Gait freezing and speech disturbance in Parkinson s disease

Transcription

1 Neurol Sci (2014) 35: DOI /s ORIGINAL ARTICLE Gait freezing and speech disturbance in Parkinson s disease Hee Kyung Park Jong Yoon Yoo Miseon Kwon Jae-Hong Lee Sook Joung Lee Sung Reul Kim Mi Jung Kim Myoung C. Lee Sang Min Lee Sun Ju Chung Received: 12 April 2013 / Accepted: 7 August 2013 / Published online: 23 August 2013 Ó Springer-Verlag Italia 2013 Abstract Gait freezing and speech disturbance are disabling axial features of Parkinson s disease (PD). However, the pathogenesis of these features remains unclear. We investigated the relation between changes in gait freezing and speech disturbance using visual and auditory cues in PD. 18 PD patients, comprising of 9 patients with freezing (PDGF) and 9 without gait freezing were studied. Patients performed a 7-m back-and-forth walk in a baseline state and with visual and auditory cues. Gait velocity, stride length and cadence were evaluated using a three-dimensional gait analysis system. For speech evaluation, patients read ten sentences in a baseline state and with visual and auditory cues. The time delay of speech initiation, speech rate and the number of repetitions per sentence were quantified. In PDGF patients, the increase in gait velocity positively correlated with the decrease in the time delay of the speech initiation. Also, the increase in the gait velocity and cadence positively correlated with the decrease in the number of repetitions per sentence. The increase in the stride length positively correlated with the increase in speech rate. Lastly, the increase in stride length positively correlated with the decrease in the number of repetitions per sentence. These findings suggest that there is a common pathomechanism of gait freezing and speech disturbance in PD. Keywords Freezing of gait Parkinson s disease Speech Visual cue Auditory cue Introduction Freezing of gait (FOG) is one of the major disabling features of Parkinson s disease (PD), and is a phenomenon whereby the patients describe feeling glued to the ground. FOG, which is defined as a brief, episodic absence or marked reduction of forward progression of the feet, despite the intention to walk [2], occurs when the patient initiates gait, changes the direction of gait or H. K. Park Department of Neurology, Inje University Ilsan-Paik Hospital, Goyang, Korea H. K. Park M. Kwon J.-H. Lee S. J. Chung (&) Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Pungnap-dong, Songpa-gu, Seoul , Korea sjchung@amc.seoul.kr J. Y. Yoo Department of Rehabilitation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea S. J. Lee Department of Rehabilitation Medicine, Dong-A University of Hospital, Busan Ulsan Regional Cardiocerebrovascular center, Busan, Korea S. R. Kim College of Nursing, Chonbuk National University, Jeonju, Korea M. J. Kim Department of Health Screening and Promotion Center, Asan Medical Center, Seoul, Korea M. C. Lee Department of Neurology, Cheongshim International Medical Center, Gapyeong-gun, Korea S. M. Lee Department of Electronic Engineering, Inha University, Incheon, Korea

2 358 Neurol Sci (2014) 35: changes the speed of gait [1]. Patients with off freezing may respond to levodopa, but patients with on freezing usually do not respond to levodopa or surgery [3]. Speech disturbances in PD are characterized by hypophonia, oral festination, palilalia, and freezing of speech. Freezing of speech has been defined as interruptions of normal flow of speech with pauses and speech arrests [3, 4]. Both FOG and speech disturbances occur more commonly in the late stages of the disease and barely respond to levodopa. Oral festination has been reported to correlate with gait festination [5], and the deprenyl and tocopherol antioxidative therapy of Parkinsonism (DATATOP) study showed a strong association between FOG and speech abnormalities [4]. Recently, Vercruysse et al. [6] demonstrated that non-gait freezing is an independent determinant of FOG. Specifically, freezing episodes while talking were present in 44 % of patients with FOG and 13 % of patients without FOG [6]. FOG and speech dysfluency are both axial symptoms of PD and may be closely related [2, 7]. While only a small number of studies have reported a direct correlation between gait and speech in PD [4, 5, 7, 8], there has not been a study that has reported the relation between the changes in gait and speech parameters using sensory cues. Sensory cues may improve focused attention and aid gait prioritization [9] and can help patients overcome FOG by allowing them to switch from internally triggered movements to externally triggered movements [1]. It has been proposed that activation of the cerebello-parieto-premotor loops underlies the effects of cueing [10]. Dysfunction of the fronto-parietal network, which is a motor control system that uses visual and attentional information, may play a role in the development of FOG [11]. Our aim was to investigate the relation between changes in FOG and speech disturbance elicited by sensory cues in both PD patients with FOG and without FOG to test the hypothesis that there is a relation between the effects of cueing on gait and speech in PD patients with FOG, but not in PD patients without FOG. Materials and methods they showed levodopa-responsive FOG. The diagnosis of PD was defined by the UK Parkinson s Disease Society Brain Bank Clinical Diagnostic Criteria [12]. No patient had secondary Parkinsonism, history of encephalitis, psychiatric disorders, severe systemic illnesses, or cognitive impairment (Korean Mini-Mental State Examination score, K-MMSE \ 24) [15]. The presence of FOG was determined according to the patient s history, scores on the translated version of the Gait and Falls Questionnaire (GFQ) and the Freezing of Gait Questionnaire (FOGQ) [13], and the Unified Parkinson s Disease Rating Scale (UPDRS) score [14]. Informed consent was obtained from all patients who participated in this study which was approved by the Institutional Review Board of Asan Medical Center. The parkinsonian motor features were evaluated using UPDRS part III and Hoehn and Yahr (H&Y) stage [16]. The axial subscore of the UPDRS was defined as the sum of the following UPDRS III items: speech, rising from chair, posture, postural instability, and gait [17]. All patients were evaluated with K-MMSE and Montreal Cognitive Assessment-Korean (MoCA-K) [18]. Gait analysis All gait analyses were performed in an off state, and patients were instructed not to take antiparkinsonian medications for 12 h prior to the tests that were carried out the following morning. At the beginning of the gait session, physical examinations of the pelvis and legs were performed and retroreflective markers were attached to the anterior superior iliac spines, lateral malleolus, heel, forefoot, and sacrum. Patients were instructed to walk backand-forth between two points that were 7 m apart. A threedimensional gait analysis system consisting of six cameras (Motion Analysis Ò, CA, USA) was operated by two rehabilitation specialists. A research nurse was on standby throughout the session to prevent the patient from falling. Patients performed the walk without cueing (baseline), and then with visual and auditory cues. Visual cues consisted of white stripes, 0.5 m long and 100 mm wide, that were placed along the walkway at intervals equivalent to Subjects 19 PD patients with FOG (PDGF) and 11 PD patients without FOG (PDNF) were enrolled in the study. One patient with concurrent developmental stuttering and eleven patients who declined to undergo the experiment for speech analysis were later excluded. Ultimately, 18 patients with PD, including 9 PDGF patients and 9 PDNF patients were enrolled. Seven patients with PDGF showed freezing episodes during the off state. Two patients with PDGF did not show the wearing off phenomenon of freezing during the research period while Fig. 1 Photographs of the visual cues used in gait visual cues consisted of white stripes, 0.5 m long and 100 mm wide, which were placed on the floor along the walkway

3 Neurol Sci (2014) 35: normalized step length (0.8 9 leg length) (Fig. 1) [19]. Auditory cues were provided by a metronome operating at % below cadence in the baseline condition [20]. A neurologist or a specialized nurse evaluated the number of freezing episodes per session, the total number of steps, and the duration of one gait session. The duration of one gait session refers to the length of one gait session. All gait tests were videotaped, and freezing episodes were verified by two neurologists. Spatiotemporal gait parameters (velocity, stride length, and cadence) were quantified from the three-dimensional positions of the retroreflective markers. In one patient with PDGF, severe FOG made it impossible to finish the 7-m walk evaluation. For this patient, spatiotemporal gait parameters were analyzed up until the point at which the patient began to freeze. Speech analysis All speech analyses were performed in an off state. Speech analysis was performed by a speech-language pathologist who was blind to the outcome of the gait analysis using a program designed by the SLP and a specialist in biomedical engineering [21]. Subjects read ten sentences that were balanced for syntactic complexity and length of syllables for each of the following three conditions: baseline (without cues), with visual cues, and with auditory cues. The visual cue was provided by a blue arrow that moved along the sentence from one syllable to the next at 300-ms intervals, which was the lower limit of rate of normal speech [22]. The auditory cue was a programmed sound (500 Hz) that was provided at 300-ms intervals. Both cues disappeared when they reached the blank part between words and re-appeared in the next syllable. The Praat software program ( was used for the analysis of the speech samples. The time delay of speech initiation (the interval from the onset of the program to the initiation of speech), speech rate (number of syllables/s), and dysfluency (number of repetitions/sentence) was measured. When a patient demonstrated repetition of a syllable or phrase within the sentence, the number of repetitions per sentence was evaluated. Statistical analysis p values \ 0.05 were regarded as statistically significant. The Mann Whitney U test was used to compare non-parametric continuous variables, such as education level, MoCA- K score, H&Y stage, UPDRS score, axial subscore of UP- DRS, levodopa dose, score of GFQ, and score of FOGQ between PDGF and PDNF. The Wilcoxon signed-rank test was used to compare parameters of gait and speech between the baseline condition and each cued condition for each patient group. Spearman s correlation coefficient was used to investigate the relations between the changes in gait and speech parameters from the baseline condition to each cued condition for each patient group. Results Baseline demographics There were no significant differences in age, sex, height, weight, education, UPDRS III score, K-MMSE score, and MoCA-K score between PDGF and PDNF patients (Table 1). The PDGF patients had a longer duration of disease, more severe H&Y stage, higher UPDRS II and axial scores, higher scores on both the GFQ and FOGQ, and a higher dose of levodopa (Table 1). Gait analysis In the baseline condition, the total number of steps (p = 0.001) and the duration of one gait session (p \ 0.001), and the number of freezing episodes (p = 0.027) were higher in PDGF patients than in PDNF patients, and velocity (p = 0.019) and stride length (p = 0.024) were lower (Table 2). In PDGF patients, the total number of steps decreased from 74 cm at baseline to Table 1 Demographics of patients with PDGF and PDNF PDGF (n = 9) PDNF (n = 9) p value Sex (M/F) 7/2 5/ Age (years) 66.7 ± ± Height (cm) ± ± Weight (kg) 62.7 ± ± K-MMSE score 26.8 ± ± Disease duration (years) 8.3 ± ± * H&Y stage 2.2 ± ± UPDRS II score 12.9 ± ± * UPDRS freezing score 2.8 ± ± 0.3 \0.001* UPDRS III score 17.2 ± ± UPDRS axial subscore 4.2 ± ± * Education level (years) 10.1 ± ± MoCA-K score 24.2 ± ± Levodopa dose (mg) ± ± GFQ score 34.8 ± ± 3.3 \0.001* FOGQ score 15.6 ± ± 1.9 \0.001* Data are the mean ± standard deviation M/F male/female, PDGF Parkinson s disease patients with gait freezing, PDNF Parkinson s disease patients without gait freezing, UPDRS unified Parkinson s disease rating scale, H and Y stage Hoehn & Yahr stage, K-MMSE Korean Mini-Mental State Examination, MoCA-K Montreal Cognitive Assessment-Korean, GFQ gait and falls questionnaire, FOGQ freezing of gait questionnaire * p \ 0.05

4 360 Neurol Sci (2014) 35: cm with visual cues (p = 0.012) and stride length increased from 70.4 cm at baseline to 93.3 cm with visual cues (p = 0.038); however, there was no effect of auditory cues on any parameter in PDGF. In PDNF patients, the velocity decreased from cm/s at baseline to 96.4 cm/ s with visual cues (p = 0.021). In PDNF, with the auditory cue, cadence decreased from to steps/min (p = 0.012). Speech analysis There was no difference in the time delay of speech initiation between at baseline and that with the visual or the auditory cues in either PDGF or PDNF patients. In PDGF patients, the speech rate was lower with the visual cues (p = 0.008) and with the auditory cues (p = 0.008) than at baseline, and the number of repetitions per sentence was lower with the auditory cues (p = 0.012) than at baseline (Table 2). In PDNF patients, the speech rate was lower with the visual cues (p = 0.008) and with the auditory cue (p = 0.008) than at baseline (Table 2.). Correlation analysis In PDNF patients, there were no significant correlations between the change in any gait parameters and the change in any speech parameter. By contrast, in PDGF patients, there were correlations between the change in gait and speech parameters. The increase in gait velocity with the visual cues was positively correlated with the decrease in the time delay of the speech initiation with the auditory cues (r = 0.817, p = 0.007; Fig. 2a). The gait velocity (r = 0.854, p = 0.003) and cadence (r = 0.686, p = 0.041) after the auditory cues were positively correlated with the decrease in the number of repetitions with the visual cues (Fig. 2b, c). The increase in stride length with visual cues was positively correlated with the increase in speech rate after the auditory cues (r = 0.717, p = 0.030; Fig. 2d), and the increase in stride length with the auditory cues was positively correlated with the decrease in the number of repetitions per sentence with the auditory cues (r = 0.750, p = 0.020; Fig. 2e). Discussion The results of this study demonstrate that changes in gait velocity, cadence, and stride length using sensory cues correlated with changes in the time delay of speech initiation, the speech rate, and the number of repetitions per sentence in PDGF patients, but not in PDNF patients. These findings are in accordance with previous reports [4, 5, 7], and support the hypothesis that gait and speech dysfunctions in PD may share a similar pathophysiological process. The DATATOP study demonstrated that the development of FOG was associated with speech problems at the baseline [4], and Moreau et al. reported a high correlation between oral festination and gait festination [21]. Cantiniaux et al. showed large similarities between the gait pattern and speech dysfunction in PD patients undergoing deep brain stimulation of the subthalamic nucleus [7]. However, there are no previous studies that have investigated the differences in gait and speech abnormalities between PDGF patients and PDNF patients. In this study, we demonstrated a difference in the relation between changes in gait and speech parameters elicited by sensory cues in PD patients according to the presence or absence of Table 2 The cueing effect of gait and speech in Parkinson s disease patients with (PDGF) and without (PDNF) freezing PDGF PDNF Baseline VC AC Baseline VC AC Gait Number of steps 73.9 ± ± 3.6* 55.1 ± ± ± ± 2.9 The duration of one gait session (s) 51.9 ± ± ± ± ± ± 2.0 Number of freezes 5.5 ± ± ± Velocity (cm/s) 67.5 ± ± ± ± ± 12.1* ± 12.4 Cadence (steps/min) ± ± ± ± ± ± 4.7* Stride length (cm) 70.4 ± ± 15.9* 72.8 ± ± ± ± 11.5 Speech Initiation time (s) 1.4 ± ± ± ± ± ± 0.1 Speech rate (no. of syllables/s) 5.2 ± ± 0.3* 2.6 ± 0.0* 4.9 ± ± 0.8* 2.6 ± 0.1* Dysfluency (no. of repetition/sentence) 0.6 ± ± ± 0.2* 0.2 ± ± ± 0.1 Data are the mean ± standard deviation PDF Parkinson s disease patients with freezing, PDNF Parkinson s disease patients without gait freezing, VC visual cue condition, AC auditory cue condition, sec. seconds, No. number * p \ 0.05 compared to baseline value

5 Neurol Sci (2014) 35: Fig. 2 Significant correlations between changes in gait and speech parameters in Parkinson s disease patients with freezing of gait. a The relation between the changes in gait velocity from baseline to visual cue conditions and the changes in the time delay of speech initiation from baseline to auditory cue conditions. b The relation between the change in gait velocity from baseline to auditory cue conditions and the change in the number of repetitions per sentence of speech from baseline to visual cue conditions. c The relation between the change in gait cadence from baseline to auditory cue conditions and the change in speech rate from baseline to auditory cue conditions. d The relation between the change in stride length from baseline to visual cue conditions and the change in the number of repetitions per sentence of speech from baseline to visual cue conditions. e The relation between the change in stride length from baseline to auditory cue conditions and the change in the number of repetitions per sentence of speech from baseline to auditory cue conditions FOG. This indicates that there may be a common pathogenic mechanism of FOG and speech problems in PD. FOG and speech problems may share a common pathophysiology with disturbances at high levels of motor control, possibly at the supplementary motor area (SMA) [4]. Functional imaging studies have suggested that the posterior sensory association cortices may be involved in dysfunction of the basal ganglia-frontal motor association cortex circuit in PD patients with FOG [23 27]. The specific patterns of atrophy involving the frontal and parietal cortices suggested that executive dysfunctions and perception deficits could contribute to the development of FOG [28]. Cognitive load is considered to be an important factor in the pathophysiology of FOG [29]. Executive dysfunction and impairment of the set-shifting ability indicate that FOG may be associated with dysfunction of the fronto-striatal circuitry [30, 31]. A 2-year follow-up study showed that onstate FOG correlated with a faster progression of executive dysfunctions [32], and perceptual impairment may be an important contributing factor to FOG in PD [33]. In addition, FOG may be a manifestation of the impaired ability to initiate cognitive programs, and cognitive impairment may exacerbate the development of freezing episodes [34]. Impairment of frontal and parietal circuitry is associated with disease progression [35] and cognitive dysfunctions in PD [36], and may play a role in the occurrence of FOG. Our findings on the effects of sensory cues on gait and speech emphasize the critical role of the inferior parietal lobule in the pathomechanism of FOG and speech disturbance. The inferior parietal cortex is involved in the integration of perceptual spatiotemporal information [37] and the attentional shifting that is necessary to maintain simultaneously activated auditory and visual information [38]. The improvement of gait that has been reported after long-term use of visual cues could be due to a change in the

6 362 Neurol Sci (2014) 35: control of gait from the basal ganglia-sma circuit (the internal network) to the cerebellum-parietal cortexpremotor area circuit (the external network) [39, 40]. This study also suggests that sensory information in the parietal association cortex may be commonly involved in the pathogenesis of FOG and speech disturbance through the shifting from the internal network to the external network. We concede that this study has several limitations. First, the number of subjects was limited as it was problematic for patients to perform both gait and speech analyses. Second, in the laboratory setting, it was difficult to elicit FOG and speech problems due to the episodic and unpredictable nature of freezing. In conclusion, we demonstrated an association between gait and speech, specifically in the changes elicited by sensory cues, in patients with PDGF. 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