Mechanism of cell death in myeloma NS(O) in culture

OBJECT: The goal of this study was to investigate the impact of mild or moderate degrees of degenerative or ischemic encephalopathy on predicting clinical outcome following unilateral posteroventral medial pallidotomy for treatment of advanced Parkinson's disease (PD). METHODS: Thirty-five patients with PD were studied prospectively. The presence and degree of cortical atrophy, ventriculomegaly, deep white matter lesions (DWML), periventricular lucencies (PVL), and the presence of lacunes and status cribriformis (multiple and bilateral enlarged Virchow-Robin spaces) were determined by magnetic resonance (MR) imaging before the patients underwent stereotactic pallidotomy performed according to a standard protocol. Clinical outcome was measured using a standard battery of tests including application of the Unified Parkinson's Disease Rating Scale (UPDRS). The preoperative MR imaging features were correlated with UPDRS subscores such as motor "off' score, the activities of daily living (ADL) off score, the off subscore for bradykinesia, the percentage of "on" time dyskinesias, and a global outcome rating. The MR findings were also correlated with the occurrence of side effects. Global outcome was rated as markedly improved in 22 patients (63%) and as moderately improved in 12 patients (34%) 6 months postoperatively. At the 1-year follow-up examination, global outcome in 31 patients was rated as markedly improved in 14 patients (45%), as moderately improved in another 14 (45%), as slightly improved in two (6%), and as worse in one patient (3%). The mean UPDRS motor off score changed from 58.7 preoperatively to 33.2 at 6 months and 33.4 at 1 year (p < 0.0001), the ADL off score from 31.8 to 18.2 at 6 months and 18.6 at 1 year (p < 0.0001), the off score from contralateral bradykinesia from 11.6 to 5.6 at 6 months and 4.1 at 1 year (p < 0.0001), and the percentage of awake time with dyskinesias from 37.4 to 17.4% at 6 months and 21.1% at 1 year (p < 0.0001). The presence of mild or moderate degrees of cortical atrophy, PVL, and DWML had no effect on clinical outcome. Patients with status cribriformis and those with lacunes tended to show comparatively less improvement in the UPDRS ADL off score (p = 0.014 and p = 0.016, respectively) at 6 months. This tendency was also present in patients with status cribriformis 1 year postoperatively (p = 0.046). Patients with both status cribriformis and lacunes had a higher incidence of transient altered mental status immediately postoperatively (p = 0.05). CONCLUSIONS: Mild-to-moderate degrees of cortical atrophy, ventriculomegaly, and ischemic encephalopathy do not predispose patients to less favorable outcomes following unilateral pallidotomy. Patients with both status cribriformis and lacunes have a higher risk of transient side effects; however, with regard to clinical outcome, these patients should not be denied surgical treatment.     

Posteroventral medial pallidotomy in advanced Parkinson's disease

BACKGROUND: Posteroventral medial pallidotomy sometimes produces striking improvement in patients with advanced Parkinson's disease, but the studies to date have involved small numbers of patients and short-term follow-up. METHODS: Forty patients with Parkinson's disease underwent serial, detailed assessments both after drug withdrawal ("off" period) and while taking their optimal medical regimens ("on" period). All patients were examined preoperatively and 39 were examined at six months; 27 of the patients were also examined at one year, and 11 at two years. RESULTS: The percent improvements at six months were as follows: off-period score for overall motor function, 28 percent (95 percent confidence interval, 19 to 38 percent), with most of the improvement in the contralateral limbs; off-period score for activities of daily living, 29 percent (95 percent confidence interval, 19 to 39 percent); on-period score for contralateral dyskinesias, 82 percent (95 percent confidence interval, 72 to 91 percent); and on-period score for ipsilateral dyskinesias, 44 percent (95 percent confidence interval, 29 to 59 percent). The improvements in dyskinesias and the total scores for off-period parkinsonism, contralateral bradykinesia, and rigidity were sustained in the 11 patients examined at two years. The improvement in ipsilateral dyskinesias was lost after one year, and the improvements in postural stability and gait lasted only three to six months. Approximately half the patients who had been dependent on assistance in activities of daily living in the off period before surgery became independent after surgery. The complications of surgery were generally well tolerated, and there were no significant changes in the use of medication. CONCLUSIONS: In late-stage Parkinson's disease, pallidotomy significantly reduces levodopa-induced dyskinesias and off-period disability. Much of the benefit is sustained at two years, although some improvements, such as those on the ipsilateral side and in axial symptoms, wane within the first year. The on-period symptoms that are resistant to dopaminergic therapy do not respond to pallidotomy.     

Pallidal stimulation: an alternative to pallidotomy?

A resurgence of interest in the surgical treatment of Parkinson's disease (PD) came with the rediscovery of posteroventral pallidotomy by Laitinen in 1985. Laitinen's procedure improved most symptoms in drug-resistant PD, which engendered wide interest in the neurosurgical community. Another lesioning procedure, ventrolateral thalamotomy, has become a powerful alternative to stimulate the nucleus ventralis intermedius, producing high long-term success rates and low morbidity rates. Pallidal stimulation has not met with the same success. According to the literature pallidotomy improves the "on" symptoms of PD, such as dyskinesias, as well as the "off" symptoms, such as rigidity, bradykinesia, and on-off fluctuations. Pallidal stimulation improves bradykinesia and rigidity to a minor extent; however, its strength seems to be in improving levodopa-induced dyskinesias. Stimulation often produces an improvement in the hyper- or dyskinetic upper limbs, but increases the "freezing" phenomenon in the lower limbs at the same time. Considering the small increase in the patient's independence, the high costs of bilateral implants, and the difficulty most patients experience in handling the devices, the question arises as to whether bilateral pallidal stimulation is a real alternative to pallidotomy.     

Outcomes after stereotactically guided pallidotomy for advanced Parkinson's disease

OBJECT: Parkinson's disease (PD) is a prevalent neurodegenerative disorder that becomes refractory to medication as the disease progresses. Although in the past 5 years increasing numbers of patients have undergone stereotactically guided posteroventral pallidotomy for advanced PD, the safety and efficacy of surgery remains to be documented. The goal in this study was to determine the potential operative morbidity and types of functional outcomes by using validated PD rating scales and a patient survey. METHODS: In a prospective analysis of a consecutive surgical series the authors evaluated 58 patients with advanced PD who ranged in age from 40 to 79 years (mean 67 years) and who had undergone surgery between 1994 and 1997. They used a patient survey and the Unified Parkinson's Disease Rating Scale (UPDRS) to study patients during periods of medication administration ("on") and withdrawal ("off"; mean off score before surgery = 96). Temporary surgical morbidity was found in four patients (6.9%), three of whom developed transient dysarthria and one of whom exhibited transient confusion (1.7%). One patient had persistent dysarthria (1.7%). No patient developed a visual field deficit or sustained a brain hemorrhage. All patients were discharged from the hospital within 24 hours. Significant postsurgical improvements were noted in the UPDRS off-period total and motor scores, as well as in tremor, rigidity, bradykinesia, and contralateral dyskinesia (p < 0.005). Improvements persisted in dyskinesia and tremor for the 21 patients who were evaluated past 1 year. The authors found no improvement in any on-period symptoms except dyskinesia. Thirty-one (61 %) of 51 patients surveyed reported functional gains and/or dramatic improvement in symptoms, 17 (33%) reported symptomatic improvement without functional gains, and three (6%) had minimal or no change in symptoms. No change in the mini mental state examination score was noted during follow up. There were no significant postoperative changes in the use of medication. CONCLUSIONS: In advanced PD associated with either a medically refractory state with significant off periods or levodopa-induced dyskinesias, magnetic resonance imaging-guided pallidotomy with macrostimulation was associated with minimal morbidity and yet significantly reduced dyskinesia and off-period disability. These improvements were of value to the patient and persisted beyond the 1st year.     

NMDA but not AMPA receptor antagonists impair the delay-interposed radial maze performance of rats

Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed chronic stimulation of the globus pallidus (CSGP) to duplicate the positive results of pallidotomy with reduced risk of permanent neurologic deficit in patients with advanced PD. The lead for CSGP was stereotactically implanted with the aid of microelectrode recordings in the globus pallidus pars interna. An electrical pulse generator was implanted in the subclavicular region. Stimulation settings were adjusted by computer. Five PD patients (four men, one woman) with disabling symptoms were enrolled. Three of the patients had bilateral implants. At 3 months following the last implant, four patients rated themselves as markedly improved, and one patient was moderately improved. The amount of time in the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p < 0.05). There was a significant improvement in all subscales of the UPDRS (p < 0.05). One patient had an asymptomatic intracranial bleed, one patient had transient hemiparesis during surgery with stimulation, and one patient required surgical repositioning of the lead. Adverse effects caused by stimulation were minimal. CSGP is a safe and effective procedure in PD patients with motor fluctuations and dyskinesias.     

Neurosurgical interventions in the treatment of idiopathic Parkinson disease: neurostimulation and neural implantation

With the exception of thalamotomy for drug-refractory tremor, surgical therapy for Parkinson's disease has been almost abandoned as treatment for Parkinsonian symptoms between 1965 and 1985. Reasons for this development relate to inconsistent postoperative results, complications associated with stereotactic surgical techniques and, most importantly, the advent of levodopa, which is still considered to be the gold standard in pharmacotherapy for Parkinson's disease. However, both, the long-term experience with L-DOPA therapy on the one hand and the progress of advanced stereotactic techniques and fetal graft research on the other hand have lead to reconsideration of surgical therapy in Parkinson's disease for patients, who can not be treated satisfactorily with medication. Both lesions (via thermocoagulation) and/or neurostimulation (via chronic intracerebral implantation of electrodes) in thalamic nuclei (nucleus ventralis oralis posterior/intermedialis thalami; VOP/VIM) may alleviate rest tremor in PD patients. In principle neurostimulation has the significant advantage of reversibility with regard to side effects in comparison to lesion surgery. Furthermore ventro-posterior pallidotomy or chronic stimulation in this structures may ameliorate bradykinesia and levodopa-induced dyskinesias. Additionally, "switching-off" the subthalamic nucleus by neurostimulation has been reported to reduce rigidity, bradykinesia and levodopa-induced ON-OFF-fluctuations. On the other hand, neuronal transplantation of fetal nigral dopamine precursor cells aims at restoring the striatal dopamine deficit. Both animal and clinical experiments have shown that fetal grafts survive intrastriatal transplantation and may ensue moderate to satisfactory improvements, especially in regard to bradykinesia and ON-OFF-fluctuations. Further progress in the field of neuronal transplantation will largely depend on the development of alternative cell resources.     

Surgical interventions in the treatment of Parkinson's disease (PD) and essential tremor (ET): medial pallidotomy in PD and chronic deep brain stimulation (DBS) in PD and ET

Surgical treatments for PD and ET are promising. Medial Pallidotomy, the surgical lesioning of the pallidum, often improves symptoms of long-standing PD. We enrolled twenty-seven late stage PD patients for unilateral medial pallidotomy who were then assessed by the Core Assessment Program for Intracranial Transplantation (CAPIT) protocol. One year after surgery persistent improvement was seen contralateral to the lesion in the following features: drug-induced dyskinesias (92%), akinesia (38%), rigidity (51%), and tremor (42%). Complications included transient dysarthria (7 patients), facial weakness (9 patients), limb weakness (1 patient), swallowing problems (4 patients) and intracerebral haemorrhage (1 patient). Thalamic DBS may improve tremor in PD and ET patients. Therefore, we enrolled fifteen patients (9 PD and 6 ET patients) with disabling tremor, unresponsive to medication. They were assessed by the United Parkinson's Disease Rating Scale (UPDRS) and the Tremor Rating Scale (for PD and ET patients, respectively). Three months after surgery, limb tremor contralateral to stimulation improved by 71% in PD patients and 76% in ET patients. Complications included transient paresthesias (all), confusional state (1 patient) and intracerebral bleed (1 patient). Unilateral medial pallidotomy safely improves some Parkinsonian symptoms contralateral to the lesion. Thalamic DBS may effectively and safely improve contralateral limb tremor in PD and ET.     

Bilateral posteroventral pallidotomy in advanced Parkinson's disease in three patients

In this report, we describe the effect of staged bilateral posteroventral pallidotomy in three patients with advanced Parkinson's disease who were all of the young-onset type. Two patients had developed response fluctuations after the use of levodopa, with severe hypokinesia, painful dystonia, and rigidity in the "off" phase and violent dyskinesias in the "on" phase. One patient, in a continuous hypokinetic rigid state, was totally unresponsive to dopaminergic medication. All were at Hoehn and Yahr stage 5 in the "off" phase before surgery. After surgery, the hypokinetic state was reversed and dyskinesias were abolished in all patients. Hoehn and Yahr stages were 3 in the "off" phase postoperatively. Overall functional improvement was marked and lasting after follow-up for 7, 12, and 13 months, respectively. Complications were visual field deficit and transient central facial paresis, both in the same patient. Bilateral posteroventral pallidotomy can ameliorate response fluctuations, hypokinesia, rigidity, and painful dystonia in advanced Parkinson's disease.     

Opposite motor effects of pallidal stimulation in Parkinson's disease

We studied the effects--on parkinsonian signs, on levodopa-induced dyskinesias, and on levodopa response--of acute experimental high-frequency stimulation of the internal pallidum (GPi) during off-drug and on-drug phases. Thirteen quadripolar electrodes were evaluated in 8 patients with Parkinson's disease (PD). Stimulation of the most ventral contacts, lying at the ventral margin of or just below the GPi, led to pronounced improvement in rigidity and a complete arrest of levodopa-induced dyskinesias. The antiakinetic effect of levodopa was also blocked and the patients became severely akinetic. Stimulation of the most dorsal contacts, lying at the dorsal border of the GPi or inside the external pallidum, usually led to moderate improvement of off-drug akinesia and could also induce dyskinesias in some patients. When using an intermediate contact for chronic stimulation, a good compromise between these opposite effects was usually obtained, mimicking the effect of pallidotomy. We conclude that there are at least two different functional zones within the globus pallidus, at the basis of a different pathophysiology of the cardinal symptoms of PD. The opposite effects may explain the variable results of pallidal surgery reported in the literature and may also largely explain the paradox of PD surgery. A possible anatomical basis for these differential functional effects could be a functional somatotopy within the GPi, with the segregation of the pallidofugal fibers from the outer portion of the GPi, on one hand, forming the ventral ansa lenticularis and from the inner portion of the GPi, on the other hand, forming the dorsal lenticular fasciculus.     

Cell-cycle-dependent nuclear translocation of HSP70 in amphibian embryonic cells

The Unified Parkinson's Disease Rating Scale (UPDRS) is widely used to assess Parkinson's disease (PD) disability but its metric properties have not been extensively studied. We investigated the factor structure and internal consistency of the Motor Examination section of the UPDRS in a sample of 294 consecutive patients with idiopathic PD who were assessed while in the "on" state. There was a high degree of internal consistency. Factor analysis revealed six clinically distinct factors, three bradykinesia measures (axial/gait, right and left), one rigidity measure, and two tremor measures (rest and postural). These factors accounted for 78% of the variance. Total Motor Examination scores and selected factors correlated well with other examiner-determined global ratings of PD disability (Hoehn and Yahr stage and Schwab-England Activities of Daily Living score). These results suggest that the Motor Examination section of the UPDRS provides a useful measure of PD function as well as severity measures of six clinical disability domains.     

Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease

OBJECTIVE: To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD). BACKGROUND: NMDA receptor blockade can ameliorate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recently found to possess NMDA antagonistic properties. METHODS: Eighteen patients with advanced PD participated in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week treatment arm, parkinsonian and dyskinesia scores were obtained during a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interviews. RESULTS: In the 14 patients completing this trial, amantadine reduced dyskinesia severity by 60% (p = 0.001) compared to placebo, without altering the antiparkinsonian effect of levodopa. Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPDRS and patient-kept diaries. CONCLUSIONS: These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications.     

Imaging of delta- and mu-opioid receptors in temporal lobe epilepsy by positron emission tomography

The authors report the postoperative magnetic resonance (MR) imaging findings in 36 patients with advanced Parkinson's disease who underwent unilateral microelectrode-guided posteroventral pallidotomy. The lesions were placed within 1 mm of the ventral border of the globus pallidus internus (GPi) to include pallidothalamic outflow pathways. Sequential MR studies were obtained within 1 to 3 days postoperatively and at 6-month follow-up examination. Thirty-four (94%) of the 36 patients enjoyed sustained moderate or marked improvement of their parkinsonian symptoms 6 months postoperatively. Transient side effects occurred in five patients (14%), but there were no persistent complications. The pallidal radiofrequency lesions were prolate spheroid shaped and were composed of three concentric zones in the early postoperative studies. The mean volume of the middle zone, corresponding to the area of hemorrhagic coagulation necrosis, was 44.4 +/- 17.6 mm3; the mean lesion volume as defined by the outer zone, corresponding to perilesional edema, was 262.2 +/- 111.6 mm3. Additional edema spreading to the internal capsule was noted in 32 of 34 cases and to the optic tract in 11 of 34 cases. In two patients small ischemic infarctions involving the corona radiata were found, and in one a venous infarction was detected. Ischemic infarction resulted in mild transient Broca's aphasia in one patient, but there was no detectable neurological deficit in the other two. The mean volume of late-phase (6 months) lesions was 22 +/- 28.8 mm3. In three patients no lesion was identified despite sustained clinical improvement. The lesion was located in the posteroventral GPi in all cases except in one patient in whom it was confined to the GP externus (GPe). This 49-year-old woman did not experience sustained benefit. The authors found no consistent correlations between lesion size and location and clinical outcome as measured by a global outcome score, the Unified Parkinson's Disease Rating Scale motor, activities of daily living, and bradykinesia "off" scores or rating of dyskinesias. Lesioning of pallidal and subpallidal pathways may contribute to the sustained clinical benefit in this series. Magnetic resonance imaging analysis showed that intraoperative microelectrode recording facilitated accurate placement of the lesion in this critical area.     

A trial of dextromethorphan in parkinsonian patients with motor response complications

The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60-120 mg/day). The 12 remaining patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double-blind, placebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the anti-Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa-associated motor complications.     

Inhibition of levodopa effects by internal pallidal stimulation

We report three patients with bilateral GPi stimulation for stage 4 Parkinson's disease (PD) with severe levodopa-induced dyskinesias (LID). In all three it was possible to completely inhibit LID using high-stimulation parameters. Parallel to complete inhibition of LID, an inhibition of the anti-akinetic effect of levodopa was observed, whereas, at the same time, rigidity was markedly improved. GPi stimulation is adaptable over time, and stimulation parameters have to be programmed according to off- and on-period motor symptoms. The main interest of stimulation is the possibility of finding a compromise between LID alleviation in on-phase without loss of the beneficial motor effects and improvement in parkinsonism in off-phase. In some patients, residual dyskinesias have to be accepted so as not to aggravate on-period motor symptoms by a presumed overinhibition of basal ganglia outflow.     

Evaluation of the Short Parkinson's Evaluation Scale: a new friendly scale for the evaluation of Parkinson's disease in clinical drug trials

The extensive use of the Unified Parkinson's Disease Rating Scale (UPDRS) has revealed low interrater reliability in some items and redundancy in others. In view of these shortcomings, we have structured a new scale that includes a zero-to three-point scale for each item in the evaluation of PD. The mental axis includes memory, thought disorders, and depression. Activities of daily living (ADL) includes eight items: speech, eating, feeding, dressing, hygiene, handwriting, walking, and turning in bed. The motor examination includes eight items: speech, tremor, rest and posture, rigidity, finger tapping, arising from chair, gait, and postural stability. Complications of therapy were also included: dyskinesias, dystonia, motor fluctuations, and freezing episodes, collected by history. In addition, a global scoring for motor fluctuations that should complement the Hoehn and Yahr Scale was incorporated. In this report, we present a statistical analysis of the ADL, motor evaluation, and complications of therapy sections. Concerning the interrater reliability mean, Kendall's W values were >0.9 for most of the items in the Short Parkinson's Evaluation Scale (SPES). Kendall's W <0.8 (motor evaluation) was found for two items of the SPES and nine items of the UPDRS. The mean interrater reliability for both scales across all seven centers (seven Kendall's W for seven centers) (Mann-Whitney test) showed no statistical differences between the scales. Spearman's correlations between items of both scales were significant. Factor analysis of the SPES and UPDRS data revealed a four-factor solution that explained approximately 60% of the data. All participating centers found the SPES easier to apply and quicker to complete, when compared with the UPDRS. The results obtained strongly favor the introduction of SPES for clinical practice.     

Treatment of parkinson's disease with bromocriptine

Bromocriptine in high doses (up to 100 mg per day) was administered to 14 patients with advanced Parkinson's disease whose disorder was progressing despite optimum treatment with levodopa combined with a peripheral dopa decarboxylase inhibitor (carbidopa). In 10, bromocriptine (mean dose, 57 mg) induced a statistically significant (P less than 0.01) improvement in rigidity, tremor, bradykinesia, gait disturbance and total score. In seven patients levodopa with carbidopa was completely replaced by bromocriptine (mean dose, 70 mg), with improvement in four. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance (on-off effect) were decreased whereas orthostatic hypotension and mental changes were increased. Bromocriptine appears to be a major new agent in Parkinson's disease that is especially promising in patients no longer responding to levodopa.     

Neuropsychological and motor functioning after unilateral anatomically guided posterior ventral pallidotomy. Preoperative performance and three-month follow-up

This study presents baseline and 3-month follow-up motor and neuropsychological data for 22 patients with Parkinson's disease (PD) who underwent anatomically guided unilateral posterior ventral pallidotomy (PVP). Postsurgical improvements were seen in psychomotor speed, fine motor accuracy, and dyskinesia, whereas grip strength decreased on the side contralateral to the surgery. No change was detected in overall level of cognitive functioning, nor were changes demonstrated in memory, language, or working memory when the entire sample of patients was evaluated. When the group was divided on the basis of side of surgery, patients with left-sided pallidotomies showed a decline in verbal fluency. Patients and caregivers reported improvement in psychosocial functioning. These initial findings of improved motor performance and largely unaffected cognitive functions are consistent with results obtained with functional PVP and provide support for the use of anatomically guided posterior ventral pallidotomy in the treatment of motor symptoms of PD.     

Evidence that the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in human serum may not be secreted by the pituitary gland

A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study assessed the efficacy and safety of ropinirole, a nonergoline D2-dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn & Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients (mean age, 62.8 years), stratified by concomitant use of selegiline, were randomized to ropinirole (n = 116) or placebo (n = 125). The starting dose of ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8 mg tid). Primary efficacy endpoint was the percentage improvement in Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Ropinirole-treated patients had a significantly greater percentage improvement in UPDRS motor score than patients who received placebo (+24% vs -3%; p < 0.001). Ropinirole was well tolerated and patient withdrawals were infrequent. Most adverse experiences were related to peripheral dopaminergic activity. Ropinirole monotherapy is an effective and well-tolerated therapeutic option for treatment of early Parkinson's disease.     

Influence of osteophytic size on bone mineral density measured by dual X-ray absorptiometry

Eight of the first 15 patients with advanced Parkinson's disease who underwent microelectrode guided posteroventral pallidotomy developed transient abnormal involuntary movements during thermolesion, four of whom also did so during high frequency macrostimulation. Abnormal involuntary movements found before thermolesion were choreic, ballistic, or choreoathetoid in nature, usually persisted less than 60 minutes, and were contralateral to the site of thermolesion in six and bilateral in two of them. The appearance of abnormal involuntary movements during macrostimulation or thermolesion of the internal globus pallidus correlated with better surgical outcome as measured by UPDRS motor items and CAPIT timed test, so that they seem to be of prognostic value.     

Levodopa-induced dyskinesias in Parkinson's disease phenomenology and pathophysiology

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.