of balance may be attributable to an imprecise AAO reported by patients. As they tend to indicate the moment the tremor started to interfere with activities of daily living rather than the precise onset of tremor. Impaired balance and gait disturbances are symptoms which complement each other and frequently occur together. Tandem walking impairment in ET has been frequently reported. Patients with ET have been found to exhibit an increased number of missteps and shortened stride length with tandem gait [7,11]. Rao et al. [15], demonstrated decrements in gait speed, dynamic balance and gait symmetry during a standard walk and definite balance impairment during tandem walking. Cinar et al. [24], have reported the probable utility of the first misstep in tandem gait as a sign of impending or ongoing balance impairment in ET. Patients with ET have also been shown to receive lower scores on scales such as the Berg Balance Scale [9,10,14] and Dynamic Gait Index [10]. Balance impairments in ET may be attributable to cerebellar dysfunction. Patterns of DP results are similar to those observed in cerebellar lesions [11] and support the theories of the association of ET with cerebellar dysfunction. Several clinical, neuropathological and neuroimaging studies have supported the possible role of the cerebellum in the pathogenesis of ET. The wide range of clinical features which suggest a cerebellar or cerebellar outflow origin in ET include but are not limited to intention tremor, gait and balance abnormalities, oculomotor abnormalities and subtle dysarthria [25]. Neuropathological studies have identified numerous degenerative and structural changes in the ET cerebellum. These primarily include the Purkinje cell and changes have been observed in the dendritic compartment, cell body and axonal compartment. Additionally, hypertrophy of basket cell axonal processes and altered distribution of climbing fiber-Purkinje cell synapses [26]. Finally, a large number of neuroimaging studies have demonstrated structural and functional abnormalities in several parts of the anterior and posterior cerebellar lobules [27]. Although a valid pathophysiological explanation exists for the presence of impaired balance in ET, it is crucial to consider other causes for the findings. However, in our study, none of the patients were on medications such as phenytoin which often produces cerebellar dysfunction nor had any medical co-morbidities such as vestibular dysfunction which can impair balance. This study has several limitations owing to the small sample size of patients evaluated. Although the results are clearly indicative of impairment of balance in ET, we were unable to report correlations of disease severity and balance impairment as formal scoring scales were not utilized to assess disease severity. Not all patients with ET were off medications during the DP; this may have produced variations in the results. However, based on the treatment profile, the medications are unlikely to have contributed to the observed abnormality in balance. The implications of balance and gait impairment in ET are multifold. The presence of this impairment questions the current diagnostic criteria for ET and implores for the possible inclusion of mild gait and balance deficits into future diagnostic criteria. The actual impact of the problem on patient care and the need for therapeutic intervention remains uncertain. Few studies have explored the effect of medication on gait and balance in ET. Ethanol was reported to produce a transient 30% reduction in missteps and improve the step width and step variability [28]. The reports of the effects of thalamic DBS on balance and gait are variable, and range from improvement [16,29] to
5. Conclusions Dynamic posturography reveals significant balance impairment in patients with ET which is unrelated to the age at onset, age at evaluation or duration of illness. This finding concurs with pre-existing reports and adds to the growing body evidence of cerebellar involvement in ET. Further studies are mandatory to establish the clinical implications of these impairments. Financial disclosure/conflict of interest None of the authors have any financial disclosure to make or have any conflict of interest. Source of funding Nil. References [1] E.D. Louis, J.J. Ferreira, How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor, Mov. Disord. 25 (5) (2010) 534–541. [2] F.B. Nahab, E. Peckham, M. Hallett, Essential tremor, deceptively simple, Pract. Neurol. 7 (4) (2007) 222–233. [3] V. Chandran, P.K. Pal, Essential tremor: beyond the motor features, Parkinsonism Relat. Disord. 18 (5) (2012) 407–413. [4] E.D. Louis, M.S. Okun, It is time to remove the 'benign' from the essential tremor label, Parkinsonism Relat. Disord. 17 (7) (2011) 516–520. [5] F. Bermejo-Pareja, Essential tremor—a neurodegenerative disorder associated with cognitive defects? Nat. Rev. Neurol. 7 (5) (2011) 273–282. [6] E. Critchley, Clinical manifestations of essential tremor, J. Neurol. Neurosurg. Psychiatry 35 (3) (1972) 365–372. [7] C. Singer, J. Sanchez-Ramos, W.J. Weiner, Gait abnormality in essential tremor, Mov. Disord. 9 (2) (1994) 193–196. [8] M. Kronenbuerger, J. Konczak, W. Ziegler, P. Buderath, B. Frank, V.A. Coenen, et al., Balance and motor speech impairment in essential tremor, Cerebellum 8 (3) (2009) 389–398. [9] G.M. Earhart, B.R. Clark, S.D. Tabbal, J.S. Perlmutter, Gait and balance in essential tremor: variable effects of bilateral thalamic stimulation, Mov. Disord. 24 (3) (2009) 386–391. [10] S.L. Parisi, M.E. Héroux, E.G. Culham, K.E. Norman, Functional mobility and postural control in essential tremor, Arch. Phys. Med. Rehabil. 87 (10) (2006) 1357–1364. [11] H. Stolze, G. Petersen, J. Raethjen, R. Wenzelburger, G. Deuschl, The gait disorder of advanced essential tremor, Brain 124 (Pt 11) (2001) 2278–2286. [12] M. Hoskovcova, O. Ulmanova, O. Sprdlik, T. Sieger, J. Novakova, R. Jech, et al., Disorders of balance and gait in essential tremor are associated with midline tremor and age, Cerebellum 12 (1) (2013) 27–34. [13] M. Bove, L. Marinelli, L. Avanzino, R. Marchese, G. Abbruzzese, Posturographic analysis of balance control in patients with essential tremor, Mov. Disord. 21 (2) (2006) 192–198. [14] E.D. Louis, A.K. Rao, M. Gerbin, Functional correlates of gait and balance difficulty in essential tremor: balance confidence, near misses and falls, Gait Posture 35 (1) (2012) 43–47. [15] A.K. Rao, A. Gillman, E.D. Louis, Quantitative gait analysis in essential tremor reveals impairments that are maintained into advanced age, Gait Posture 34 (1) (2011) 65–70. [16] W.G. Ondo, M. Almaguer, H. Cohen, Computerized posturography balance assessment of patients with bilateral ventralis intermedius nuclei deep brain stimulation, Mov. Disord. 21 (12) (2006) 2243–2247. [17] D. Arkadir, E.D. Louis, The balance and gait disorder of essential tremor: what does this mean for patients? Ther. Adv. Neurol. Disord. 6 (4) (2013) 229–236. [18] R. Hanajima, R. Tsutsumi, Y. Shirota, T. Shimizu, N. Tanaka, Y. Ugawa, Cerebellar dysfunction in essential tremor, Mov. Disord. 31 (8) (2016) 1230–1234. [19] A. Buijink, M. Broersma, A. van der Stouwe, G. van Wingen, P. Groot, J. Speelman, et al., Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor, Parkinsonism Relat. Disord. 21 (4) (2015) 383–388. [20] G. Deuschl, P. Bain, M. Brin, Consensus statement of the Movement Disorder Society on tremor. Ad Hoc Scientific Committee, Mov. Disord. 13 (Suppl. 3) (1998) 2–23. [21] R.W. Baloh, K.M. Jacobson, K. Beykirch, V. Honrubia, Static and dynamic posturography in patients with vestibular and cerebellar lesions, Arch. Neurol. 55 (5)
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[26] E.D. Louis, Linking essential tremor to the cerebellum: neuropathological evidence, Cerebellum 15 (3) (2016) 235–242. [27] A. Cerasa, A. Quattrone, Linking essential tremor to the cerebellum-neuroimaging evidence, Cerebellum 15 (3) (2016) 263–275. [28] S. Klebe, H. Stolze, K. Grensing, J. Volkmann, R. Wenzelburger, G. Deuschl, Influence of alcohol on gait in patients with essential tremor, Neurology 65 (1) (2005) 96–101. [29] A. Fasano, J. Herzog, J. Raethjen, F.E. Rose, M. Muthuraman, J. Volkmann, et al., Gait ataxia in essential tremor is differentially modulated by thalamic stimulation, Brain 133 (Pt 12) (2010) 3635–3648. [30] R. Pahwa, K.E. Lyons, S.B. Wilkinson, R.K. Simpson Jr., W.G. Ondo, D. Tarsy, et al., Long-term evaluation of deep brain stimulation of the thalamus, J. Neurosurg. 104 (4) (2006) 506–512.
(1998) 649–654. [22] J. Konczak, B. Schoch, A. Dimitrova, E. Gizewski, D. Timmann, Functional recovery of children and adolescents after cerebellar tumour resection, Brain 128 (Pt 6) (2005) 1428–1441. [23] S.A. Pasha, R. Yadav, M. Ganeshan, J. Saini, A. Gupta, M. Sandhya, et al., Correlation between qualitative balance indices, dynamic posturography and structural brain imaging in patients with progressive supranuclear palsy and its subtypes, Neurol. India 64 (4) (2016) 633–639. [24] N. Cinar, S. Sahin, T. Okluoglu Onay, S. Karsidag, Balance in essential tremor during tandem gait: is the first mis-step an important finding? J. Clin. Neurosci. 20 (10) (2013) 1433–1437. [25] J. Benito-Leon, A. Labiano-Fontcuberta, Linking essential tremor to the cerebellum: clinical evidence, Cerebellum 15 (3) (2016) 253–262.
16
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Shaky and unsteady: Dynamic posturography in essential tremor a,b
c
b
Shweta Prasad , Selva Ganapathy Velayutham , Venkateswara Reddy Reddam , Albert Stezin ⁎ Ketan Jhunjhunwalaa,b, Pramod Kumar Palb, a b c
T a,b
,
Department of Clinical Neurosciences, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India Department of Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India Department of Neurological Rehabilitation, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India
A R T I C L E I N F O
A B S T R A C T
Keywords: Essential tremor Dynamic posturography Balance control Cerebellar dysfunction
Background: The spectrum of symptoms exhibited by patients with essential tremor (ET) extends far beyond the classical tremor. This study aims to explore and establish the presence of subtle balance abnormalities in ET using dynamic posturography (DP). Methods: DP was performed on 18 patients with ET and 26 controls. Diagnosis of ET was based on the Consensus Statement of the Movement Disorder Society on Tremor. Dynamic stability which included the overall balance index, anterior-posterior index and mediolateral index, and limits of stability were measured. Results: Patients with ET had significantly impaired balance indices. Impairment of dynamic stability revealed poor static balance control in all directions. Lower limits of stability scores indicated a smaller range of motion prior to which patients have to shift foot balance. No correlations were observed between age at evaluation, age at onset, duration of illness and the balance indices. Conclusions: Dynamic posturography reveals significant balance impairment in patients with ET which is unrelated to the age at onset, age at evaluation or duration of illness. This finding concurs with pre-existing reports and adds to the growing body evidence of cerebellar involvement in ET.
1. Introduction Essential tremor (ET) is a highly prevalent movement disorder [1], classically associated with an action tremor of the upper limbs, occasionally involving the head, legs and trunk. ET was always considered to be a monosymptomatic disorder with a relatively benign course. In fact, according to the diagnostic criteria for ET, the presence of other abnormal findings on a neurological examination is indicative of a disorder other than ET [2]. However, this view has been under scrutiny due to several reports suggesting a symptom complex extending beyond the tremor. Patients with ET have been reported to suffer from a variety of symptoms ranging from gait and balance impairments to alterations in cognition [3–5]. Although gait and balance impairment has been known for several decades, the reports were usually anecdotal, with the impairment attributed to old age rather than the disease [6]. Singer et al. [7], provided the first proof of balance and gait impairment in ET. Post this, several studies have concurred with this finding either through the utilization of clinical examinations and scores or complex laboratory
analysis [8–16]. An increase in the number of missteps during tandem gait has been consistently reported in studies which have focused on abnormalities in neurological examination in patients with ET [7–9,11,14,15]. Gait analysis has shown a reduction in the velocity of normal and tandem gait, increased step variability and step width, and a reduction in stride length [8,9,11,12,15]. Posturographic assessment has revealed significant impairments of both static and dynamic balance control in patients with ET [8,10,12,13,16]. However, the actual implication of this impairment is still unclear and the need for therapeutic intervention is doubtful [17]. The presence of subtle cerebellar dysfunction in ET has been previously reported [18,19]. In view of this, gait and balance abnormalities should be expected in this disorder. There are limited studies which have utilized dynamic posturography (DP) to assess the balance impairment in ET [8]. This study aims to explore and establish the presence of subtle balance abnormalities in ET by DP.
Abbreviations: AAO, age at onset; API, anterior-posterior index; BMI, body mass index; DP, dynamic posturography; ET, essential tremor; HT, head tremor; LOS, limits of stability; MLI, mediolateral index; OBI, overall balance index; SP, static posturography ⁎ Corresponding author. E-mail address: pal.pramod@rediffmail.com (P.K. Pal). https://doi.org/10.1016/j.jns.2017.12.003 Received 2 August 2017; Received in revised form 24 October 2017; Accepted 1 December 2017 Available online 05 December 2017 0022-510X/ © 2017 Elsevier B.V. All rights reserved.
Journal of the Neurological Sciences 385 (2018) 12–16
S. Prasad et al.
2. Material and methods
Table 1 Demographic details of patients with essential tremor and controls.
2.1. Subject recruitment and clinical evaluation This study was conducted at the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. A total of 18 patients with “classic” ET (according to the Consensus Statement of the Movement Disorder Society on Tremor) [20] were included in this study. Tremor of the upper limbs was assessed while (1) both hands were kept on the lap, (2) upper limbs were extended at the elbows and held in front of the chest, (3) upper limbs were flexed at the elbow and held in front of the chest, (4) performing the finger-to-nose test and (5) writing a sentence and drawing Archimedes spirals. Tremor of the lower limbs was assessed while (1) the patient was seated in a chair with feet resting on the floor, (2) the patient was lying on the bed with lower limb lifted off the bed with flexion at the hip and knee, and (3) performing the knee-heel test. A diagnosis of ET was confirmed by a trained movement disorder specialist (author-PKP). Basic demographic data and parameters to calculate body mass index (BMI) – height and weight, was collected. BMI had to be calculated as it plays a crucial role during estimation of DP results. The controls were age and gender matched healthy subjects who gave consent to participate in the study. Patients with ET and healthy controls underwent a neurological examination with emphasis on detection of abnormalities of eye movements, impaired balance and gait, and extrapyramidal signs. None of the subjects included in this study had musculoskeletal problems, joint problems, peripheral neuropathy or other neurological conditions which could have affected gait and balance. Neither the patients with ET nor the controls were on medications which could have caused impairment of balance.
Gender (M: F) Age at presentation (years) Age at onset (years) Duration of illness (years) Body mass index (kg/ m2)
Essential tremor (n = 18)
Controls (n = 26)
p-Value
14:04 44.22 ± 20.89
21:05 46.38 ± 16.53
NS NS
34.83 ± 20.35 9.5 ± 4.57
– –
– –
22.79 ± 3.14
24.15 ± 3.15
NS
analyzed using the t-test and the chi-square test was used for categorical variables. Correlations between parameters of ET and results of posturography were evaluated by performing Pearson's correlation. Statistical significance was set at p < 0.05. 3. Results 3.1. Demographic data A total of 44 subjects were studied, which included 18 patients with ET and 26 healthy controls. Men outnumbered women in both groups and there was no significant difference in the age at evaluation. The mean age at onset (AAO) of ET was 34.83 ± 20.35 years and the mean duration of illness was 9.5 ± 4.57 years. Both groups had similar BMI's at 22.79 ± 3.14 kg/m2 and 24.15 ± 3.15 kg/m2. Details are provided in Table 1. The treatment profile of patients with ET was as follows: 64.70% were on propranolol (33.33 ± 9.42 mg/day), 35.29% were on primidone (375 ± 0 mg/day) and 23.5% were on clonazepam (0.62 ± 0.37 mg/day). One patient was drug naïve at the time of DP.
2.2. Dynamic posturography Balance was tested using the Biodex Balance System. This system consists of a suspended computerized circular platform that can tilt 20° in all directions from the horizontal. The system's microprocessor-based actuator controls the extent of the surface instability of the platform. The surface instability can be adjusted from Level 8 (most stable) to Level 1 (least stable). Level 8 was used for the examination of balance in all the subjects. Prior to the actual test all subjects were explained and oriented to the test in training mode. The subjects were tested for dynamic stability and limits of stability (LOS). Dynamic stability, included (a) Overall balance index (OBI) which is the ability to control balance in all directions, (b) Anteriorposterior index (API) – front to back balance, and (c) Mediolateral index (MLI) – side-to-side balance. The degree of impairment of balance indices was obtained from the difference between the actual and predictive values. LOS is defined as the area over which a subject can safely move without changing the base of support towards the target, which appears randomly in eight directions. Each target appears only once during the test. The DP instrument tests the LOS by displaying the blinking target on a screen placed in front of the subject. Subjects are instructed to move their centres of mass toward the target, without changing the foot position. In the present study, LOS was assessed in eight directions – forward (F), backward (B), right (R), left (L), forward-right (FR), forward-left (FL), backward-right (BR) and backward-left (BL). Time taken for completion of the LOS test was also recorded. Higher scores in the balance indices and time taken for completion of the LOS test are indicative of a poor balance whereas higher scores in the LOS test are representative of better stability.
3.2. Dynamic posturography DP revealed impaired balance indices in patients with ET in comparison to controls (Table 2, Fig. 1). The OBI was significantly higher indicating poor balance in all directions. Similarly, the API and MPI were also higher implying poor balance control in the forward-backward and middle-lateral directions. The LOS test revealed significantly lower scores in patients with ET. Although stability was found to be impaired in all directions in ET, significantly poor scores were observed only in the forward-right and forward-left directions, and the impairment in the backward-left direction was found to near significance (Table 3, Fig. 2). Patients with ET took significantly longer to complete the LOS test in comparison to healthy controls. 3.3. Correlations Pearson's correlation was performed between the age at evaluation, AAO of illness and duration of illness with all the balance indices. No significant correlations were observed between any of the parameters. Table 2 Results of dynamic posturography in patients with essential tremor and controls.
2.3. Statistical analysis Descriptive statistical analysis was performed for the demographic features of patients with ET and controls. Continuous variables were
Dynamic posturography
Essential tremor (n = 18)
Controls (n = 26)
p-Value
Overall balance index Anterior posterior index Mediolateral index Limits of stability Time taken to complete
2.59 ± 1.03 2.13 ± 0.95
1.95 ± 0.54 1.58 ± 0.51
< 0.01 < 0.05
1.85 ± 0.71 16.36 ± 11.72 205.33 ± 65.05
1.22 ± 0.40 27.38 ± 10.32 154.61 ± 60.31
< 0.01 < 0.01 < 0.05
Limits of stability test (s).
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Fig. 1. Comparisons of balance indices in patients with essential tremor and controls, (A) Dynamic stability (B) Limits of stability. OBI: overall balance index; API: anterior posterior index; MLI: mediolateral index; LOS: limits of stability.
impairment of balance in patients with ET by using DP. All the indices of balance – dynamic stability and LOS were found to be abnormal in ET. The impairment of dynamic stability measured by OBI, API and MLI implies that these patients have difficulties with stability while standing still and this unsteadiness is present in all directions. A poor LOS score indicates that patients with ET have a smaller range of motion in a direction prior to which they are required to change foot position. Additionally, patients with ET also took significantly longer to complete the LOS task which implies poor balance control. The spectrum of reported balance impairment in ET ranges from normal [13] to severely impaired [8]. These contradictory findings may be attributable to several factors: (a) differences in severity of symptoms of patients assessed–mild vs severe, (b) diagnostic criteria–inclusion vs exclusion of patients with mild cerebellar symptoms, (c) methods of evaluation- bedside tests and scales vs dynamic or static posturography [17]. In our study, quantitative assessment of balance impairment in ET was assessed through the use of DP which measures body sway under different conditions. DP is a highly sensitive method of balance assessment in which the recording platform moves in accordance with body sway. Owing to this DP has the ability to accurately measure minute alterations in balance when compared to static posturography (SP). The superiority of DP over SP has been established based on reports of patients with degenerative [21] or focal cerebellar lesions [22] wherein SP reported minimal to normal balance whereas DP exhibited significant impairments in balance. Similarly, abnormalities in ET have also been found to be more prominent in DP [8]. This method has also used to measure the severity of balance impairments in progressive supranuclear palsy and its subtypes [23]. The effect of duration of illness on the severity of balance impairment is debatable. Rao et al. [15], had reported progressive worsening of balance indices with the disease duration or severity. Whereas, Hoskovcova et al. [12] reported no significant associations between disease duration and balance indices. The latter result implies the presence of clinical or subclinical balance impairments in all ET patients irrespective of duration of disease. Perhaps patients with shorter duration of illness possess better compensatory mechanisms owing to which the balance deficits remain subclinical. The effect of a head tremor (HT) on balance impairment has been explored by Bove et al. [13], who reported balance impairments in a subgroup of ET patients with HT in comparison to those without head tremor, they failed to report any impairment when patients with ET were compared with controls. The hypothesis suggested for this finding was that HT alters the flow of visual information and perhaps the changes observed may be a mechanical reflection of the head tremor.
Table 3 Limits of stability in patients with essential tremor and controls. Directions
Essential tremor (n = 18)
Controls (n = 26)
p-Value
Forward Backward Right Left Forward-right Forward-left Backward-right Backward-left
22.27 16.61 14.83 18.11 21.33 19.88 18.11 17 ±
32.5 ± 18.82 26.15 ± 19.11 23.30 ± 18.08 24.69 ± 11.70 33.03 ± 18.65 30.26 ± 13.38 27.26 ± 17.91 25.38 ± 16.13
NS NS NS NS < 0.05 < 0.05 NS =0.06
± 17.71 ± 15.33 ± 11.46 ± 18.14 ± 16.91 ± 13.84 ± 14.69 11.84
NS: not significant.
Fig. 2. Limits of stability in patients with essential tremor and controls.
4. Discussion Balance impairment in ET, although widely discussed has seldom been objectively measured. Our study demonstrates significant 14
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worsening [30] to no effect [8,9]. Further studies are required to study the clinical significance of these impairments and assess if these impairments are more prevalent in specific subgroups of patients with ET.
Other studies must repeat this result to prove its validity and importance. Several studies have reported a correlation between the presence of a midline tremor and gait and balance alterations in patients with ET [10,12]. The midline tremor being indicative of a higher extent of cerebellar involvement hence producing gait and balance abnormalities. We did not observe any correlations between the balance indices and parameters such as age at evaluation, AAO and duration of illness. The lack of a relationship between AAO, duration of illness and parameters of balance may be attributable to an imprecise AAO reported by patients. As they tend to indicate the moment the tremor started to interfere with activities of daily living rather than the precise onset of tremor. Impaired balance and gait disturbances are symptoms which complement each other and frequently occur together. Tandem walking impairment in ET has been frequently reported. Patients with ET have been found to exhibit an increased number of missteps and shortened stride length with tandem gait [7,11]. Rao et al. [15], demonstrated decrements in gait speed, dynamic balance and gait symmetry during a standard walk and definite balance impairment during tandem walking. Cinar et al. [24], have reported the probable utility of the first misstep in tandem gait as a sign of impending or ongoing balance impairment in ET. Patients with ET have also been shown to receive lower scores on scales such as the Berg Balance Scale [9,10,14] and Dynamic Gait Index [10]. Balance impairments in ET may be attributable to cerebellar dysfunction. Patterns of DP results are similar to those observed in cerebellar lesions [11] and support the theories of the association of ET with cerebellar dysfunction. Several clinical, neuropathological and neuroimaging studies have supported the possible role of the cerebellum in the pathogenesis of ET. The wide range of clinical features which suggest a cerebellar or cerebellar outflow origin in ET include but are not limited to intention tremor, gait and balance abnormalities, oculomotor abnormalities and subtle dysarthria [25]. Neuropathological studies have identified numerous degenerative and structural changes in the ET cerebellum. These primarily include the Purkinje cell and changes have been observed in the dendritic compartment, cell body and axonal compartment. Additionally, hypertrophy of basket cell axonal processes and altered distribution of climbing fiber-Purkinje cell synapses [26]. Finally, a large number of neuroimaging studies have demonstrated structural and functional abnormalities in several parts of the anterior and posterior cerebellar lobules [27]. Although a valid pathophysiological explanation exists for the presence of impaired balance in ET, it is crucial to consider other causes for the findings. However, in our study, none of the patients were on medications such as phenytoin which often produces cerebellar dysfunction nor had any medical co-morbidities such as vestibular dysfunction which can impair balance. This study has several limitations owing to the small sample size of patients evaluated. Although the results are clearly indicative of impairment of balance in ET, we were unable to report correlations of disease severity and balance impairment as formal scoring scales were not utilized to assess disease severity. Not all patients with ET were off medications during the DP; this may have produced variations in the results. However, based on the treatment profile, the medications are unlikely to have contributed to the observed abnormality in balance. The implications of balance and gait impairment in ET are multifold. The presence of this impairment questions the current diagnostic criteria for ET and implores for the possible inclusion of mild gait and balance deficits into future diagnostic criteria. The actual impact of the problem on patient care and the need for therapeutic intervention remains uncertain. Few studies have explored the effect of medication on gait and balance in ET. Ethanol was reported to produce a transient 30% reduction in missteps and improve the step width and step variability [28]. The reports of the effects of thalamic DBS on balance and gait are variable, and range from improvement [16,29] to
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