Coordination and control of forces during multifingered grasping in Parkinson's disease

In this study, we focused on how subjects with Parkinson's disease (PD) grasp and lift with five-digits of the hand. This task provided the opportunity to simultaneously examine (a) the coordination of multiple segments (i.e., digits), (b) the sequencing of multiple tasks (i.e., force development, object lift, and hold), and (c) the control of force output. We found that PD patients coordinated and controlled five-digit forces comparable to that of age-matched controls. Specifically, these groups developed and maintained similar force amplitudes and force sharing patterns across all grasping phases. In addition, PD patients demonstrated similar levels of variability both within and across trials. In the frequency domain, however, some differences were observed across groups, especially in PD patients exhibiting obvious action tremor (AT) at a single modal frequency. In these subjects (four of nine PD patients), there was a systematic disruption, i.e., a phase-shifting away from approximately 0 degrees, in-phase force synchronization patterns normally observed between digits. This disruption typically occurred at and around the AT frequency, while at many other frequencies synchronization patterns were maintained. The composite of these findings implies that although global features observed in five-digit grasping in PD patients are preserved, more subtle aspects of the coordination between digits, as revealed by frequency domain analysis, are not. These results are discussed in relation to the neural mechanisms that might underlie physiological synchronization of forces and its pathological disruption.     

Head tremor in dentatorubral-pallidoluysian atrophy

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal-dominant neurodegenerative disorder characterized by variable combination of clinical manifestations including ataxia, myoclonus, seizures, dementia, and choreic movements. Head tremor has been rarely reported. We report a 66-year-old-woman with genetically determined DRPLA who presented with head tremor. A "no-no" type head tremor was the initial and the most prominent symptom, and mild cerebellar signs and choreic movements were also observed later. Neither hand tremor nor dystonia was noted. The patient did not show dementia, myoclonus, or seizures. Surface electromyogram (EMG) revealed 3.5-4 Hz rhythmic EMG bursts in both sternocleidomastoid muscles. DNA analysis disclosed expanded trinucleotide repeats (n = 54) in the DRPLA gene. We suggest that isolated head tremor can be a clinical manifestation of DRPLA.     

Muscle loading as a method to isolate the underlying tremor components in essential tremor and Parkinson's disease

Tremor is clinically evaluated and classified on the basis of its response to limb posture (resting, postural, and kinetic tremor), but the mechanisms underlying this powerful influence remain unclear and no satisfactory method exists to identify or quantify underlying tremor subtypes. Postural change is closely linked to changes in gravitational load. We therefore assessed the effect of changes in muscle load on essential tremor (ET) and parkinsonian tremor (PT) independently of postural change. A motor accurately delivered a series of constant (0.2-1.2 Nm) flexion and extension torques about the affected wrist while subjects maintained a constant wrist angle by isometrically contracting wrist flexors or extensors against the applied loads. Linear regression of tremulous electromyogram (EMG) spectral peak amplitude against the applied loads estimated the magnitudes of the load-dependent (LDT) and load-independent (LIT) tremor components. The amplitude of ET was linearly related to increase in gravitational load. It thus contained a large LDT component and a small or absent LIT component. Muscle loading revealed significant LDT and LIT components in PT. LIT was dominant at zero load (classic rest tremor) but both components were present during loading (classic postural tremor). Muscle loading more clearly identifies tremor subtypes than postural effects alone. The method could be applied in clinical and pathophysiological studies.     

Tuned vibration absorber for suppression of rest tremor in Parkinson's disease

A simple approach for the suppression of the tremor associated with Parkinson's disease is presented. The proposed system is a tuned vibration absorber (TVA), which has been very effective in the suppression of vibrations in an experimental model of the human arm with two degrees of freedom. Theoretical and numerical methods were used to study the behaviour of the arm model and to develop an effective tremor reduction approach. Based on these studies, a vibration absorber was designed, tested numerically and fabricated for experimental testing. Expermental investigations indicated that optimum control performance was related to the position of the controller and the excitation frequency. With a distance of 160 mm from the end of forearm, the TVA was found to have the best performance, and, for different tremor frequencies, the vibration of the experimental model was reduced by more than 80%.     

Transient arrest of psychogenic tremor induced by contralateral ballistic movements

One of the clinical characteristics of psychogenic tremors (PT) is the disruption or transient cessation of tremor with distractive manoeuvres, including those involving the performance of voluntary movements with the contralateral hand. Seven patients with PT, 11 patients with Parkinson's disease (PD), 10 patients with essential tremor (ET) and 10 normal volunteers mimicking tremor (NV) were requested to perform a fast unilateral wrist movement to close a switch, at the perception of a visual cue, either at rest or during maintenance of a posture. We measured the time-locked changes in frequency and amplitude occurring in tremor oscillations of the contralateral hand. The reaction time task induced a significant reduction in amplitude or cessation of contralateral tremor oscillations in PT and NV, but not in PD and ET. The effect occurred with a delay with respect to the onset of the contralateral movement without significant differences in PT versus NV (p > 0.05). The physiological mechanisms accounting for the effect seen on tremor of NV and PT may involve the interhemispheric inhibition that accompanies the execution of a unilateral motor task. Tremor circuits in patients with PD and ET may be impervious to these inhibitory commands. The documentation and quantitation of the effects of a ballistic movement on contralateral rhythmic activity are of clinical relevance for the identification of patients with PT.     

Tremor is associated with PET measures of nigrostriatal dopamine function in MPTP-lesioned monkeys

Unilateral intracarotid artery (ICA) MPTP infusion, along with sequential systemic doses of MPTP, produces near complete degeneration of the nigrostriatal pathway on the side of infusion (ipsilateral) and variable levels of damage in the contralateral hemisphere accompanied by varying levels of parkinsonism (overlesioned hemiparkinsonian model). Positron emission tomography and the dopamine (DA) metabolism tracer [(18)F]6-fluoro-l-m-tyrosine (FMT) were used to evaluate the relationship between DA metabolism and clinical features of parkinsonism in 14 overlesioned hemiparkinsonian monkeys. Monkeys were rated on a parkinsonian scale that included ratings of bradykinesia, fine motor skills (FMS), and rest tremor. Because the monkeys tended to show more severe clinical signs on the side of the body contralateral to ICA MPTP infusion, we calculated asymmetry scores for each of the clinical features as well as for FMT uptake (K(i)) in the caudate and putamen. Tremor asymmetry was associated with FMT uptake asymmetry in the putamen. No such relationship was observed for FMS or bradykinesia. The overall severity of tremor (mild, moderate/severe) was associated with FMT uptake in the caudate and putamen. Postmortem biochemical analysis for a subset of monkeys showed that the monkeys with moderate/severe tremor had significantly lower DA levels in both caudate and putamen than those with mild tremor. In addition, K(i) values were significantly correlated with DA levels in both caudate and putamen. These findings support the idea that nigrostriatal degeneration contributes to rest tremor.     

A functional role for complex gangliosides: motor deficits in GM2/GD2 synthase knockout mice

Although gangliosides are abundant molecular determinants on all vertebrate nerve cells (comprising approximately 1.5% of brain dry weight) their functions have remained obscure. We report that mice engineered to lack a key enzyme in complex ganglioside biosynthesis (GM2/GD2 synthase), and which express only the simple ganglioside molecular species GM3 and GD3, develop significant and progressive behavioral neuropathies, including deficits in reflexes, strength, coordination, and balance. Quantitative indices of motor abilities, applied at 8 and 12 months of age, also revealed progressive gait disorders in complex ganglioside knockout mice compared to controls, including reduced stride length, stride width, and increased hindpaw print length as well as a marked reduction in rearing. Compared to controls, null mutant mice tended to walk in small labored movements. Twelve-month-old complex ganglioside knockout mice also displayed significant incidence of tremor and catalepsy. These comprehensive neurobehavioral studies establish an essential role for complex gangliosides in the maintenance of normal neural physiology in mice, consistent with a role in maintaining axons and myelin (Sheikh, K. A. , J. Sun, Y. Liu, H. Kawai, T. O. Crawford, R. L. Proia, J. W. Griffin, and R. L. Schnaar. 1999. Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects. Proc. Natl. Acad. Sci. USA 96: 7532-7537), and may provide insights into the mechanisms underlying certain neural degenerative diseases.     

Effectiveness of the Kampo kami-shoyo-san (TJ-24) for tremor of antipsychotic-induced parkinsonism

The aim of the present study was to evaluate the effectiveness of the Kampo medication kamishoyo-san against tremor due to antipsychotic-induced parkinsonism. Kami-shoyo-san consists of several medicinal herbs that are known in traditional Chinese medicine to be effective in treating Parkinson's disease and convulsions. We gave kami-shoyo-san to eight patients at Higashiowari National Hospital who were exhibiting tremor, a symptom of antipsychotic-induced parkinsonism. The tremor was evaluated on a five-point scale before and after the administration of kamishoyo-san, and the findings were compared statistically. The results showed a stastistically significant reduction in the tremor after the administration of kami-shoyo-san (P<0.01), with 62.5% of patients showing an improvement of one point or more. The tremor did not worsen in any of the patients, and none complained of side-effects. Thus, kami-shoyo-san appears to be effective against the tremor from parkinsonism. Kami-shoyo-san consists of 10 medicinal herbs, including Radix Bulpleuri, Radix Paeoniae, Radix Angelicae Sinensis, and Radix Glycyrrhizae, which are effective in treating disturbances in muscular movement according to TCM theory. Of the 10 herbs contained in kami-shoyo-san, we believe the abovementioned ones are particularly effective in helping to reduce the tremor associated with parkinsonism.     

Essential tremor: an overdiagnosed condition?

The diagnosis of essential tremor (ET) and its differentiation from other types of tremor is often difficult. In 1994 Bain et al. defined a classical phenotype by studying 20 patients with pure essential tremor and similarly affected family members in at least three generations. We assessed how many of the patients diagnosed by different neurologists at our institution as having ET conformed to this defined phenotype. We randomly selected 50 patients who were diagnosed with ET by any neurologist at the National Hospital for Neurology and Neurosurgery since the publication of the Bain et al. report, and determined the number of patients who had clinical features compatible with the phenotype that it had defined. Only 25 (50%) of these patients had ET so defined. Ten patients clearly had alternative diagnoses: four had clear additional dystonia, two neuropathic tremor, two had unilateral leg tremor, one drud-induced tremor, and one sudden onset after head trauma. The remaining 15 patients also had atypical features including myoclonus (one), onset in a body part other than the arms (six), sudden onset (two), rest tremor (seven), onset after the age of 65 years (four), a family member with an isolated head tremor (one), or reduced armswing (two). The diagnosis of ET is overused even among experienced neurologists, and other types of tremor should be considered in atypical patients before making this diagnosis. Received: 30 November 1999 / Received in revised form: 12 May 2000 / Accepted: 21 June 2000