Good vibrations: tactile cueing for freezing of gait in Parkinson's disease.

BACKGROUND: Cueing strategies can alleviate freezing of gait (FOG) in people with Parkinson's disease (PD). We evaluated tactile cueing delivered via vibrating socks, which has the benefit of not being noticeable to bystanders. OBJECTIVE: To evaluate the effect of tactile cueing compared to auditory cueing on FOG. METHODS: Thirty-one persons with PD with FOG performed gait tasks during both ON and OFF state. The effect of open loop and closed loop tactile cueing, as delivered by vibrating socks, was compared to an active control group (auditory cueing) and to a baseline condition (uncued gait). These four conditions were balanced between subjects. Gait tasks were videotaped and annotated for FOG by two experienced raters. Motion data were collected to analyze spatiotemporal gait parameters. Responders were defined as manifesting a relative reduction of > 10% in the percent time frozen compared to uncued gait. RESULTS: The average percent time frozen during uncued gait was 11.2% in ON and 21.5% in OFF state. None of the three tested cueing modalities affected the percentage of time frozen in either the ON (p = 0.20) or OFF state (p = 0.12). The number of FOG episodes and spatiotemporal gait parameters were also not affected. We found that 22 out of 31 subjects responded to cueing, the response to the three types of cueing was highly individual. CONCLUSIONS: Cueing did not improve FOG at the group level; however, tactile as well as auditory cueing improved FOG in many individuals. This highlights the need for a personalized approach when using cueing to treat FOG.

Parkinson's disease patients compensate for balance control asymmetry.

In Parkinson's disease (PD) subtle balance abnormalities can already be detected in early-stage patients. One feature of impaired balance control in PD is asymmetry: one leg produces more corrective joint torque than the other. We hypothesize that in mild to moderately affected PD patients, the least impaired leg compensates for the more impaired leg. Twenty PD patients and eleven healthy matched control subjects participated. Clinical asymmetry was determined by the difference between the left and right body side scores on the Unified Parkinson's Disease Rating Scale. Balance was perturbed with two independent continuous multisine perturbations in the forward-backward direction. Subsequently, we applied closed-loop system identification, which determined the spectral estimate of the stabilizing mechanisms, for each leg. Balance control behavior was similar in PD patients and control subjects at the ankle, but at the hip stiffness was increased. Control subjects exhibited symmetric balance control, but in PD patients the balance contribution of the leg of the clinically least affected body side was higher whereas the leg of the clinically most affected body side contributed less. The ratio between the legs helped to preserve a normal motor output at the ankle. Our results suggest that PD patients compensate for balance control asymmetries by increasing the relative contribution of the leg of their least affected body side. This compensation appears to be successful at the ankle but is accompanied by an increased stiffness at the hip. We discuss the possible implications of these findings for postural stability and fall risk in PD patients.

Event-related mu-rhythm desynchronization during movement observation is impaired in Parkinson's disease.

OBJECTIVE: Patients with Parkinson's disease often experience difficulties in adapting movements and learning alternative movements to compensate for symptoms. Since observation of movement has been demonstrated to lead to the formation of a lasting specific motor memory that resembled that elicited by physical training we hypothesize that mu-rhythm desynchronization in response to movement observation is impaired in Parkinson's disease. METHOD: In a pilot study with nine patients with Parkinson's disease at a Hoehn and Yahr stage of I or II and eleven age-matched controls, we tested this hypothesis by comparing the event related desynchronization (ERD) patterns from the EEG recorded during the observation of hand action and baseline videos. RESULTS: Healthy subjects showed normal bilateral ERD of the mu-rhythm. In patients with Parkinson's disease this distinct ERD pattern was lacking. CONCLUSION: The results of this study suggest that event-related mu-rhythm desynchronization is impaired in Parkinson's disease, even at early stages of the disease. SIGNIFICANCE: Studying event-related mu-rhythm desynchronization dysfunction in Parkinson's disease patients may enhance our understanding of symptoms as impaired motor learning.

Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial.

BACKGROUND: Sialorrhea affects approximately 75% of patients with Parkinson disease (PD). Sialorrhea is often treated with anticholinergics, but central side effects limit their usefulness. Glycopyrrolate (glycopyrronium bromide) is an anticholinergic drug with a quaternary ammonium structure not able to cross the blood-brain barrier in considerable amounts. Therefore, glycopyrrolate exhibits minimal central side effects, which may be an advantage in patients with PD, of whom a significant portion already experience cognitive deficits. OBJECTIVE: To determine the efficacy and safety of glycopyrrolate in the treatment of sialorrhea in patients with PD. METHODS: We conducted a 4-week, randomized, double-blind, placebo-controlled, crossover trial with oral glycopyrrolate 1 mg 3 times daily in 23 patients with PD. The severity of the sialorrhea was scored on a daily basis by the patients or a caregiver with a sialorrhea scoring scale ranging from 1 (no sialorrhea) to 9 (profuse sialorrhea). RESULTS: The mean (SD) sialorrhea score improved from 4.6 (1.7) with placebo to 3.8 (1.6) with glycopyrrolate (p = 0.011). Nine patients (39.1%) with glycopyrrolate had a clinically relevant improvement of at least 30% vs 1 patient (4.3%) with placebo (p = 0.021). There were no significant differences in adverse events between glycopyrrolate and placebo treatment. CONCLUSIONS: Oral glycopyrrolate 1 mg 3 times daily is an effective and safe therapy for sialorrhea in Parkinson disease. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that glycopyrrolate 1 mg 3 times daily is more effective than placebo in reducing sialorrhea in patients with Parkinson disease during a 4-week study.

Detecting asymmetries in balance control with system identification: first experimental results from Parkinson patients.

Cognitive processes can influence balance in various ways, but not all changes in postural performance can easily be identified with the naked clinical eye. Various studies have shown that dynamic posturography is able to detect more subtle changes in balance control. For patients with Parkinson's disease (which is typically an asymmetric disease), changes in the symmetry of balance control might provide a sensitive measure of cognitive influences on balance. Here, we describe a new posturography technique that combines dynamic platform perturbations with system identification techniques to detect such asymmetries in balance control of two patients with Parkinson's disease. Results were compared to those of six healthy controls. Our pilot data show clear asymmetries in dynamic balance control, even though patients themselves were not aware of this and had no subjective problems with stability or standing. We also found asymmetries in weight bearing, but the asymmetries in dynamic balance contribution were larger. Finally, asymmetries in weight bearing and dynamic balance in patients were not tightly coupled as in healthy controls. Future studies could incorporate this approach when examining the influence of mental decline on postural regulation.

Impaired antagonist inhibition may contribute to akinesia and bradykinesia in Huntington's disease.

OBJECTIVE: To test the hypothesis that besides impaired agonist facilitation, impaired antagonist inhibition also contributes to delayed initiation (akinesia) and slow execution (bradykinesia) of voluntary movements in Huntington's disease. METHODS: Fifteen patients with Huntington's disease and 11 age-matched controls participated in the study. The amount of agonist facilitation was measured as the increase in soleus H-reflex amplitude prior to ballistic voluntary plantar flexion (soleus contraction). Antagonist inhibition was measured as the decrease in soleus H-reflex prior to ballistic dorsiflexion (tibialis anterior (TA) contraction). The amount of agonist facilitation and antagonist inhibition was correlated with the time needed for motor initiation (reaction time) and movement execution (movement time). RESULTS: Starting 50ms prior to soleus contraction, soleus H-reflex increased in control subjects but less so in patients. Soleus H-reflexes decreased in controls 25ms prior to TA contraction, while this antagonist inhibition was completely lacking in patients. Thus, patients with Huntington's disease not only displayed reduced agonist facilitation, but impaired antagonist inhibition as well. Moreover, more impairment of antagonist inhibition correlated significantly with more severe akinesia and bradykinesia. CONCLUSIONS: Antagonist inhibition prior to and during agonist contractions is markedly impaired in Huntington's disease. This impairment might contribute to motor slowness in these patients.

Quantitative assessment of daytime motor activity provides a responsive measure of functional decline in patients with Huntington's disease.

Voluntary motor impairment is a functionally important aspect of Huntington's disease (HD). Therefore, quantitative assessment of disturbed voluntary movement might be important in follow-up. We investigated the relation between quantitatively assessed daytime motor activity and symptom severity in HD and evaluated whether assessment of daytime motor activity is a responsive measure in the follow-up of patients. Sixty-four consecutive HD patients and 67 age- and sex-matched healthy controls were studied. Daytime motor activity was recorded using a wrist-worn activity monitor that counts all movements during a period of five consecutive days. Patients were rated clinically for voluntary motor impairment, dyskinesias, posture & gait, depression, cognitive impairment and functional capacity. Follow-up was available from 40 patients (mean follow-up 2.0 years) and 29 controls (mean follow-up 5.9 years). Despite chorea, patients had less daytime motor activity than controls (P < 0.005). This hypokinesia correlated with impaired voluntary movements (r = 0.37; P < 0.01), disturbed posture & gait (r = 0.38; P < 0.005) and especially with reduced functional capacity (r = 0.51; P < 0.0005). During follow-up, hypokinesia remained unchanged in clinically stable patients, but became worse in those whose functional disability progressed (P < 0.005). Hypokinesia seems a core symptom of HD which is related to functional capacity. Actimetric assessment of hypokinesia is responsive to disease progression and can be used as an objective tool for follow-up.

A convenient method to reduce crosstalk in surface EMG. Cobb Award-winning article, 2001.

OBJECTIVES: Crosstalk in surface EMG can be reduced by the use of spatial filters. We compared a variety of spatial filters to establish the most effective and the least complex method to reduce crosstalk. METHODS: Six different spatial filters described in the literature were tested in 8 healthy volunteers. Electrode arrays were placed over the anterior tibial and triceps surae muscles. Selective muscle activation was achieved both by supramaximal nerve stimulation and by maximal voluntary contraction. Selectivity of activation was guaranteed by using intramuscular wire electrodes. Crosstalk was quantified by dividing the amount of EMG activity recorded during pure agonist activation (i.e. the muscle directly under the electrode array) by the EMG activity recorded during pure antagonist activation. This was done for both compound muscle action potentials and voluntary muscle activation. The amount of crosstalk recorded with the different spatial filters was compared with that recorded with a standard bipolar lead. RESULTS: Crosstalk was most reduced by the "double-differential" (DD) filter, yielding an up to 6-fold improvement of EMG selectivity. We then compared signals recorded with this DD filter with those recorded with the less complex "branched electrode". As expected on theoretical grounds, signals from both filter types were identical. CONCLUSIONS: Crosstalk is best reduced using a "double-differentiating" recording technique, which can be achieved easily using a branched electrode instead of a standard bipolar lead. This technique can be used with all conventional EMG equipment.

Unified Huntington's disease rating scale: a follow up.

An objective assessment of the clinical findings in patients with Huntington's disease (HD) is necessary for an evaluation of the longitudinal progression of the disease features. The Unified Huntington's Disease Rating Scale (UHDRS) is a scale to assess clinical performance and functional capacity. The authors examined the 1-year change in UHDRS scores in 78 patients with HD examined either in Leiden, the Netherlands (24 men, 25 women), or in Rochester, New York, United States (12 men, 17 women). A significant decline was seen in motor function, measured with the total motor scale. The total dystonia score increased significantly; the total chorea score did not. The frequency of behavioral disorders tended to increase. The scores on independence scale, functional assessment, total functional capacity, and symbol digit decreased significantly. No relation was observed between the UHDRS items and the age at onset or duration of illness. Thirteen patients with 2-year follow up showed a clear increase in score on the total motor scale and a decline on the independence scale and in total functional capacity. The UHDRS may also be used as a tool for determining therapeutic intervention. Annual evaluation of the total motor scale in every patient gives a clear description of the motor progression of the disease. The authors suggest performing a total UHDRS evaluation every second year for every HD patient as part of the routine longitudinal evaluation.

Habituation of lower leg stretch responses in Parkinson's disease.

In young healthy subjects, initially large stretch responses in leg muscles are progressively attenuated following a series of identical postural perturbations. We have studied whether this habituation of stretch responses is impaired in Parkinson's disease. Ten patients and 10 elderly controls received 10 serial 'toe-up' rotational perturbations (amplitude 10 degrees) while standing on a supporting forceplate. We recorded posturally destabilizing medium latency (ML) stretch responses from the medial gastrocnemius muscle. Functional habituation across the first few trials occurred in patients, but not in elderly controls. The rate of habituation was influenced by the size of the response to the first perturbation. This observation explained the absence of habituation in elderly subjects because their responses during the first few trials were much smaller compared to patients. These results suggest that habituation of lower leg stretch responses is unimpaired in Parkinson's disease. The presence of initially large and 'unpracticed' responses may partially explain why Parkinson patients fall in response to unexpected postural disturbances that commonly occur in daily life.

Clozapine versus placebo in Huntington's disease: a double blind randomised comparative study.

OBJECTIVES: To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease. METHODS: Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately. RESULTS: Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties. CONCLUSIONS: Clozapine has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group.

A shortened version of the motor section of the Unified Huntington's Disease Rating Scale.

Objective assessment of clinical findings of patients with Huntington's disease (HD) is necessary for an evaluation of the individual progression of the disease and the effect of therapy, and it requires specific assessment scales. The Unified Huntington's Disease Rating Scale (UHDRS) is an overall scale to assess clinical performance and functional capacity. In the course of carrying out studies in HD, several items in the motor function section were found to be difficult to score, had high cognitive loading, and appeared to be redundant. The objective of the study was to shorten the motor section of the UHDRS to the smallest number of items, without loss of internal consistency, while still assessing the important clinical features of HD. Shortening the total motor score of the UHDRS was carried out on the UHDRS data set of the Leiden University Hospital using four methods. The first two methods employed principal-component analysis with Varimax rotation. Strongly interrelated test items were uncovered, resulting in a reduction of test items to a smaller set. The third method reduced items so that the internal consistency (Cronbach's alpha) was maximal. The fourth method omitted items subjectively. The results of the Dutch data set were validated on follow-up data and on a data set from the University of Rochester Medical Center, New York. This study determined that the number of items in the motor function section could be reduced from 31 to 15. The reduced set maintains the relationships between the motor and other sections of the UHDRS and still assesses the major clinical features of HD.

Hypokinesia in Huntington's disease.

Motor activity was quantitatively assessed over a period of 5 days using a wrist-worn activity monitor in 14 patients with Huntington's disease (of whom 4 used neuroleptic drugs) and 14 age- and sex-matched healthy controls. Additionally, patients were rated for dementia, depression, clinical impairment of motor tasks, chorea, and disability. A significant decrease in daytime motor activity was observed in patients compared with controls, suggesting hypokinesia rather than hyperkinesia. Hypokinesia tended to be more severe in patients using neuroleptic drugs. Lower activity levels were significantly related to lower scores of functional disability, but not to other clinical measures. We conclude that hypokinesia is a prominent manifestation in Huntington's disease that is worsened by the use of neuroleptics.

Long latency postural reflexes are under supraspinal dopaminergic control.

Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by "toe-up" rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild parkinsonism), 8 patients with young-onset Parkinson's disease, and 4 patients with MPTP-induced parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable) perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a "default" response emerged that anticipated the 10 degrees perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic-induced parkinsonism and young-onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP-induced parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.