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Objective: Examine the level of intra- and inter-limb coherency in non-dyskinetic and dyskinetic patients with Parkinson's disease (PD)., Patients & Methods: Using a magnetic tracking system, whole-body 3D movements were assessed in 10 dyskinetic patients with clear monophasic peak-dose levodopa-induced dyskinesia (LID), in 10 non-dyskinetic patients and in 10 control subjects, standing with their arms out. Patients were tested during their best ON period. Coherency in the kinematics of pairs of body segments was assessed by spectral analysis. For each pair examined, we calculated the highest coherency between 0.5 and 3.0Hz and the frequency at which this maximum coherency occurred., Results: Analysis of variance showed that for 34 out of the 44 (77.3%) comparisons we studied, there were significant differences between the means of coherencies of the groups. Typically, the control group had the highest coherency and the patients with LID had the lowest. Patients with LID also tended to have their maximum coherency at higher frequencies than the control and non-dyskinetic patient groups (30 out of 44 comparisons were significant). These trends appeared in all types of inter-segment comparisons, including bilaterally symmetric segments, biomechanically linked segments (in which coherencies were higher overall in all groups, but still different between groups) and in other comparisons, but the trends were not so clear for comparisons involving the feet., Conclusion: LID is indeed incoherent in the frequency domain, suggesting that body segments may be driven by different neural outputs. The challenges of dealing with these incoherent involuntary movements when planning and executing voluntary movements must certainly play a role in motor difficulties observed in patients with LID. The fact that both dyskinetic and non-dyskinetic patients showed less coherency than controls suggests that levodopa may alter postural control by decreasing stiffness and increasing limb independence., (Copyright 2010 Elsevier B.V. All rights reserved.)

This paper reviews the epidemiology, pathophysiology, clinical features and rationale for managing dyskinesias associated with Parkinson's disease. These are a common clinical problem occurring in up to 90% of patients and more frequently affect those with early-onset. Dyskinesias have a negative impact on quality of life and are an important cause of disability. Their precise etiology is still poorly understood, although it is recognized that dopaminergic pre-synaptic and post-synaptic mechanisms are involved together with extra-dopaminergic factors. The phenomenology of dyskinesias encompasses a variable mixture of two prevalent features: dystonia and chorea. We have studied their time course following a single acute levodopa challenge and have found that dystonia occurs throughout the duration of the on period, whereas choreiform movements occur only at the peak of therapeutic dopaminergic motor responses. This allows a schematic relationship to be drawn between a short duration motor response and the occurrence of dystonia and chorea. There is currently no satisfactory treatment for dyskinesias. Managing the therapeutic window does not provide an adequate solution due to the appearance of a dyskinesia threshold dose that narrows the therapeutic margin. High frequency stimulation of the subthalamic nucleus probably has some specific anti-dyskinetic action, but is limited by the small number of patients who are candidates for this treatment. Research efforts are currently focused on the development of specific anti-dyskinetic medications. Their availability will certainly change the current clinical practice and will widen again the therapeutic window of dopaminergic medications that has now become too narrow.

We examined the clinical features of familial (n = 26) and sporadic (n = 52) Parkinson's disease (PD) in patients presenting over the age of 40 years. Familial PD cases were tested for alpha-synuclein or parkin mutations as appropriate. No mutations were found in any of the families investigated. We found no between-group differences in the age at onset of PD, the pattern or severity of parkinsonian features, the dose of antiparkinsonian medications or treatment related complications. Cases of familial and sporadic PD in our cohort of patients display similar clinical features. This may suggest similar etiologies for both familial and sporadic PD., (Copyright 2003 Elsevier Science Ltd.)

Lesioning of the internal pallidum is known to improve the symptoms of idiopathic Parkinson's disease (PD) and alleviate dyskinesia and motor fluctuations related to levodopa therapy. The benefit obtained contralateral to a single lesion is insufficient in some cases when symptoms are bilaterally disabling. However, reports of unacceptably high rates of adverse effects after bilateral pallidotomy have limited its use in such cases. We report on the outcome of unilateral (UPVP) and bilateral (BPVP) posteroventral pallidotomy in a consecutive case series of 115 patients with PD in the United Kingdom and Australia. After 3 months, UPVP resulted in a 27% reduction in the off medication Part III (motor) Unified Parkinson's Disease Rating Scale score and abolition of dyskinesia in 40% of cases. For BPVP, these figures were increased to 31% and 63%, respectively. Follow-up of a smaller group to 12 months found the motor scores to be worsening but benefit to dyskinesia and activities of daily living was maintained. Speech was adversely affected after BPVP, although the change was small in most cases. Unilateral and bilateral pallidotomy can be performed safely without microelectrode localisation. Bilateral pallidotomy appears to be more effective, particularly in reducing dyskinesia; in our experience, the side effects have not been as high as reported by other groups., (Copyright 2002 Movement Disorder Society)

The effect of chronic bilateral high-frequency stimulation of the subthalamic nucleus (STN) on levodopa-induced dyskinaesias was investigated in eight patients with fluctuating Parkinson's disease complicated by functionally disabling off-period dystonia. All of the patients also had severe diphasic and peak-dose chorea, so that it was possible to study the effect of high-frequency stimulation on the different types of levodopa-induced dyskinaesias. Off-period fixed dystonia was reduced by 90% and off-period pain by 66%. After acute levodopa challenge, high-frequency stimulation of the STN reduced diphasic mobile dystonia by 50% and peak-dose choreic dyskinaesias by 30%. The effect of bilateral high-frequency stimulation of the STN on the Unified Parkinson's Disease Rating Scale motor score had the same magnitude as the preoperative effect of levodopa. This allowed the levodopa dose to be reduced by 47%. The combination of reduced medication and continuous high-frequency stimulation of the STN reduced the duration of on-period diphasic and peak-dose dyskinaesias by 52% and the intensity by 68%. Acute high-frequency stimulation of the STN mimics an acute levodopa challenge, concerning both parkinsonism and dyskinaesias, and suppresses off-period dystonia. Increasing the voltage can induce repetitive dystonic dyskinaesias, mimicking diphasic levodopa-induced dyskinaesias. A further increase in voltage leads to a shift from a diphasic-pattern dystonia to a peak-dose pattern choreodystonia. Chronic high-frequency stimulation of the STN also mimics the benefit of levodopa on parkinsonism and improves all kinds of levodopa-induced dyskinaesias to varying degrees. Off-period dystonia, associated with neuronal hyperactivity in the STN is directly affected by stimulation and disappears immediately. The effect of chronic high-frequency stimulation of the STN on diphasic and peak-dose dyskinaesias is more complex and is related directly to the functional inhibition of the STN and indirectly to the replacement of the pulsatile dopaminergic stimulation by continuous functional inhibition of the STN. Chronic high-frequency stimulation of the STN allows a very gradual increase in stimulation parameters with increasing beneficial effect on parkinsonism while reducing the threshold for the elicitation of stimulation-induced dyskinaesias. In parallel with improvement of parkinsonism, the levodopa dose can be gradually decreased. As diphasic dystonic dyskinaesias are improved to a greater degree than peak-dose dyskinaesias, both direct and indirect mechanisms may be involved. Peak-dose choreatic dyskinaesias, associated with little evidence of parkinsonism and thus with low neuronal activity in the STN, are improved, mostly indirectly. Fixed off-period dystonia, mobile diphasic dystonia and peak-dose choreodystonia seem to represent a continuous clinical spectrum reflecting a continuous spectrum of underlying activity patterns of STN neurons.

Inhibitory control of basal ganglia output to thalamocortical projection plays an important role in normal cortical activity in the current model of the basal ganglia motor circuit. Hypokinetic and hyperkinetic movement disorders of basal ganglia origin can be explained by excess or collapse of the basal ganglia output. An abundance of evidence indicates that parkinsonian akinesia results from hyperactivity of the basal ganglia output. Reversal of akinesia by lesions of the internal division of the globus pallidus (GPi) or its excitatory source, the subthalamic nucleus, agrees with this pathological schema. Ballism associated with subthalamic lesions, and dopa-induced dyskinesia are regarded as hyperkinetic disorders resulting from suppressed subthalamopallidal projection. Decreased firing rate in GPi was reported in both disorders. However, pallidotomy has recently been postulated to abolish both ballism and dopa-induced dyskinesia. A possible mechanism for the effect of GPi destruction in these hyperkinetic disorders may be blockade of the generation or conduction of phasic neuronal activities driving choreic movements. Symptomatologically, dystonia has aspects of both hypokinetic and hyperkinetic disorders. Overactivity of the premotor cortices, which receive projections from the basal ganglia via the ventral thalamus, was found both at rest and on movement in idiopathic dystonia. This abnormal cortical activity may arise from underactivity of basal ganglia output; however, the amelioration of dystonia with pallidotomy suggests a complex pathomechanism of the pallidothalamic system in dystonia.

Regional cerebral glucose metabolism (rCMRGlu-18FDG) was measured in 6 cases with rigid type Parkinson's disease (PD) (2 cases with dopa-induced dyskinesia = DID), 6 cases with chorea (Ch), 5 cases with essential tremor (EssT) and 2 cases with normal subjects (N). The effects of L-Dopa on rCMRGlu was studied in 3 cases with PD. With the aid of depth microrecording study, stereotactic pallidotomy was performed in all cases with PD. Thalamotomy was performed in 3 cases with Ch. In the EssT and N group, the metabolic pattern was high in the frontal cortex (FCx) but low in the lenticular nucleus (LN). In contrast, all cases with a rigid type PD showed lower rCMRGlu in FCx (premotor, prefrontal area). However, 4 out of 6 cases were higher in LN than the control group. Administration of L-Dopa shifted rCMRGlu toward the normal pattern in this group. Five out of 6 cases with Ch represented higher rCMRGlu in FCx (3 focal, 2 diffuse) but lower in LN. Moreover, when DID occurred, it showed almost the same pattern as in Ch. Electrophysiological studies showed high background neuronal activity (BNA) in the medial segment of the globus pallidus (GP) but low BNA in the lateral segment of the GP in the rigid type of PD. In cases with Ch, irregular burst discharges were often encountered in ventro-oral thalamus. From these results, the on-going changes of basal ganglia-thalamocortical motor circuit in cases with a rigid type PD, DID and Ch are discussed. The underlying mechanisms of Parkinsonian rigidity was considered to contrast with those of DID and Ch within the same motor circuit.

We compared the regularity of involuntary muscle contractions in patients with Huntington's disease, vascular chorea, hemiballism and parkinsonian tremor to clarify the nature of phasic involuntary movements caused by lesions in the basal ganglia. Rectified and smoothed electromyograms (EMGs) in involuntary contractions of the predominantly affected muscles were analyzed. After detecting the muscle whose EMG waves showed the most regular rhythm, the frequency, coefficients of variation of interval, amplitude and rise time of the successive EMG waves were compared. The regularity of the intervals of the EMG waves in vascular chorea was significantly greater than that in Huntington's chorea, and some patients with vascular chorea showed a regular rhythm the degree of which approximated that of parkinsonian tremor. The regularity of the intervals of the EMG waves in hemiballism was greater than that in Huntington's chorea, but lower than that in vascular chorea. The regularities of interval, amplitude and rise time all showed the same ordering across the patient groups. The high regularity of muscle contraction intervals in vascular chorea and hemiballism may arise from neural circuits that are abnormally activated as well as those producing tremor.

The aim of this study was to provide further insight into the phenomenology and pathophysiology of monophasic and biphasic dyskinesias induced by levodopa in Parkinson's disease. For this purpose, the type, localization, severity, and timing of dyskinesias were evaluated in 15 parkinsonian patients in relation to motor disability after administration of levodopa using a video-electromyographic recording device. Foot-dystonia, myoclonus, and akathisia were observed in most patients. The dyskinesias started in the foot, usually on the side most affected by the disease, and spread in an "ascending wave" to the contralateral side, the trunk, and upper extremities. In a few patients, onset was axial, spreading almost instantaneously to all limbs. The dyskinesias were dystonic and ballistic at the start, and became increasingly choreic as they attained the upper limbs. Their intensity was maximal in the lower limbs, then progressively decreased, while increasing in upper limbs and head. The results indicate that there is no strict dichotomy between biphasic and monophasic dyskinesias. In other words, there is a "continuum" between the first dyskinesias and those observed during the period of maximal clinical improvement. These dyskinesias can also appear in reverse order, as if there were an "oscillator" determining a sequence of alternating patterns.

Whether the basal ganglia have a cognitive function or not is a worldwide dispute. We have examined 13 parkinsonian patients and 12 age-matched non-parkinsonian controls using the Modified Wisconsin Card Sorting Test (MCST). All 12 controls could achieve all 6 sets of categories which were successively changed. On the other hand, in the parkinsonians, 9 patients could achieve all 6 sets, but 4 patients could do only 4 to 0 sets. The difference between the two groups was statistically significant. These 4 patients who showed poor achievement on MCST had tendency showing higher percentage of perseverative errors. Taking the proportion of perseverative error (PE) to total error (TE) revealed that the parkinsonian group had a peak ranged from 55% to 65% which meant higher occurrence of perseverative errors. When the 4 parkinsonians whose proportion of PE/TE on MCST was over 55% were excluded, a comparison of the parkinsonians with the controls showed no significant difference statistically in both groups. There were no clinical differences based upon Yahr's classification between the 4 parkinsonians with poor MCST score and those with the normal score. Among these parkinsonians whose proportion of PE/TE ranged from 55% to 65%, 3 cases showed apparent frontal lobe signs and 3 mild dementia on Wechsler Intelligence Scale for Adults. Two patients with chorea-acanthocytosis and showing a marked atrophy of the caudate nucleus were also examined. They showed excellent results on MCST.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors describe the application of Akt -30 Aktograf apparatus designed by the branch of the Centre of Medical Technique in Bia ł ystok for recording extrapyramidal involuntary movements, cerebellar dyssynergia and clonic movements.