Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow-up of patients.

Bilateral subthalamic nucleus stimulation (STN-DBS) is used to improve parkinsonian symptoms and attenuate levodopa-induced motor complications. In some patients, such clinical improvement allows antiparkinsonian medication (ApMed) withdrawal. We show the clinical outcome at the long-term follow-up of patients with advanced Parkinson's disease (PD) in which STN-DBS was used in monotherapy, and compare the clinical results of patients without medication with those obtained in parkinsonian patients in which ApMed were reduced but could not be totally displaced after surgery. We analyzed clinical outcome of ten patients with PD in which all ApMed was withdrawn after bilateral subthalamic stimulation and 16 parkinsonian patients still taking antiparkinsonian medication after surgery. After 1.5 years, STN-DBS monotherapy produced UPDRS motor scores similar to those observed in the on-drug condition before surgery without the inconvenience of motor fluctuations and dyskinesias. No significant differences were seen in most of clinical outcome measures when comparing patients still taking ApMed with patients in STN-DBS monotherapy but a few patients still taking ApMed presented mild dyskinesias and motor fluctuations and patients with STN-DBS monotherapy did not. STN-DBS is useful in the treatment of advanced PD and in some patients it is possible to maintain this therapy alone in the long term. The therapeutic effect of STN-DBS on motor signs can be equipotent to that of levodopa with the additional benefit of avoiding motor fluctuations and dyskinesias.     

Randomized trial of pallidotomy versus medical therapy for Parkinson's disease

Thirty-six patients with Parkinson's disease (PD) were randomized to either medical therapy (N = 18) or unilateral GPi pallidotomy (N = 18). The primary outcome variable was the change in total Unified Parkinson's Disease Rating Scale (UPDRS) score at 6 months. Secondary outcome variables included subscores and individual parkinsonian symptoms as determined from the UPDRS. At the six month follow-up, patients receiving pallidotomy had a statistically significant reduction (32% decrease) in the total UPDRS score compared to those randomized to medical therapy (5% increase). Following surgery, patients' showed improvement in all the cardinal motor signs of PD including tremor, rigidity, bradykinesia, gait and balance. Drug-induced dyskinesias were also markedly improved. Although the greatest improvement occurred on the side contralateral to the lesion, significant ipsilateral improvement was also observed for bradykinesia, rigidity and drug-induced dyskinesias. A total of twenty patients have been followed for 2 years to assess the effect of time on clinical outcome. These patients have shown sustained improvement in the total UPDRS (p < 0.0001), "off" motor (p < 0.0001) and complications of therapy subscores (p < 0.0001). Sustained improvement was also seen for tremor, rigidity, bradykinesia, percent on time and drug-induced dyskinesias.     

Long‐term outcomes of surgical therapies for Parkinson's disease

The surgical lesion of different brain structures has been used as a treatment for Parkinson's disease (PD) for several decades. More recently, the favored therapeutic approach has involved the administration of levodopa and the use of DBS. These two major therapeutic advances have greatly modified both the clinical condition of patients and the history of the disease. With the introduction of L ‐dopa in 1967, patients could regain mobility, because their akinesia, tremor, and rigidity were greatly improved, with consequent significant improvement in quality of life and increased life expectancy. However, after the so‐called “honeymoon” period in which the disease seemed to be controlled, motor fluctuations and L ‐dopa‐induced dyskinesias mitigated the initial enthusiasm. In the 1990s, unilateral pallidotomy and DBS of the globus palllidus internus and STN reduced these motor fluctuations and dyskinesias remarkably, thereby inaugurating a new era in the surgical treatment of PD. Short‐ and medium‐term follow‐up studies of patients who underwent surgery have documented sustained, significant motor benefits. However, given the progressive nature of PD and the purely symptomatic effects of pallidotomy and DBS, the long‐term clinical evolution of these surgical patients currently seems to be associated with a new PD phenotype, mainly characterized by axial motor problems and cognitive impairment. Here, we analyze the long‐term clinical outcomes of surgical PD patients with at least 5‐year follow‐up, focusing on the long‐term motor symptoms that were initially responsive to surgery. © 2012 Movement Disorder Society     

Pallidotomy versus pallidal stimulation

Both posteroventral pallidotomy and pallidal deep brain stimulation (DBS) have a documented effect on Parkinsonian symptoms. DBS is more costly and more laborious than pallidotomy. The aim of this study was to analyse the respective long-term effect of each surgical procedure on contralateral symptoms in the same patients. Five consecutive patients, two women and three men, who at first surgery had a mean age of 64 years and a mean duration of disease of 18 years, received a pallidotomy contralateral to the more symptomatic side of the body. At a mean of 14 months later, the same patients received a pallidal DBS on the side contralateral to the pallidotomy. All patients had on-off phenomena and dyskinesias. There were three left-sided and two right-sided pallidotomies, and, subsequently, two left-sided and three right-sided pallidal DBS. The latest evaluation was performed 37 months (range 22-60) after the pallidotomy and 22 months (range 12-33) after the pallidal DBS. Mean UPDRS motor score pre-operatively was 49 and at last follow-up 33 (32.7% improvement, p<0.05). Appendicular items 20-26 contralateral to pallidotomy remained improved more significantly than contralateral to DBS. Dyskinesia scores were also improved more markedly contralateral to the pallidotomy. Two patients exhibited moderate dysarthria and one patient severe dysphonia following DBS. Symptoms contralateral to the chronologically older pallidotomy, especially dyskinesias, rigidity and tremor, were still more improved than symptoms contralateral to the more recent pallidal DBS, despite numerous post-operative patient visits to optimise stimulation parameters.     

Long term outcome of unilateral pallidotomy: follow up of 15 patients for 3 years

OBJECTIVES: With the advent of new antiparkinsonian drug therapy and promising results from subthalamic and pallidal stimulation, this study evaluated the long term efficacy of unilateral pallidotomy, a technique which has gained popularity over the past decade for the management of advanced Parkinson's disease. METHODS: The 15 patients reported here are part of the original cohort of 24 patients who underwent posteroventral pallidotomy for motor fluctuations and disabling dyskinesias 3 years ago as part of a prospective study. Evaluation scales included the unified Parkinson's disease rating scale, the Goetz dyskinesia scale, and the Purdue pegboard test. RESULTS: When compared with the prepallidotomy scores, the reduction in the limb dyskinesias and off state tremor scores persisted on the side contralateral to pallidotomy at the end of 3 years (dyskinesias were reduced by 64% (p<0.01) and tremor by 63% (p<0.05). Other measures tended to deteriorate. The dosage of antiparkinsonian medications did not change significantly from 3 months prepallidotomy to 3 years postpallidotomy. CONCLUSIONS: Although unilateral pallidotomy is useful in controlling the contralateral dyskinesias and tremor 3 years after surgery, all other early benefits disappear and activities of daily living continue to worsen.     

Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease

CONTEXT: Subthalamic nucleus (STN) stimulation may be effective in ameliorating parkinsonian symptoms even to the extent to permit levodopa withdrawal. OBJECTIVES: To analyze the efficacy of STN stimulation in patients with Parkinson disease (PD) and to determine if levodopa may be withdrawn after surgery. DESIGN: Before-after trial. SETTING: Referral center, hospitalized care. PATIENTS: Fifteen patients with advanced PD. INTERVENTIONS: Microelectrode-guided bilateral STN high-frequency stimulation. OUTCOME MEASURES: Before surgery patients were evaluated in off-medication and on-medication conditions. Dopaminergic drug dosages were reduced after surgery, aiming for complete withdrawal. Six months after surgery, patients were reeavaluated in off- and on-medication conditions, with the stimulation turned on and off. RESULTS: Total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the off-medication condition improved by 65.9%; and axial symptoms, bradykinesia, rigidity, and tremor improved by 65.8%, 60.4%, 66.1%, and 81.1%, respectively. UPDRS part II scores were reduced by 71.8% and Schwab and England scores improved by 45.3%. Levodopa was withdrawn in 8 patients and the overall levodopa dose was reduced 80.4%. "Off" time was reduced 89.7% and the severity of dyskinesias decreased 80.6% after surgery. All results reached significance (P<.001). Stimulation of the STN achieved antiparkinsonian effect similar to that of treatment with levodopa. No life-threatening adverse effects occurred. CONCLUSIONS: Bilateral STN stimulation safely improves all parkinsonian symptoms, decreases or eliminates the need for levodopa, and ameliorates motor fluctuations and dyskinesias. Complete withdrawal of levodopa is feasible with this technique and the overall motor effect of STN stimulation is quantitatively comparable to that obtained with levodopa.     

Thalamic, pallidal, or subthalamic surgery for Parkinson's disease?

Levodopa is a highly effective treatment of all motor symptoms of Parkinson's disease. However, long-term treatment with levodopa can lead to motor fluctuations and levodopa-induced dyskinesias. Motor side effects can become so disabling as to warrant surgical treatment. Both ablative surgery and deep brain stimulation (DBS) for Parkinson's disease (PD) can be performed in different target areas. Thalamic surgery mainly improves tremor, and to a lesser extent also rigidity and dyskinesias, whereas pallidal and subthalamic nucleus surgery improves all motor symptoms and levodopa-induced dyskinesias. The efficacy and safety of unilateral pallidotomy is well established. DBS has a lower morbidity and is safe enough to be performed bilaterally. The subthalamic nucleus (STN) presently seems to be the most promising target for DBS in advanced stage PD.     

Effects of gabapentin on the motor response to levodopa: a double-blind, placebo-controlled, crossover study in patients with complicated Parkinson disease

BACKGROUND: Motor fluctuations and dyskinesias affect many parkinsonian patients chronically treated with levodopa. Imbalance between gabaergic direct and indirect striatopallidal pathways may originate them. Manipulating GABA neurotransmission may be effective in the treatment of these patients. Gabapentin is an antiepileptic drug that increases the synthesis and release of GABA. Previous studies suggest that gabapentin may be useful in Parkinson disease (PD). OBJECTIVE: To know the effects of gabapentin on the motor response to levodopa in PD patients with motor complications. DESIGN: A randomized double-blind, placebo-controlled, cross-over trial with four weeks of treatment. SETTING: A tertiary referral center. PARTICIPANTS: Twenty subjects with PD and motor fluctuations and dyskinesias on stable antiparkinsonian treatment, took gabapentin up to a maximum dose of 2.400 mg/d in three doses and placebo. METHODS: Three levodopa challenges were performed: at the beginning of the study and at the end of each period of treatment (4 weeks). Basal (off) and best (on) motor status were assessed by the UPDRS III. Latency to peak effect, magnitude of motor response (difference between "on" and "off" scores in the UPDRS III), duration of motor response and severity and duration of dyskinesias after each levodopa challenge were assessed. Patients' diaries were administered. RESULTS:: Fifteen patients completed the study. A significant improvement in the basal UPDRS III resulting in a significant reduction in the magnitude of the motor response after gabapentin was obtained (P < 0.001). No other changes were observed, either on pharmacological parameters or in levodopa-induced dyskinesias. Number of daily hours spent in "on," "on with dyskinesias" and "off" also remained unchanged. Tolerance was good, dizziness being the most common side effect. CONCLUSION: Gabapentin improved parkinsonian symptoms (basal UPDRS III and magnitude of the motor response) following levodopa. This improvement was not reflected in the daily motor situation of patients. Dyskinesias remained unchanged. Gabapentin was well tolerated. Further studies are needed to know the impact of these results in the long-term.     

Variance in effects of subthalamic nucleus stimulation]

Chronic stimulation of subthalamus nucleus (STN) is effective in treating severe motor fluctuation and levodopa induced dyskinesia as well as parkinsonian motor symptoms. The improvement of peak-dose/diphasic dyskinesias of STN stimulation is considered to be due to the decrease in the daily dosage of antiparkinsonian drugs. However one report pointed out that STN stimulation improved directly levodopa induced dyskinesia. Moreover the timing of the improvement for levodopa induced dyskinesia is not yet obvious. In the present study, we have assessed variance in the latency of improvement of levodopa induced dyskinesia due to STN stimulation. In addition, we would clarify an issue which cite of STN stimulation improved parkinsonian symptoms and motor complication (motor dyskinesias and motor fluctuation). We have studied seven patients diagnosed with advanced idiopathic Parkinson's disease with motor fluctuations and levodopa induced dyskinesias. Before and after the implantation of stimulating electrode, patients were assessed by the Unified Parkinson's Disease Rating Scale and % 'OFF' motor state. The dosage of the antiparkinsonian medication was not modified for one month prior to implantation. Following implantation, dosage of the medication and strength of stimulation was adjusted, if necessary. Symptoms of motor fluctuation and dyskinesia improved in all patients six month after surgery. The mean off-time duration and dyskinesia disability improved compared with presurgical conditions. However, the time course of the improvement of dyskinesias was not the same among patients. Contralateral limb dyskinesias in three patients improved immediately after the stimulation without modification of medication. In contrast, the stimulation worsened contralateral limb dyskinesias in other three patients immediately following the surgery. In two of the three patients, dyskinesias gradually improved within one month after surgery without reducing the dosage of medication. Dyskinesias of the other patient improved following a reduction in the dosage of medication one month after the surgery. Improvement of parkinsonian symptoms of the patients with longer latency of stimulation effect for dyskinesias was better than that of the patients with shorter latency. Stimulation cite of the former group appeared to locate more central than that of the latter group. Latency and strength of the effects of STN stimulation are variable.     

Unilateral pallidotomy in advanced Parkinson's disease: a retrospective study of 26 patients.

OBJECTIVE: To evaluate the effects of unilateral pallidotomy in patients with Parkinson's disease (PD). PATIENTS AND METHODS: Twenty-six patients with PD and disabling dyskinesias, painful and/or disabling dystonia, and/or pain as part of PD despite optimal pharmacotherapy underwent unilateral pallidotomy. For assessment, the Unified Parkinson's Disease Rating Scale (UPDRS; part II and III), Hoehn and Yahr staging, the Schwab and England scale, a Dyskinesia Rating Scale, and timed tests were used. Assessment was performed in defined "off' and "on," and on average 2 months before and 7.5 months after the unilateral pallidotomy. Adverse effects were classified as transient or permanent and as major or minor. RESULTS: In the "off' phase, the median UPDRS II score improved from 26.5 to 20.5 (23%) and the median UPDRS III score improved from 47.5 to 33.0 (31%). In the "on" phase, dyskinesias contralateral to the side of the procedure improved with 88% ipsilateral dyskinesias improved only temporarily, and the total UPDRS II and III scores remained unchanged. Thirteen patients had transient adverse effects, three patients had permanent, and two patients had a combination of transient and permanent adverse effects. The transient adverse effects in two patients were classified as major. CONCLUSION: Stereotactic unilateral pallidotomy can improve symptoms and disability in the "off' phase. In the "on" phase, dyskinesias disappeared at the side contralateral to the procedure. Permanent minor complications of pallidotomy occurred in 19% of the patients.     

Outcomes following staged bilateral pallidotomy in advanced Parkinson's disease

The authors assessed clinical outcome for up to one year after staged bilateral pallidotomy in 14 patients with advanced PD. One year after surgery, dyskinesias were virtually abolished and there were significant reductions in "off" time (67%) and activities of daily living "off" scores (24%), as well as nonsignificant reduction in "off" motor score (39%); "on" scores were unchanged. One patient developed a visual field deficit; two had transient confusion. Staged bilateral pallidotomy improves motor function in selected patients with advanced PD.     

Long-term efficacy of posteroventral pallidotomy in the treatment of Parkinson's disease

The authors describe results of unilateral posteroventral pallidotomy (PVP) in 89 patients with PD. At 3 months after surgery, 81.9% of the patients reported marked or moderate improvement in their parkinsonian symptoms. Postoperative Unified PD Rating Scale "off" state mean total motor score improved by 35.5% and the mean activities of daily living score by 33.7% (p <0.001). Improvements in parkinsonian symptoms were maintained in both"off" and "on" states in 62 patients at 12 months after PVP and in 41 patients who were followed for 18 months or longer (mean 26.6 months).     

Dopaminergic therapy and subthalamic stimulation in Parkinson’s disease: a review of 5-year reports

The long-term efficacy and safety of deep brain stimulation (DBS) implant for Parkinson’s disease (PD) is described in several recent papers. This procedure has been reported to permit a stable reduction of dopaminergic therapy requirements for up to 5 years, although some expectation of deterioration in non-dopaminergic signs has been recently stated. Our aim is to perform a literature-based review of papers available describing long-term post-operative follow-up after a bilateral implant for subthalamic DBS (STN-DBS). Only peer-reviewed published papers with a post-operative follow-up of at least 5 years were considered. Clinical outcome, disease progression and side effects were assessed at baseline and 2 (or 3 years) and 5 years after surgery. Seven papers were included in the review. A total of 238 patients were analyzed. STN-DBS was confirmed to be an effective treatment for selected patients with PD. In all studies, off-related motor symptoms improved dramatically, compared with pre-implant, at 2 (or 3, according to the study) years and this result persisted at 5-year evaluations. Antiparkinsonian drug reductions, improvements in motor fluctuations and dyskinesias, functional measures and the progression of underlying PD were also reported in all series. Some axial scores, in particular postural stability and speech, improved transiently. Persisting adverse effects included eyelid opening apraxia, weight gain, psychiatric disorders, depression, dysarthria, dyskinesias, and apathy. The present review of the 5-year observations confirms that STN-DBS is a powerful method in the management of PD, but its long-term effects must be thoroughly assessed.

     

Treatment of advanced Parkinson's disease by posterior GPi pallidotomy: 1-year results of a pilot study

The effects of posterior internal pallidal ablation (GPi pallidotomy) on parkinsonian signs and symptoms were studied in 15 patients with medically intracally intractable Parkinson's disease(PD). The sensorimotor territory of the internal portion of the globus pallidus and the adjacent optic tract and internal capsule were identified with microelectrode recording and stimulation. Radiofrequency lesions were then created in the identified sensorimotor territory. Pallidotomy significantly improved all cardinal parkinsonian motor signs (tremor, rigidity, akinesia/bradykinesia, and gait dysfunction) and reduced drug-induced motor fluctuations and dyskinesias. The improvements occurred predominately contralateral to the lesion, but were also present ipsilaterally. Early postoperative (3-month), mean total United Parkinson's Disease Rating Scale scores improved by 30.1% from preoperative values. Mean combined “on/off” Schwab and England Scale scores, a measure of functional independence, increased from 48.8% to 73.0% postoperatively. The mean total United Parkinson's Disease Rating Scale and Schwab and England scores did not show a statistically significant decline over the 1-year postoperative period. Surgery resulted in little morbidity, including a lack of significant deficits on neuropsychological and psychiatric testing. Physical and social functioning and vitality measures on the Medical Outcome Scale also showed significant improvement over the postoperative period. The findings of this pilot study demonstrate that ablation of the sensorimotor portion of the internal pallidum is a highly effective treatment for advanced PD, with benefits sustained at 1 year.     

Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease

BACKGROUND: Motor fluctuations and dyskinesias can cause disability and reduce quality of life for patients with Parkinson disease (PD). OBJECTIVES: To evaluate factors associated with the development of motor fluctuations and dyskinesias and to assess the sequence in which they occur in individual patients. DESIGN: We performed a retrospective analysis of data from a randomized clinical trial comparing pramipexole dihydrochloride and levodopa as initial treatment for PD. Subjects were followed up for 48 to 58 months and evaluated at 3-month intervals for the presence of motor fluctuations and dyskinesias. SETTING: Academic and private practices. Patients Three hundred one patients with early Parkinson disease were enrolled in this study between October 2, 1996, and August 21, 1997, and were observed through August 24, 2001, when the last patient enrolled completed 4 years of follow-up. MAIN OUTCOME MEASURES: Order of appearance of motor fluctuations and dyskinesias, time to the first occurrence of motor fluctuations, and time to the first occurrence of dyskinesias. RESULTS: One hundred eighty-nine subjects (62.8%) developed motor complications. Of these, 71 (37.6%) developed fluctuations but not dyskinesias, 23 (12.2%) developed dyskinesias but not fluctuations, 48 (25.4%) developed fluctuations before dyskinesias, 33 (17.5%) developed dyskinesias before fluctuations, and 14 (7.4%) developed both at the same time. Factors significantly associated with earlier occurrence of dyskinesia were Hoehn and Yahr stage of 2 or higher, cumulative levodopa dose, cumulative levodopa equivalent dose (levodopa plus pramipexole), and occurrence of motor fluctuations. Pramipexole treatment was associated with later occurrence of dyskinesias. Factors associated with earlier occurrence of motor fluctuations were cumulative levodopa dose, cumulative levodopa equivalent dose, and occurrence of dyskinesias. Factors associated with later occurrence of motor fluctuations were age at onset of 65 years or older and pramipexole treatment. CONCLUSIONS: Higher cumulative levodopa doses and higher cumulative levodopa equivalent doses (levodopa plus pramipexole) were associated with the earlier occurrence of motor complications. Motor fluctuations and dyskinesias appear to be interrelated because the presence of one is associated with the earlier development of the other.     

Stimulation of the subthalamic nucleus in a patient with Parkinson disease and essential tremor

BACKGROUND: The preferred surgical target for the treatment of Parkinson disease (PD) is either the internal globus pallidus or the subthalamic nucleus (STN); the target for treatment of essential tremor (ET) is the thalamic subnucleus ventralis intermedius (Vim). Some patients with PD have coexistent ET, and the identification of a single surgical target to treat both parkinsonian motor symptoms and ET would be of practical importance. OBJECTIVE: To describe the use of the STN target in deep brain stimulator (DBS) surgery to treat PD motor symptoms and the action-postural tremor of ET. DESIGN: Case report. PATIENT: A 62-year-old man had a greater than 30-year history of action-postural tremor in both hands, well controlled with beta-blockers for more than 20 years. He developed resting tremor, bradykinesia, and rigidity on his right side that progressed to his left side during the past 10 years. Dopaminergic medication improved his rigidity and bradykinesia, with only mild improvement of his resting tremor and no effect on his action-postural tremor. INTERVENTIONS: Left pallidotomy followed by placement of a left DBS in the Vim and subsequent placement of a right STN DBS. MAIN OUTCOME MEASURES: Control of symptoms of PD and ET. RESULTS: The left pallidotomy controlled the patient's parkinsonian motor symptoms on the right side of his body, but did not affect the action-postural component of his tremor. The symptoms on the left side of the body, including both an action-postural and a resting tremor (as well as the rigidity and bradykinesia), improved after placement of a single right STN DBS. CONCLUSION: Placement of an STN DBS should be considered as the procedure of choice for surgical treatment of patients with a combination of PD and ET.     

Pallidal stimulation in advanced Parkinson's patients with contraindications for subthalamic stimulation

The aim of this study was to evaluate the efficacy and safety of bilateral pallidal (GPi) deep brain stimulation (DBS) 6 months after surgery in advanced parkinsonian patients whose dopa‐resistant axial motor signs or cognitive decline constituted contraindications for subthalamic nucleus (STN) DBS. Seventeen patients with a mean age of 59.3 ± 7.1 years (range, 45–70), mean disease duration of 12.5 ± 4.3 years (range, 7–20), and contraindications for STN DBS, underwent bilateral GPi DBS. They were evaluated before surgery and 6 months afterward, in accordance with Core Assessment Program for Intracerebral Transplantation recommendations. There were mean improvements of 41.1% in the UPDRS III motor score in the off‐dopa condition and 20.3% in the activities of daily living score. Motor fluctuations were reduced by 22.9% and dyskinesias by 68.6%. Axial motor signs improved in the off‐dopa condition by 34.2%. Neuropsychological performances remained unchanged at the 6‐month assessment. Bilateral GPi DBS is both safe and effective in advanced parkinsonian patients with untreatable motor fluctuations, for whom STN DBS is contraindicated due to dopa‐resistant axial motor signs or cognitive decline. As such, it should be regarded as a viable option for these patients. © 2010 Movement Disorder Society     

Bilateral pallidotomy in Parkinson's disease: a retrospective study.

We evaluated the effects of bilateral pallidotomy in patients with advanced Parkinson's disease. Thirteen patients with Parkinson's disease had a staged bilateral pallidotomy if they had severe response fluctuations, dyskinesias, painful dystonia, or bradykinesia despite optimum pharmacological treatment. Assessment scales were the Unified Parkinson's Disease Rating scale (UPDRS), the Schwab and England scale, and a questionnaire on the effects of disability in activities of daily living and adverse effects. Postoperative magnetic resonance imaging was evaluated for lesion location and extension. The median off-phase UPDRS motor score was reduced from 43.5 to 29 after the first pallidotomy, and it was further reduced to 23.5 after the second pallidotomy (n = 8). The UPDRS activities of daily living off-phase score improved from 28.5 to 20.5 after the first pallidotomy and to 19 after the second pallidotomy (n = 6). The Schwab and England scale off-phase score showed an improvement after both procedures, first from 40 to 60, and thereafter to 90 (n = 8). On-phase dyskinesias were reduced substantially. Eight patients had adverse effects, of whom five had problems with speech. One patient became hemiplegic due to a delayed infarction. Ten patients experienced further benefit from the second procedure. Bilateral pallidotomy reduces dyskinesias. A second contralateral pallidotomy may reduce parkinsonism, although to a lesser degree compared with the first pallidotomy and with an increased risk for adverse effects.     

Subcutaneous continuous apomorphine infusion in fluctuating patients with Parkinson's disease: long-term results

Fluctuations in motor disability and dyskinesias are the major problem in the long-term treatment of Parkinson's disease (PD). Many authors and ourselves have shown that by giving patients a continuous infusion of levodopa it is possible to control motor fluctuations. Levodopa can be administered continuously only be intravenous, intragastric or intrajejunal delivery. Continuous dopaminergic stimulation an be achieved more easily by infusing dopamine agonists subcutaneously. Apomorphine is a potent water-soluble dopamine receptor agonist that has been shown to successfully control motor fluctuation when subcutaneously infused in complicated parkinsonian patients. We report the clinical data of 30 PD patients having at least five years of treatment with subcutaneous continuous apomorphine infusion.     

Long-term duodenal levodopa infusion in Parkinson’s disease: a 3-year motor and cognitive follow-up study

Duodenal infusion of levodopa/carbidopa gel (Duodopa) is an effective treatment option for advanced Parkinson’s disease (PD). Long-term clinical experience up to 16 years suggests that the safety of this procedure is acceptable, while several observational studies showed that Duodopa reduces motor fluctuations and dyskinesias improving patients’ quality of life (QoL). The aim of this study is to investigate the long-term motor and cognitive outcome of Duodopa treatment in advanced PD patients and its’ impact on the QoL. Twenty-five consecutive PD patients were assessed using the Unified PD rating scale (UPDRS), a battery of neuropsychological tests, and the PD questionnaire (PDQ-39) at baseline and after a mean period of three years of Duodopa treatment. Seventeen out of 25 patients reached the follow-up evaluation; five patients discontinued Duodopa and three patients died of causes unrelated to drug infusion. Duodopa improved motor complications (UPDRS-IV) and quality of life (PDQ-39). A sub-group of subjects (41 %) developed a significant deterioration of cognitive functions over time. The most common adverse events were dislocation and the kinking of the intestinal tube. In conclusion, Duodopa therapy is effective in the long-term treatment of advanced PD patients. Continuous enteral levodopa infusion achieves a reduction of motor fluctuations and dyskinesias improving patients’ QoL, despite the progression of PD motor symptoms and a significant decline in cognitive functions in a sub-group of patients.