Dyskinetic Patients Research Articles

Levodopa-induced dyskinesias detection based on the complexity of involuntary movements

Complexity of the biological system output reflects the system's ability to adapt in a changing environment. Disease states and aging, which influence the adaptation of biological systems, modify the complexity of system response to environment changes. The alteration of motor adaptivity seen in Parkinson's disease (PD) has never been properly investigated by using the motor response complexity measured with sample entropy. We show here that the differences in the complexity of the involuntary movements can be efficiently used for the discrimination of the PD treatment state (non-dyskinetic/dyskinetic). We studied the complexity in the involuntary movements of three groups of subjects, normal, non-dyskinetic PD, and dyskinetic PD, by using the sample entropy for multiple time-scales. During experiments the subjects were standing with their arms extended in front of them while performing a cognitive task. PD subjects were tested after levodopa administration in their “best” ON condition. For all subject groups we found that the sample entropy increased almost linearly with the increase of the time-scale. The biggest increase was found in the dyskinetic PD and the least in non-dyskinetic PD subjects. This shows that system adaptivity, as revealed by the complexity analysis of postural displacement, is lower than normal in non-dyskinetic PD patients, but is abnormally increased in dyskinetic patients. The clear difference between the sample entropy-based measures for the non-dyskinetic and dyskinetic patients made possible the automatic, efficient recognition of the dyskinetic condition, based on multi-layer perceptrons.

Do dyskinesia and pain share common pathophysiological mechanisms in Parkinson's disease?

Plastic changes within the striatum resulting from pulsatile dopaminergic stimulation are thought to lead to dyskinesia in patients with Parkinson's disease (PD). The basal ganglia play a role in processing pain. We hypothesized that the plastic changes that lead to dyskinesia may also mediate pain responses. Our objective was to compare the change in pain sensitivity after levodopa administration between stable responders, fluctuators without dyskinesia, and dyskinetic patients, and to compare pain sensitivity between PD and healthy subjects. Fifty patients with PD were assessed with cold water immersion after overnight withdrawal of dopaminergic medications and again after a standard levodopa challenge, and carefully classified into stable responder (n = 12), fluctuator (n = 15), and dyskinetic (n = 23) groups. Twenty age-matched controls were also tested. PD patients "off"-medication had a lower threshold (P = 0.016) and tolerance (P < 0.0001) to cold pain compared to controls. After levodopa administration, dyskinetic patients experienced a large increase in cold pain threshold (48%) and tolerance (66%) that was absent in stable responders (P = 0.038 and P = 0.015); there was no significant difference in pain sensitivity change scores between the fluctuator and either the stable responder or dyskinetic groups. Our results suggest that dyskinesia and pain may share common pathophysiological mechanisms in PD.

Diffusion‐weighted imaging and magnetization transfer imaging of tardive and edentulous orodyskinesia

Oral dyskinesias occur in elderly individuals in relation to drug use (tardive dyskinesia, TD) or edentulousness (edentulous orodyskinesia, EOD) but their characterization remains incomplete. Our aim was to investigate whether magnetic resonance techniques such as diffusion-weighted imaging (DWI) and magnetization transfer imaging (MTI) of the brain could be used to differentiate dyskinetic patients from control subjects. Eight drug-treated patients with TD, 12 EOD patients, 8 drug-treated patients without TD, and 10 control subjects were recruited and examined by DWI and MTI. Measurements in the caudate nucleus, putamen, and globus pallidus yielded globally different apparent diffusion coefficient (ADC) values between drug treated patients with TD and control subjects but the magnetization transfer ratios showed no significant variations. The discrimination between dyskinetic patients and control subjects offered by ADC values was however slightly poorer than the discrimination offered by the previously published choline/creatine ratios measured by MR spectroscopy in the basal ganglia. The results are consistent with the pathophysiological hypothesis of damage to cholinergic interneurons.

Relationship between weight, levodopa and dyskinesia: the significance of levodopa dose per kilogram body weight

Levodopa dose per kilogram body weight is reported to be a significant factor for dyskinesia in Parkinson's disease. We have investigated this hypothesis in data from the studies comparing ropinirole versus levodopa as the initial therapy. Data from the ropinirole versus levodopa studies 056 and REAL-PET in early Parkinson's disease were pooled and manipulated to calculate levodopa dose per kilogram body weight. Logistic regression analysis was performed to investigate significant variables for the development of dyskinesia. Only the patients on levodopa monotherapy or with ropinirole were analyzed. Analysis of levodopa therapy patients revealed that dyskinetic patients had received significantly higher absolute levodopa dose and levodopa dose per kilogram body weight. Logistic regression revealed that the most significant factor was the higher levodopa dose per kilogram body weight, P = 0.005, odds ratio 1.078, 95% CI 1.023-1.135; younger age was the second factor -P = 0.026. Variables of gender, absolute levodopa dose, weight, disease duration and initial motor Unified Parkinson's disease rating score were not significant. Higher levodopa dose per kilogram body weight is an independently significant factor for developing dyskinesia. This relationship should be considered in treatment of Parkinson's disease patients aiming to prevent and manage dyskinesia.

Placebo influences on dyskinesia in Parkinson's disease

Clinical features that are prognostic indicators of placebo response among dyskinetic Parkinson's disease patients were determined. Placebo-associated improvements occur in Parkinsonism, but responses in dyskinesia have not been studied. Placebo data from two multicenter studies with identical design comparing sarizotan to placebo for treating dyskinesia were accessed. Sarizotan (2 mg/day) failed to improve dyskinesia compared with placebo, but both treatments improved dyskinesia compared with baseline. Stepwise regression identified baseline characteristics that influenced dyskinesia response to placebo, and these factors were entered into a logistic regression model to quantify their influence on placebo-related dyskinesia improvements and worsening. Because placebo-associated improvements in Parkinsonism have been attributed to heightened dopaminergic activity, we also examined the association between changes in Parkinsonism and dyskinesia. Four hundred eighty-four subjects received placebo treatment; 178 met criteria for placebo-associated dyskinesia improvement and 37 for dyskinesia worsening. Older age, lower baseline Parkinsonism score, and lower total daily levodopa doses were associated with placebo-associated improvement, whereas lower baseline dyskinesia score was associated with placebo-associated worsening. Placebo-associated dyskinesia changes were not correlated with Parkinsonism changes, and all effects in the sarizotan group were statistically explained by the placebo-effect regression model. Dyskinesias are affected by placebo treatment. The absence of correlation between placebo-induced changes in dyskinesia and Parkinsonism argues against a dopaminergic activation mechanism to explain placebo-associated improvements in dyskinesia. The magnitude and variance of placebo-related changes and the factors that influence them can be helpful in the design of future clinical trials of antidyskinetic agents.

Differential gene expression analysis in treatment of Parkinson's disease using the moduli space of triangles

The long-term utility of levodopa (l-dopa) treatmentagainst PD is known to be limited by its subsequentinduction of dyskinesia (l-dopa-induced dyskinesia orLID). Up to now, few treatment strategies have been iden-tified to reverse LID and restore l-dopa efficacy in dyski-netic patients. Among various mechanisms, l-dopasensitization (priming) may play an important role inthe development and maintenance of LID. Disregulationof dopamine (DA) synthesis, release and clearance ofextracellular DA (due to DA neuronal death and conse-quent ectopic synthesis and release by 5-HT terminals)is thought to lead to exaggerated fluctuations in the syn-aptic DA concentrations and consequent neurobiologicalalterations during chronic intermittent l-dopa treatment.These fluctuations, in turn, induce long-term, synapticalterations in the striatum and other brain areas compris-ing the basal ganglia. Previous studies have shown thatlong-term sensitization to cocaine can be reversed byinjecting a dopamine receptor agonist, followed by a 5-HT2 or 5-HT3 antagonist approximately 3.5 hours later[1,2]. To the extent that cocaine addiction may share sim-ilar neurobiological mechanisms with LID, it is reasona-ble to examine a regimen of the DA agonist pergolidefollowed by the 5-HT2 antagonist ketanserin at the peakof acute withdrawal over a treatment period and reversesensitization to l-dopa. Based on our previous finding thatthis specific drug combination regimen can reverse previ-ously-established behavioral and molecular markers ofcocaine or methamphetamine sensitization in rats [3], wedetermined the striatal mRNA expression profiles associ-ated with l-dopa-induced dyskinesia in rats and itsreversal by the pergolide-ketanserin regimen. 6-Hydroxy-dopamine (6-OHDA)-lesioned rats were treated with l-dopa twice a day for 21 days (days 1 – 21) to induceabnormal involuntary movements (AIM), a model of LID.Subsequently, they were treated subcutaneously once aday for 2 weeks with one of the following. Group Areceived pergolide followed by ketanserin; Group Breceived pergolide followed by saline; Group C, the con-trol group, received saline on both occasions. The expres-sion levels of mRNA were measured for 27,342 genes. Thenormalized values provide triplets of positive numbers D= { (

Prevalence and treatment strategies of dyskinesia in patients with Parkinson’s disease

A study into the prevalence and treatment of dyskinesia in Parkinson's disease (PD) patients was performed with 380 PD specialists' completed interviews relating to PD and retrospectively completed 1900 patient record forms for patients with dyskinesia. Physicians reported, that 34% of their PD patients experience dyskinesia, 57% of dyskinetic PD patients were affected by moderately-to-completely disabling dyskinesia. Treatment of dyskinesia was looked upon as not satisfactory, fractionating of levodopa dose was used as first choice therapeutic option of dyskinesia.

The influence of levodopa-induced dyskinesias on manual tracking in patients with Parkinson’s disease

The influence of peak-dose, levodopa-induced dyskinesias (LID) on manual tracking (MT) was examined in 10 dyskinetic patients with Parkinson's disease (DPD), and compared to 10 age/gender-matched non-dyskinetic patients with Parkinson's disease (NDPD) and 10 healthy controls. Whole-body movement (WBM) and MT performance were recorded simultaneously with a 6-degrees-of-freedom magnetic motion tracker and forearm rotation sensors, respectively. Subjects were asked to match the length of a computer-generated line with a line they controlled via wrist rotation. Results show that DPD patients had greater WBM magnitude at rest and during the motor task, both in displacement and in velocity. All groups displayed some increase in WBM displacement from rest to MT, but only the DPD group had a significant increase in WBM velocity during movement. As for MT performance (determined by assessing the positional mismatch between subjects' and target lines), ERROR in displacement was statistically similar between groups. There was no correlation between ERROR and the magnitude of WBM within the DPD group. The DPD group showed significant increased ERROR when the velocity of the subject's line was compared with that of the velocity of the target line. When two distinct target pace segments were examined (FAST/SLOW), no significant differences were found in ERROR for displacement for either group, but both the NDPD and DPD group showed increased ERROR from SLOW to FAST for velocity. This was accompanied with an increase in WBM velocity only in the DPD group. The lack of increased ERROR during the SLOW tracking portion in the DPD group supports the notion that the dyskinesias themselves were not primarily responsible for the ERROR seen in the patients. When examining the positive or negative values of ERROR (i.e., faster or slower than the target), we found that the increased ERROR in velocity observed in the DPD group was the result of excess velocity rather than bradykinesia, manifested as isolated deviations from the target trace in the DPD group that were coherent in time with increased ERROR in velocity. In conclusion, evidence presented in the present study shows that the LID was not the primary cause of the ERROR seen in the DPD group. Accordingly, we propose that the increased ERROR seen in the DPD group resulted from a mechanism distinct from the one generating LID.

Cascade of levodopa dose and weight-related dyskinesia in Parkinson's disease (LD–WD-PD cascade)

We have studied a cohort of 220 Parkinson's disease (PD) patients for risk factors of developing new dyskinesia. Twenty-nine patients were noticed to have developed new dyskinesia at the second assessment. The dyskinetic patients received significantly higher maximum level daily dose of levodopa. These patients had lost weight during the course of the disease from 72±15 to 66±17 kg, p=0.002. The dyskinetic patients received significantly higher daily dose of levodopa per kilogram body weight, 8.4±3.5 mg/kg vs. 6.0±3.9 mg, p=0.003. Weight-losers PD patients developed significantly more dyskinesia than non-weight losers— p=0.002. Logistic regression analysis revealed weight loss and daily levodopa dose per kilogram body weight to be the only significant factors for dyskinesia in addition to disease duration. There was a “dose response to developing dyskinesia” according to the increasing levodopa dose per kilogram body weight.

Bradykinesia in patients with Parkinson's disease having levodopa-induced dyskinesias

We investigated the likelihood that bradykinesia coexisted with levodopa-induced dyskinesias (LID) in 10 dyskinetic Parkinson's disease patients (DPD). Their motor performance was compared to that of 10 age/gender-matched non-dyskinetic patients (NDPD) and 10 healthy controls. Whole-body movement (WBM) and rapid alternating movements (RAM) at the wrist were recorded simultaneously using 6-degree of freedom magnetic motion tracker and forearm rotational sensors, respectively. WBM was recorded prior to, and while subjects performed pronation–supination movements of their dominant hand with maximal rotational excursion, and as fast as possible for 10s. RANGE, VELOCITY and IRREGULARITY of pronation–supination cycles were quantified to assess motor performance. Results show that DPD patients had greater WBM than NDPD and controls during rest and RAM performance, as expected. There were no differences in motor performance between DPD and NDPD groups for RANGE and VELOCITY, despite significantly longer disease duration for the DPD group (15.5 ± 6.2 years versus 6.6 ± 2.6 years). However, both the NDPD and DPD groups showed significantly lower RANGE and reduced VELOCITY compared to controls, suggesting the presence of bradykinesia. For IRREGULARITY, DPD patients showed increased fluctuations in pronation–supination cycle amplitude compared to NDPD and controls. However, the lack of correlation between WBM magnitude and IRREGULARITY within the DPD group (Spearman's rank order, ρ = 0.31, p > 0.05), suggests that LID were not the primary cause of increased IRREGULARITY. In conclusion, our results demonstrated that bradykinesia can coexist with dyskinesias, suggestive of distinct neural circuits. Our results also demonstrated that the occurrence of LID is not inevitably accompanied with worsening of motor performance.

Motor cortex plasticity in Parkinson's disease and levodopa-induced dyskinesias

Experimental models of Parkinson's disease have demonstrated abnormal synaptic plasticity in the corticostriatal system, possibly related to the development of levodopa-induced dyskinesias (LID). We tested the hypothesis that LID in Parkinson's disease is associated with aberrant plasticity in the human motor cortex (M1). We employed the paired associative stimulation (PAS) protocol, an experimental intervention involving transcranial magnetic stimulation (TMS) and median nerve stimulation capable of producing long-term potentiation (LTP) like changes in the sensorimotor system in humans. We studied the more affected side of 16 moderately affected patients with Parkinson's disease (9 dyskinetic, 7 non-dyskinetic) and the dominant side of 9 age-matched healthy controls. Motor-evoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured at baseline before PAS and for up to 60 min (T0, T30 and T60) after PAS in abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. PAS significantly increased MEP size in controls (+74.8% of baseline at T30) but not in patients off medication (T30: +0.07% of baseline in the non-dyskinetic, +27% in the dyskinetic group). Levodopa restored the potentiation of MEP amplitudes by PAS in the non-dyskinetic group (T30: +64.9% of baseline MEP) but not in the dyskinetic group (T30: -9.2% of baseline). PAS prolonged CSP duration in controls. There was a trend towards prolongation of CSP in the non-dyskinetic group off medications but not in the dyskinetic group. Levodopa did not restore CSP prolongation by PAS in the dyskinetic group. Our findings suggest that LTP-like plasticity is deficient in Parkinson's disease off medications and is restored by levodopa in non-dyskinetic but not in dyskinetic patients. Abnormal synaptic plasticity in the motor cortex may play a role in the development of LID.

Neither simple nor sequential arm movements are bradykinetic in parkinsonian patients with peak-dose dyskinesias

Objective To find out whether parkinsonian patients with levodopa-induced peak-dose dyskinesias are bradykinetic. Methods The performance of a sequential internally determined arm movement and a simple externally triggered arm movement was studied in a group of dyskinetic parkinsonian patients during their best clinical condition and when they were OFF treatment. Patients' performance was compared with that of an age-matched control group. Movements in the three-dimensional space were recorded by the ELITE motion analysis system. Kinematic variables analysed for the sequential motor task were total movement duration and total pause duration; for the simple motor task, movement duration and reaction time; and for both tasks, movement inaccuracy. Results When patients were OFF therapy they performed sequential and simple movement tasks slower than healthy subjects whereas when they were dyskinetic they did not. During the sequential task, when the patients were dyskinetic total pause duration shortened and movement inaccuracy increased. Conclusions Our kinematic finding indicates that parkinsonian patients' with peak-dose dyskinesias are not bradykinetic. Significance Parkinsonian patients with peak-dose dyskinesias are not bradykinetic, probably because dopamine at peak doses functionally normalizes the mechanisms controlling movement speed.

Swallowing abnormalities and dyskinesia in Parkinson's disease

Gastrointestinal abnormalities in Parkinson's disease (PD) have been known for almost two centuries, but many aspects concerning their pathophysiology have not been completely clarified. The aim of this study was to characterize the oropharyngeal dynamics in PD patients with and without levodopa-induced dyskinesia. Fifteen dyskinetic, 12 nondyskinetic patients, and a control group were included. Patients were asked about dysphagia and evaluated with the Unified Parkinson's Disease Rating Scale Parts II and III and the Hoehn and Yahr scale. Deglutition was assessed using modified barium swallow with videofluoroscopy. Nondyskinetic patients, but not the dyskinetic ones, showed less oropharyngeal swallowing efficiency (OPSE) for liquid food than controls (Dunnett, P = 0.02). Dyskinetic patients tended to have a greater OPSE than nondyskinetic (Dunnett, P = 0.06). Patients who were using a higher dose of levodopa had a greater OPSE and a trend toward a smaller oral transit time (Pearson's correlation, P = 0.01 and 0.08, respectively). Neither the report of dysphagia nor any of the PD severity parameters correlated to the videofluoroscopic variables. In the current study, dyskinetic patients performed better in swallowing function, which could be explained on the basis of a greater levodopa dose. Our results suggest a role for levodopa in the oral phase of deglutition and confirm that dysphagia is not a good predictor of deglutition alterations in PD.

Increased adenosine A2A receptors in the brain of Parkinson's disease patients with dyskinesias.

Brain adenosine A2A receptors have recently attracted considerable attention because of their interaction with the dopaminergic system and as potential targets for Parkinson's disease pharmacotherapy. Post mortem adenosine A2A receptor mRNA and [3H]SCH 58261- specific binding to adenosine A2A receptor were studied in the brain of Parkinson's disease patients using in situ hybridization and receptor binding autoradiography, respectively. Fourteen levodopa-treated Parkinson's disease patients, of which seven developed dyskinesias and seven did not, were compared with nine controls. Nigrostriatal denervation was similar between dyskinetic and non-dyskinetic Parkinson's disease patients, as assessed with catecholamine concentrations and [125I]RTI-121-specific binding to dopamine transporters. A2A receptor mRNA levels (+129%; P < 0.01) and [3H]SCH 58261-specific binding (+32%, P < 0.01) were increased in the putamen (lateral and medial) of dyskinetic patients compared with controls. The increase of adenosine A2A receptor mRNA in dyskinetic Parkinson's disease patients was also significant compared with non-dyskinetic Parkinson's disease patients (+60%; P < 0.05) in the lateral putamen. Moreover, [3H]SCH 58261-specific binding to adenosine A2A receptors was increased in the external globus pallidus (+24%; P < 0.001) of Parkinson's disease patients compared with controls, regardless of the dyskinesigenic response to levodopa. No change of adenosine A2A receptors was observed in the caudate nucleus, whereas adenosine A2A receptor protein and mRNA levels in the internal globus pallidus were not different from background. These findings suggest that increased synthesis of adenosine A2A receptors in striatopallidal pathway neurons is associated with the development of dyskinesias following long-term levodopa therapy in Parkinson's disease.

Increase of preproenkephalin mRNA levels in the putamen of Parkinson disease patients with levodopa-induced dyskinesias.

The expression of preproenkephalin messenger RNA was studied in the brain of Parkinson disease (PD) patients using in situ hybridization. All these patients were treated with levodopa (LD) and the development of motor complications was recorded. Eleven normal controls and 14 PD patients were used, of which 4 developed dyskinesias, 3 developed wearing-off, 3 developed both dyskinesias and wearing-off, and 4 developed no adverse effect following dopaminomimetic therapy. Nigrostriatal denervation was similar between the subgroups of PD patients as assessed using 125I-RTI-specific binding to the dopamine transporter and measures of catecholamine concentrations by HPLC. A significant increase of preproenkephalin messenger RNA levels was observed in the lateral putamen of dyskinetic patients in comparison to controls (+210%; p < 0.01) and in comparison to nondyskinetic patients (+112%; p < 0.05). No change was observed in medial parts of the putamen or in the caudate nucleus. No relationship between preproenkephalin messenger RNA levels and other clinical variables such as development of wearing-off, age of death, duration of disease, or duration of LD therapy was found. These findings suggest that increase synthesis of preproenkephalin in the medium spiny output neurons of the striatopallidal pathway play a role in the development of dyskinesias following long-term LD therapy in Parkinson disease.

Proprioception in Parkinson's disease is acutely depressed by dopaminergic medications

OBJECTIVESImpaired proprioception has been previously reported in patients with Parkinson's disease. It was hypothesised that dopaminergic medications transiently depress proprioception, with amplification of adventitious movements as a result. This study...

The long-term response to levodopa in dopa-responsive dystonia

We report the long-term response to levodopa in 20 patients with dopa-responsive dystonia (DRD). We found an inverse correlation between the daily dose of levodopa and duration of treatment ( r=−0.59, P<0.01). Mild dyskinesias were present in 20% of our patients. Dyskinetic patients were on a higher dose of levodopa than non-dyskinetics. Dyskinesias responded to a reduction in levodopa, with no deterioration in motor function. We propose that the dopamine turnover might decrease with time, which would lead to a decrease in the requirement for levodopa and the occurrence of dyskinesias late in the course of DRD.

Effects of dopamine metabolites on locomotor activities and on the binding of dopamine: Relevance to the side effects of L-dopa

L-dopa is the major treatment for Parkinson's disease (PD), but its efficacy is limited by the presence of dyskinesia. The dyskinesia develops over a period of exposure to L-dopa and is related to the dosage, therefore, the cause may involve inductive changes that produce toxic levels of metabolites, interfering with dopamine (DA) neurotransmission. Chronic L-dopa induces catechol-O-methyltransferase (COMT) and methionine adenosyl transferase (MAT), enzymes involved in the methylation of catecholamines (CA). In addition, high levels of 3-O-methyl-dopa have been reported in the plasma of dyskinetic PD patients, treated with L-dopa, as compared to non-dyskinetic patients, therefore, the methyl metabolites of CA may be increased during L-dopa therapy and may be involved in the dyskinesia. Since large amounts of DA are produced from L-dopa and DA is extensively methylated, the methyl metabolites of DA, 3-methoxytyramine (3-MT) and 3,4-dimethoxyphenylethylamine (DIMPEA), may be also involved. The first step in knowing this, is to assess the behavioral and DA-receptor activities of 3-MT and DIMPEA. In the rat, the intraventricular injection of 0.5 μM of DIMPEA increased the total distance traveled (TD) by over 100%, the number of movement (NM) made by 40% and the time spent moving (MT) by about 36%. Identical doses of 3-MT decreased the TD by 42%, NM by 22% and MT by 39%. DIMPEA (1 mM) increased the binding of DA with brain membranes by 44.7%, whereas 3-MT decreased it by 15.8%. The results show that 3-MT and DIMPEA are behaviorally active and in parallel, they interact with the binding sites for DA, consequently, they may contribute to the side effects of L-dopa. L-dopa produces high levels of DA and induces MAT and COMT. It is proposed, therefore, that DA will be methylated to 3-MT and 3-MT to DIMPEA. At threshold level each product will inhibit, allosterically, its enzyme of methylation, causing sequential and rhythmic up and down regulation of its concentration. At peak levels these hydrophobic metabolites will modulate the actions of DA on synaptic membranes, causing abnormal movements, at times, resembling the “on-off effects”.

Efficacy of endoventricular patch plasty in large postinfarction akinetic scar and severe left ventricular dysfunction: comparison with a series of large dyskinetic scars

Background: Many believe that dyskinesia is the only predictor of favorable surgical outcome after large myocardial infarction and that akinetic scars do not recover well in patients with globally depressed ventricular function. Methods: This study evaluates clinical and hemodynamic results of endoventricular circular patch plasty in patients with either large akinetic scar ( n = 51) or large dyskinetic scar ( n = 49) and depressed left ventricular function (ejection fraction <30%). Groups were comparable for symptoms, indication for operation, and delay from myocardial infarction. Heart failure was a major indication for operation in both groups. Coronary grafting was performed in 98% of patients: 10 had mitral valve repair or replacement, and 47 patients with preoperative ventricular arrhythmias had cryotherapy. In-hospital mortality was 12% (five patients in the akinetic group [10%] and seven in the dyskinetic group [14%]). Results: Results showed an early and late improvement in New York Heart Association functional class and ejection fraction (from 23% ± 5% to 31% ± 11% to 40% ± 13% in akinetic patients and from 23% ± 6% to 41% ± 10% to 41% ± 12% in dyskinetic patients). Ventricular tachycardia was reduced significantly in both groups early and late after the operation. Conclusion: We conclude that in patients with either large akinetic or dyskinetic scar and severe left ventricular dysfunction, endoventricular circular patch plasty associated with coronary grafting and cryotherapy, when indicated, provides surviving patients with significant improvement in cardiac function. This approach can be considered as an alternative to heart transplantation in patients with severe left ventricular dysfunction. (J Thorac Cardiovasc Surg 1998;116:50-9)

Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia.

We have studied the regional cerebral blood flow (rCBF) changes induced by the execution of a finger-to-thumb opposition motor task in the supplementary and primary motor cortex of two groups of parkinsonian patients on L-dopa medication, the first one without L-dopa induced dyskinesia (n = 23) and the other with moderate peak-dose dyskinesia (n = 15), and of a group of 14 normal subjects. Single photon emission tomography with i.v. 133Xe was used to measure the rCBF changes. The dyskinetic parkinsonian patients exhibited a pattern of response which was markedly different from those of the normal subjects and non-dyskinetic parkinsonian patients, with a significant overactivation in the supplementary motor area and the ipsi- and contralateral primary motor areas. These results are compatible with the hypothesis that an hyperkinetic abnormal involuntary movement, like L-dopa-induced peak dose dyskinesia, is due to a disinhibition of the primary and associated motor cortex secondary to an excessive outflow of the pallidothalamocortical motor loop.