Fluctuating parkinsonism: a pilot study of single afternoon dose of levodopa methyl ester

Thirty-four patients with idiopathic fluctuating Parkinson's disease and early afternoon delayed on or severely resistant off periods, in spite of long-term antiparkinsonian therapy, were studied. The first afternoon levodopa administration was substituted with an equimolar dosage of the liquid formulation levodopa methyl ester (LDME). The major end-points for efficacy were latency to on and duration of on periods. The patients were divided into five subgroups according to their baseline treatment and they were evaluated monthly for 6 months using the Unified Parkinson's Disease Rating Scale. The patients completed weekly self-evaluation using an on-off chart. LDME was well tolerated by all the patients. A statistically significant reduction in latency to on was observed in all patients. The clinical effect of LDME remained stable during the treatment period (repeat measures ANOVA). The more rapid clinical effect of LDME and its stable and predictable antiparkinsonian activity represents a new and useful approach for treating patients with complicated Parkinson's disease.     

Double-blind study of the activity and tolerability of cabergoline versus placebo in parkinsonians with motor fluctuations

The use of a dopamine agonist with a long duration of action has theoretical advantages in attempting to reduce the motor fluctuations in Parkinson's disease. We report the results of a double-blind controlled study of adding cabergoline, an ergot derivative with potent long-lasting high affinity for the D2 receptor, to levodopa therapy in 37 patients with severe fluctuations in response to treatment. Increasing dosages of cabergoline (19 patients) or placebo (18 patients) were added to each patient's stable levodopa regime. The two patient groups were similar at baseline in terms of age, disease duration, duration of levodopa treatment, and average hours off per day. Following incremental dose titration, patients in the cabergoline group had a significant reduction in hours off per day from 5.0 (SD 2.1) to 3.0 (SD 2.5), but there was no change in this measure in the placebo group [4.0 (2.2) and 3.3 (2.3) respectively]. This was not at the expense of a significant increase in dyskinesia. However, there was no difference between the groups when comparing their average Hoehn and Yahr stage of disease, and Schwab and England activities of daily living index.     

International (NL-UK) double-blind study of Sinemet CR and standard Sinemet (25/100) in 170 patients with fluctuating Parkinson's disease

One hundred and seventy patients with fluctuating Parkinson's disease participated in an international clinical trial to compare the effects of controlled-released Sinemet 50/200 (mg carbidopa/mg levodopa; Sinemet CR) with standard Sinemet 25/100 (Sinemet STD). The study design involved an 8-week open-label titration (dose-finding) phase (STD and CR preparations given individually during weeks 1–4 and 5–8 respectively) followed by a 24-week double-blind, double-dummy (placebo) treatment period. Drug efficacy was assessed using: (a) data from patients' diaries (i.e. on-off periods) (b) the functional disability profile (Northwestern University Disability Scale), (c) the neurological signs and symptoms (New York University Parkinson's Disease Scale, NYUPDS), (d) global evaluations made by the patient and treating physician and (e) the patient's evaluation of sleep. The results indicate that the number of off periods and the total NYUPDS score decreased significantly in the patients treated with Sinemet CR compared with those treated with Sinemet STD. Furthermore, the patient's global evaluation was significantly better in the Sinemet CR group. The number of drug-related adverse experiences was similar in the two groups, and only one serious event of this nature was reported.     

Kinematic properties of slow arm movements in Parkinson's disease

Present pathophysiological concepts of bradykinesia stress an impairment of fast movements in Parkinson's disease. It is, however, unknown whether bradykinetic movements are different from slow movements of normal subjects. We recorded trajectories of unrestrained natural arm movements from normal subjects and patients with Parkinson's disease. The experiment required the execution of pointing movements for different movement distances and velocities. The shape of trajectories was found to be changed in Parkinson's disease. The steepness of the initial segment and the relation between steepness of the initial segment and final segment both exceeded corresponding values in normal subjects. An analysis of velocity profiles showed an impaired synchrony of vertical and horizontal velocity components. The difference from normal subjects increased with movement velocity. Parkinsonian patients suffered from a fundamental defect in the composition of complex sequences of motor programs required to perform natural arm movements.     

An open-label evaluation of the tolerability and safety of Stalevo® (carbidopa, levodopa and entacapone) in Parkinson’s disease patients experiencing wearing-off

Summary. Objectives: To evaluate the tolerability, safety and efficacy of Stalevo® (carbidopa, levodopa and entacapone) in Parkinsons disease (PD). Background: Levodopa provides the most effective symptom control for the treatment of Parkinsons disease (PD). However, its long-term use is limited by the development of motor complications such as wearing-off. Catechol-O-methyltransferase (COMT) inhibitors such as entacapone extend the plasma half-life of levodopa and reduce off time. Stalevo is a new levodopa product that combines carbidopa, levodopa and entacapone in one tablet. Clinical studies have not been reported with this compound. Design methods: An open-label, multi-center US trial evaluated 169 consecutive PD patients experiencing end-of-dose wearing-off, with (n=39) and without (n=130) mild dyskinesia. Patients were switched from immediate-release carbidopa/levodopa to Stalevo and were treated for four weeks. Assessments included tolerability measures, adverse events profile, the disease-specific quality of life instrument PDQ-39, UPDRS parts II, III, and question 39 and investigator and patient global clinical assessments. Results: 14 subjects (8%) discontinued treatment with Stalevo, of which 12 (7%) were due to adverse events. 11/130 (8.5%) subjects developed new onset dyskinesia and 17/39 (43.6%) of patients with existing dyskinesia reported a worsening in their dyskinesia. However, this was managed by a change in dose in 21.4% of patients and in another 10.7% dyskinesias resolved without any need for dose adjustment. Other side effects were infrequent and mild, the most common being nausea (12.4%) dizziness (6.5%) and somnolence (6.5%). Stalevo treatment resulted in significant improvements in PDQ-39 and UPDRS (II+III) scores (p<0.001). Assessment of off time demonstrated a reduction in off time in 32% of patients, compared with an increase in 7% of patients. Improvements were noted by both investigator (68.1%) and patient (68.6%) assessments. Conclusions: Switching PD patients experiencing wearing-off from carbidopa/levodopa therapy to Stalevo was safe, well tolerated and resulted in clinical improvement.     

Recent observations on the clinical pharmacology of (-)deprenyl

Summary Serial tyramine challenges were given to 4 patients with Parkinson's disease who had taken 10 mg of a selective monoamine oxidase B inhibitor, (-)deprenyl, for up to eighteen months. In doses sufficient for complete inhibition of the platelet enzyme, no clinically significant adverse pressor reactions (cheese effects) occurred nor were any significant tyramine responses seen when higher doses of deprenyl (40–60 mg daily) were given for three weeks.A balanced crossover study in six healthy young male adults showed that (-)deprenyl was associated with a significant increase in the frequency of periods of wakefulness and stage 2 sleep and a significant decrease in REM sleep and sleep stages 3 and 4.In 85 patients with Parkinson's disease taking 10 mg of (–) deprenyl daily with levodopa and carbidopa for up to eighteen months, a mean dosage reduction of 200 mg levodopa daily was possible; 19 of the 39 patients who had end-of-dose akinesia responded favourably and only one of the 10 patients with on-off oscillations improved. On 10 mg (-)deprenyl daily only 4 patients showed an amphetamine response, but this was more frequent when 40 mg deprenyl was given daily. In 5 patients taking 40 mg (-)deprenyl daily without other medications a mild antiparkinsonian response occurred comparable to that seen with amphetamine.     

Chronic levodopa therapy enhances dopa absorption: Contribution to wearing-off

Summary Effects of the chronic administration of levodopa on its peripheral pharmacokinetics and the contribution of the pharmacokinetics to the pathogenesis of the wearing-off phenomenon are re-evaluated. The concentration of plasma levodopa and clinical symptoms were determined 4 hours after oral levodopa (levodopa 100 mg+benserazide 25 mg) administration on 55 parkinsonian patients. Long-term levodopa therapy markedly increased the peak levodopa concentration (Cmax) and the area under the time-concentration curve (AUC); whereas, it decreased time to the peak concentration (Tmax) and the elimination half-life (T1/2). These results suggest that longterm levodopa therapy accelerates the absorption of levodopa. The wearingoff group (n=23), however, had a markedly higher Cmax and AUC, and a shorter Tmax and T1/2 than the stable group (n=32). We speculate that the clinical expression of stable or wearing-off depends on the absorption of levodopa as well as the presynaptic terminal and post synaptic receptors.     

Adjuvant treatment of parkinson's disease with dopamine agonists: Open trial with bromocriptine and CU 32-085

Summary Bromocriptine (CB-154) and the 8--ergoline CU 32-085, two dopamine receptor agonists, were administered at different times to two series of 22 patients with Parkinson's disease, most of whom took levodopa (plus benserazide) at optimum dosage. The addition of bromocriptine (mean daily dose 32 mg; after 6 months 40 mg) led to a 38.5% reduction of levodopa, while CU 32-085 (mean daily dose 15.2 mg; after 6 months 17.5 mg) permitted a 33.7% reduction in levodopa. The mean dose in two patients on CU 32-085 monotherapy was 55 mg/day. A total of 15 patients tolerated adequate doses of bromocriptine (5–75 mg/day, mean duration of treatment 7.5 months) and 15 patients long-term treatment up to 14 months with CU 32-085 (dose range 1–60 mg/day; mean duration 8.8 months). Both groups showed a significant improvement of total disability score at 6 months by 56% and 67%, respectively, and after 6 months by 69% and 69.4%, respectively, with a significant decrease of all types of disability. All patients with fluctuations and on-off effects rapidly improved on both compounds. Bromocriptine and CU 32-085 were discontinued in seven patients each (32%) because of adverse effects including mental changes (four with bromocriptine, two with CU 32-085), nausea and vomiting (one and two, respectively), hypotension (one each) and increased tremor plus vomiting (one with CU 32-085). Although adverse effects were similar to those observed with levodopa, CU 32-085 in general showed less severe dyskinesia and mental changes but more frequent nausea than bromocriptine and levodopa. While the results of treatment with bromocriptine and CU 32-085 were comparable, the antitremor effect of the latter drug developed more rapidly, even at low dosage. Both compounds were useful in the management of patients with advanced Parkinson's disease, CU 32-085 having a stronger effect on tremor, bradykinesia, fluctuations and on-off effects than bromocriptine.

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Zusammenfassung Bromocriptin (CB-154) und 8--Ergolin (CU 32-085), zwei Dopamin-Rezeptoragonisten, wurden zu verschiedenen Zeitpunkten zwei Gruppen von je 22 Patienten mit M. Parkinson verabreicht, von denen die meisten unter optimal dosierter l-Dopa (mit Benserazid)-Behandlung standen. Die Zugabe von Bromocriptin (mittlere Tagesdosis 32 mg; nach 6 Monaten 40 mg) führte zu einer l-Dopa-Dosisreduktion um 38,5%, während CU 32-085 (mittlere Tagesdosis 15,2 mg; nach 6 Monaten 17,5 mg) eine 33,7%-Dosisreduzierung von l-Dopa gestattete. Die mittlere Tagesdosis bei zwei Patienten mit CU 32-085-Monotherapie betrug 55 mg/Tag. Je 15 Patienten tolerierten adäquate Dosen von Bromocriptin (5–75 mg; mittlere Behandlungsdauer 7,5 Monate) und eine Langzeitbehandlung mit CU 32-085 bis zu 14 Monaten (Dosisbreite 1–60 mg; mittlere Behandlungsdauer 8,8 Monate). Beide Gruppen zeigten signifikante Besserung des total disability score nach 6 Monaten um 56 bzw. 67% und im späteren Verlauf um 69 bzw. 69,4% mit signifikanter Abnahme sämtlicher Behinderungen. Alle Patienten mit Fluktuationen und echten On-Off-Effekten zeigten auf beide Substanzen rasche Besserung. Bromocriptin und CU 32-085 mußten bei je 7 Patienten (32%) wegen schwerer Nebenwirkungen einschließlich psychischer Symptome (4 mit Bromocriptin und 2 mit CU 32-085), Nausea und Brechreiz (1 bzw. 2 Patienten), Hypotension (je 1 Patient) und Zunahme des Tremors mit Brechreiz (1 Patient unter CU 32-085) abgesetzt werden. Obgleich die Nebenwirkungen ähnlich jenen von Levodopa waren, bot CU 32-085 im allgemeinen weniger schwere Dyskinesien und psychische Veränderungen, jedoch häufiger Nausea als Bromocriptin und l-Dopa. Während die Behandlungsresultate von Bromocriptin und CU 32-085 grundsätzlich vergleichbar sind, zeigt die letztere Substanz einen rascher einsetzenden Antitremor-Effekt auch bei niedriger Dosierung. Beide Substanzen sind in der Behandlung von Patienten mit fortgeschrittenem Parkinson-Syndrom günstig, wobei CU 32-085 eine stärkeren Effekt auf Tremor, Bradykinese, Fluktuationen und On-Off-Effekte als Bromocriptin aufweist.

     

Simultaneously evoked primary and cognitive visual evoked potentials distinguish younger and older patients with Parkinson's disease

Summary While it is known that both primary visual processes and visuocognitive responses are affected in Parkinson's Disease (PD), their relationship is not known. It is known that both of these measures can be affected by age per se. Our aims were to determine if in non-demented PD patients visual cognitive event-related potential (ERP) changes simply reflect abnormal primary visual processing and to determine the effects of age and disease on their relationship. In order to do so, we introduce a new normalizing procedure for visual ERPs. In addition to the latencies and amplitudes of P100, N140, P200, N200 and P300 components, the P300-P100 latency difference (termed central processing time —CPT) were measured. In order to avoid confounding factors of absolute amplitude differences due to say, generally low voltage recordings or poor primary visual responses, P300 responses normalized to P100 responses were also evaluated (P300/P100 amplitude ratio). Visual ERPs were obtained in an oddball paradigm in 20 non-demented patients with PD and 20 normal age-matched subjects. The stimuli were horizontal sinusoidal gratings differing only in spatial frequency (0.5 and 1 cycle/degree). While simple ERP latency criteria did not distinguish non-demented PD patients as a group from controls, when younger PD patients were compared to older PD patients and controls CPT acceleratedly increased in younger PD patients. The amplitudes of both N200 and P300 provided significant distinction between patient and control groups. The surprising result emerging from this study is that an individually normalized P300 amplitude provides significant distinction of younger PD patients from age matched normals.     

Quantification of motor deficit in Parkinson's disease with a motor performance test series

Summary It was the purpose of the present study to quantify the expected motor deficit in parkinsonian patients with the computer assisted Motor Performance Test Series (MPS), version 05.87 by Schuhfried (1987) and to examine which of the motor test variables found correlate at a significance level of p<0.01 with items of motor examination recorded at neurological examination and activities of daily living of the Unified Parkinson's Disease Rating Scale (UPDRS), version 3.0.38 patients with idiopathic Parkinson's disease (PD) stages I–IV according to Hoehn and Yahr, aged 41 to 73 years were studied. The study design, i.e. initial rating by the physician followed immediately by testing of motor function with MPS was strictly adhered to in each patient.Physician's rating of rigor and the scores of the semiquantitative tests (finger taps, hand movements and alternating movements) as expression of hypokinesia and the activities of daily living correlated with the 3 factors of the Motor Performance Test Series at a highly significant level independent of disease stage. Tremor is only partly and never significantly reflected in the motor data measured. Stages I–II and II–IV (Hoehn and Yahr) differ significantly in the representative data of the Motor Performance Test Series.The results of the study support the assumption that MPS is a valid instrument for quantitative measurement of the motor deficit in parkinsonian patients, but that only some subtests are pathognomonic.     

Early institution of bromocriptine in Parkinson's disease inhibits the emergence of levodopa-associated motor side effects. Long-term results of the PRADO study

Summary Long-term levodopa treatment in Parkinson's disease is typically associated with motor side effects consisting in dyskinesias and/or fluctuations in motility referred to as the on-off phenomena. The main objective of this prospective, randomized, multi-centre study was to determine to what extent the development of such complications could be prevented by partial substitution of levodopa monotherapy (L-DOPA/benserazide) by bromocriptine in patients with early symptoms of the disease. The basic trial population included 674 newly diagnosed Parkinsonian patients that were randomly allocated to monotherapy with levodopa or a combination therapy based upon a nearly 40% replacement of levodopa by bromocriptine. The two target regimens had to be consistently maintained for 42 months. Parkinsonian symptoms were assessed by means of the Webster rating scale, the Hoehn and Yahr scale, and the Zung Self-Rating Depression scale. Motor side effects and adverse events were recorded at each regular clinic visit.Neurological symptoms improved and stabilized in a similar manner during treatment with both regimens throughout the study period. Motor side effects were observed in more patients on levodopa alone than on combination therapy (28.8 vs 20%; p=0.008). According to Kaplan-Meier estimates the cumulative probability of experiencing motor side effects was 0.43 on monotherapy, compared to 0.28 on combination therapy, which was equal to a one third reduction of risk (p=0.025). In regard to motor side effects, the degree of substitution of levodopa proved relevant: patients with >50% substitution by bromocriptine exhibited half the risk observed in those with <30% (p=0.045). The overall burden of motor side effects, as reflected by a sum score based upon the relevance, the severity and the extent of motor dysfunction, was also significantly less on combination therapy (p=0.046).In conclusion, partial substitution of levodopa by bromocriptine (>30%) as first-line treatment of Parkinson's disease proves active in the prophylaxis of levodopa associated motor side effects. Early combination therapy therefore extends the period of optimal disease control.Dedicated to Dr. H. Bühlmann on the occasion of his 80th birthday     

Entacapone improves the pharmacokinetic and therapeutic response of controlled release levodopa/carbidopa in Parkinson’s patients

Summary. The aim of this trial was to evaluate the effects of the COMT inhibitor entacapone on both the pharmacokinetic profile and clinical efficacy of controlled release levodopa in Parkinsons disease (PD) patients. Twelve PD patients experiencing end-of-dose type motor fluctuations were evaluated in this single-blind, randomized cross-over study. A single dose of either entacapone (200mg) or placebo was co-administered with controlled release levodopa. Blood samples were taken every 30 minutes for 3 hours, and in 6 patients, sampling was continued for a further 3 hours. The clinical response to treatment was evaluated using the Unified Parkinsons Disease Rating Scale motor score. Addition of entacapone to levodopa treatment prolonged the on phase of the PD patients by 37% (p<0.05). This increased duration of on time was concomitant with a significant increase in levodopa bioavailability (AUC). These data confirm the ability of entacapone to enhance the clinical efficacy of controlled release levodopa formulations, and provide further evidence that entacapone is of value in extending the benefits of levodopa in PD patients experiencing motor fluctuations.     

Results of long-term treatment with controlled-release levodopa/carbidopa (Sinemet CR)

Summary 35 Parkinson's disease patients with motor response fluctuations (RF) participated in controlled clinical trials comparing Sinemet CR to Standard Sinemet (STD) at our institutions. 13 of 25 eligible patients continued to two years (the longest possible follow-up from the second study), and 5 of 11 have continued taking CR up to 4 years. At the end of both two and four years, patients were taking significantly fewer medication doses, with a significantly longer interdose interval, and up to two years, experienced fewer off periods than when on Standard Sinemet (STD) alone. Most patients required STD at at least one dose each day to hasten to onset of antiparkinson effect. Sinemet CR is a useful adjunct in the long-term management of motor response fluctuations in Parkinson's disease.     

Gait quantitation in Parkinson's disease — locomotor disability and correlation to clinical rating scales

Summary Stride parameters were established in 17 patients with idiopathic Parkinson's disease (PD; mean age 68.8 yrs.; Hoehn-Yahr stages 2 and 3) and in 33 healthy age-matched controls. Free-walking speed was lower in PD as were stride length and cadence. Impaired locomotor synergies in PD were reflected by a higher coefficient of variation of stride length; step width and its coefficient of variation (the latter related to postural imbalance in locomotion) were not changed. No stride parameter correlated with any total score of either the Hoehn-Yahr Scale, the Unified Parkinson's Disease Rating Scale Motor Examination (UPDRS-III), the Columbia Rating Scale (CURS) or the Webster Rating Scale. Stride length correlated with a CURS-Bradykinesia-Score, whereas gait velocity correlated with UPDRS-III-Axial-Motor-Score and with the CURS-Bradykinesia-Score. Hypokinesia of gait in moderately disabled PD patients is best assessed by combined analysis of stride parameters and locomotion-related subscores from conventional rating scales.     

Juvenile Parkinson's disease with widespread Lewy bodies in the brain

Summary A clinico-pathological case report on a case of juvenile Parkinson's disease (JPD) with widespread Lewy bodies (LBs) in the brain is presented with comparative morphological studies on two demented cases of classical Parkinson's disease (CPD) with disease onset at an older age. The clinical and histological pictures of this JPD case were typical of Parkinson's disease, excepting numerous Lewy bodies in the cerebrum. There were no neurofibrillary change nor senile plaques throughout the CNS. The distribution and histochemical and ultrastructural characters of the histological lesions (i.e., LBs) in the JPD and the two CPD cases were investigated and compared. The comparison showed no qualitative but only quantitative differences between the two types of Parkinson's disease. The present study also revealed that in CPD cases significant numbers of LBs could be present in the cerebral cortex, amygdaloid and claustrum. These lesions can be in part responsible for dementia in CPD.     

Dopaminergic treatment is associated with decreased body weight in patients with Parkinson's disease and dyskinesias

Background and purpose:  Several studies suggested that patients with advanced Parkinson's disease (PD) showed a too low body weight when compared with age-matched, healthy subjects. We aimed to investigate whether PD patients with dyskinesias display body weight alterations and to observe any correlations between medication and other putative determinants.
Methods:  Charts of 166 PD patients with fluctuations and dyskinesias, admitted within 6 months to a German movement disorders clinic, were investigated for body mass index (BMI), age at onset, disease duration, Unified Parkinson's Disease Rating Scale motor score, eating coordination and medication.
Results:  Analysis showed that 4.2% of PD patients were underweight (BMI < 18.5 kg/m²), 46.4% were normal (BMI > 18.5–25 kg/m²), 33.7% were overweight (BMI > 25–30 kg/m²), 15.7% were obese (BMI > 30 kg/m²). Daily levodopa dosage per kg and total dopaminergic dosage per kg body weight were negatively correlated with BMI. Overall, patients' BMI had not significantly changed within 2 years of follow-up.
Conclusions:  In sum, advanced PD patients showed a reduced BMI when compared with a control population obtained from an age-matched group taken from a survey of the German Federal Office for Statistics. Our findings indicate that patients with a lower BMI received a higher cumulative levodopa dosage and that levodopa may be responsible for weight loss in PD.     

Combining entacapone with levodopa/DDCI improves clinical status and quality of life in Parkinson’s Disease (PD) patients experiencing wearing-off,regardless of the dosing frequency: results of a large multicentre open-label study

Summary. The efficacy of entacapone and its impact on patient quality of life (QOL) was investigated in an open-label study of 899 patients with idiopathic Parkinsons Disease (PD) experiencing wearing-off fluctuations. Patients were divided into 3 groups (3, 4 or 5 doses daily) based on their current levodopa dosage frequency. Patients received 200mg entacapone with each levodopa/dopa-decarboxylase inhibitor (DDCI) dose, while continuing their same levodopa/DDCI dosage regimen for 4 weeks. Primary efficacy measure was the Investigators Clinical Global Impression of Change (CGIC). Patient QoL was assessed using the validated 8-item Parkinsons Disease Questionnaire (PDQ-8). Investigators CGIC revealed that 76.5% of entacapone treated patients experienced an improvement in global status after 4 weeks. Treatment with entacapone was also associated with improvement in patient QoL, with a mean reduction (improvement) in PDQ-8 score of 1.8 from baseline. This study confirms and extends the results of earlier studies demonstrating that, independent of dosing frequency, completing levodopa/DDCI therapy with entacapone provides clinically relevant improvements in global status and QoL in PD patients experiencing wearing-off on their current levodopa dosing frequency.     

Platelet monoamine oxidase-B activity in Parkinson's disease

Summary Platelet MAO-B levels have been investigated in seventeen consecutively diagnosed and previously untreated patients with idiopathic Parkinson's disease using the non-hydroxylated catecholamine, -phenylethylamine, as substrate. Patients with Parkinson's disease had MAO-B activity levels that were considerably higher than sex and age matched normal controls or patients with Motor neurone disease or Myasthenia gravis.     

Visuoperception and visuospatial and visuorotational performance in Parkinson's disease

Summary Forty patients with Parkinson's disease were compared with 33 normal controls with respect to their performance in the Wechsler Adult Intelligence Scale subtests information, similarities, block design, and picture completion, in a test for visual neglect (Hamsher's line cancellation test) and in tests for visuospatial and visuorotational abilities (cube task from Amthauer's intelligence structure test and Rybakoff figure test, as revised by Meili). The findings show that the patients scored significantly worse than the controls (Mann-WhitneyU test,P=0.004) in the Rybakoff figure test, testing visual concept finding, imagination and visual rotation. In the other tests no significant differences were found between the patients and the controls. The deficit of the patients in the figure test of Rybakoff correlated significantly with tremor (P=0.013), akinesia (P=0.009), disability (P=0.043), and age (P=0.004, Spearman rank correlation).     

A 10 year retrospective audit of long-term apomorphine use in Parkinson’s disease

Abstract Objectives Apomorphine is a potent dopamine agonist useful in the treatment of Parkinsons disease patients with disabling motor fluctuations and off periods, not responding to oral medication. It can also be of benefit in reducing dyskinesia by providing more constant dopaminergic stimulation and permitting lower levodopa dosage. However, there is a paucity of information on long-term benefits of apomorphine, including no large-scale phase III trial. We have examined our experience of apomorphine over the last 10 years, to assess indications, pattern of use, efficacy, and side effect profile. Methods All patients requiring apomorphine were identified through the Parkinsons disease Nurse Specialists records. An audit form was produced so that the same information was gathered from all case-notes. Results There were 107 patients (61 males and 46 females). Mean age of disease onset was 50.9 years, SD±9.3 (range 29–78). The mean duration of disease at start of apomorphine treatment was 10 years (SD±4.8, range2–29). The most common indications for apomorphine were severe unpredictable off periods (75.7 %), motor fluctuations (18.7 %) and dyskinesia (5.6 %). Most patients (63.6 %) used both intermittent subcutaneous injections and infusion via pump; 25.2% were on intermittent injection, and 11.2 % infusion alone. Mean dose per injection was 3.7mg. Mean infusion dose 69.8mg, running over a mean of 13.5 hours. The mean duration of intermittent apomorphine use was 48.2 months. The mean duration of infusion was 25.1 months. Complications included skin problems in 16 patients, 2 had symptomatic hypotension, 2 worsening confusion, 1 new confusion and 5 new hallucinations (after sometime on apomorphine). Sixteen patients have stopped using apomorphine completely. Thirteen have stopped the pump, but continue on intermittent injections. Conclusion Subcutaneous apomorphine is easy for patients to use, is well tolerated and has a low incidence of side effects, especially confusion.