How parkinsonism influences life: the patients' point of view.

To explore the experience of living with parkinsonism, a survey form was sent to the members of a patients' association; 1,256 forms were analysed. The mean age was 65.75 ± 9.29 years; 64.4% males. A family history was reported by 19.2%. Basic abilities were preserved in 75% of the responders; the ability to do indoor and outdoor activities was preserved in 42 and 28%, respectively. 70% of the responders liked to meet other people and about 50% liked discussing their condition. 80.3% of the responders lived with partner, while 7.8% did not live with family. Of the patients' partners, 38.9% took drugs, and 9.4% themselves needed assistance. Care programmes for parkinsonians should take into account the disease duration, the degree of disability, the presence of caregiver/s, and the level of caregiver burden; but it should also be appreciated that social habits, need of help, and severity of symptoms influence disability.

Comorbid disorders and hospitalisation in Parkinson's disease: a prospective study.

Parkinson's disease (PD) is often associated with other disorders, typical of the disease or of the age of PD patients, that can lead to hospitalisation, sometimes as emergencies. In this one-year prospective, longitudinal study, we investigated the comorbid events prompting the hospitalisation, or occurring during the planned hospitalisation, of an unselected group of 180 PD patients, admitted to 9 general hospitals in the course of the study. The most frequent acute comorbid events were trauma (30.5%), mostly due to falls, and vascular disorders (29.3%). Comorbidities were closely related to PD in 50% of cases. More than 50% of patients did not require (in addition to PD therapy) specific treatment for the acute comorbid event. Older age was associated with increased risk of complications. The setting up of multidisciplinary networks covering entire territories could help to improve the way in which we tackle the clinical and social problems generated by PD and its comorbidities.

Peripheral markers of oxidative stress in Parkinson's disease. The role of L-DOPA.

Oxidative stress plays a central role in the pathogenesis of Parkinson's disease (PD). L-DOPA, the gold standard in PD therapy, may paradoxically contribute to the progression of the disease because of its pro-oxidant properties. The issue, however, is controversial. In this study, we evaluated peripheral markers of oxidative stress in normal subjects, untreated PD patients and PD patients treated only with L-DOPA. We also measured platelet and plasma levels of L-DOPA, 3-O-methyldopa (the long-lasting metabolite of the drug), and dopamine. We found that isolated platelets of treated PD patients form higher amounts of 2,3-dihydroxybenzoate, an index of hydroxyl radical generation, than platelets of controls or untreated patients. In treated patients, platelet levels of 2,3-dihydroxybenzoate were positively correlated with platelet levels of L-DOPA, 3-O-methyldopa, and with the score of disease severity. Disease severity was correlated with platelet and plasma levels of L-DOPA, as well as with the daily intake of the drug. No significant differences in platelet levels of cytosolic and mitochondrial isoforms of the antioxidant enzyme superoxide dismutase were found between PD patients, either treated or untreated, and controls. Our findings lend further support to the hypothesis that L-DOPA might promote free radical formation in PD patients.

Is seborrhea a sign of autonomic impairment in Parkinson's disease?

An increase of sebum excretion rate (SER) is frequently observed in patients suffering from Parkinson's disease (PD). Some authors attribute it to the hyperactivity of the parasympathetic system, while others consider the possible action of androgens or of MSH-hormone. The aim of our study was to verify and quantify SER in 70 parkinsonian patients and compare it with SER in 60 normal subjects. We found higher values of SER in male subjects, both in normal and in parkinsonian patients. The highest rate of excretion was observed in parkinsonian males, in agreement with the possible main role of androgens or testosterone in sebum excretion, while the phenomenon did not appear to be related to abnormalities of the autonomic nervous system. The association of PD and sex hormones might therefore be crucial for the developing of seborrhea.

Effect of 8-day therapy with propionyl-L-carnitine on muscular and subcutaneous blood flow of the lower limbs in patients with peripheral arterial disease.

The efficacy of propionyl-L-carnitine in increasing walking capacity in patients with peripheral arterial disease is primarily due to the metabolic effect of the drug, but a direct vasoactive action is also hypothesized. Muscular and subcutaneous blood flow of lower limbs were separately evaluated using the 133-Xenon washout technique in 10 patients with peripheral arterial disease of moderate degree, before and after 8-days of treatment with propionyl-L-carnitine (1 g orally b.i.d.). After treatment, muscular blood flow slightly increased, from 10.7 +/- 13.4 to 14.1 +/- 14.0 ml kg-1 min-1. This increase was not statistically significant (T = -1.6568, P = 0.136). Subcutaneous blood flow was not affected by the treatment (from 26.2 +/- 16.9 to 26.1 +/- 12.5 ml kg-1 min-1, T = 0.0141, P = 0.95). In conclusion, in patients with peripheral arterial disease, short-term therapy with propionyl-L-carnitine had no clinical significant effect on muscular and subcutaneous blood flow of the lower limbs. Therefore, this study suggests that the beneficial effect of this drug on the walking capacity of patients with peripheral arterial disease is not due to a direct vasoactive action. Oral administration of propionyl-L-carnitine was found to be safe, as it did not cause any change in heptic, renal or metabolic functional parameters.

Terguride in stable Parkinson's disease.

Terguride (TER) (2 mg/day) was compared with a placebo in 41 stable Parkinson's disease (PD) patients, so as to test its efficacy as an add-on treatment to spare levodopa (LD). After the 4th week of add-on treatment, LD was reduced by about 25%. The number of "stable" patients (--those with an increase of no more than 20% of the basal Columbia University Rating Scale (CURS) score--remaining after LD reduction was used to compare the two add-on treatments. Most patients, remained "stable" in spite of LD reduction, and no significant differences between the therapies were discovered; the CURS score decreased over time only in the TER group. Hence, TER was shown to be a drug that has DA-ergic properties but with minimal antiparkinsonian efficacy.

"Off" painful dystonia in Parkinson's disease treated with botulinum toxin.

The "off" painful dystonia (OPD), usually concerning the feet, is a type of abnormal involuntary movement, induced by the chronic use of levodopa. It is mostly observed in the advanced stage of Parkinson's disease (PD), particularly in the early morning, in the evening, and late at night. Indeed, some patients have experienced OPD also during "on" periods when dystonic posture of the foot alternates with dyskinesia. The pain probably is due to sustained muscle contraction, which causes prolonged muscle spasm, as in primary dystonia or torticollis. Dopaminergic drugs like bromocriptine, pergolide, and especially apomorphine (s.c. infusions, or bolus), can dramatically improve the OPD. Anticholinergics baclofen and lithium are alos used in the management of OPD with some benefit. On the other hand, clinical experience shows that in many cases, these therapeutic procedures are not always enough to produce the expected results. Thirty PD patients (22 men and eight women) with OPD of the foot were treated with botulinum toxin (Botox, Btx) using electromyograms to guide injections. Dystonia was evaluated using a quantitative rating scale. The selection of the muscles for Btx treatment was carried out on the basis of foot posture. We injected Btx into tibialis posterior, tibialis anterior, gastrocnemius, flexor digitorum longus, and extensores hallucis longus with a median dose 40 IU for each muscle, distributed in two sites. In all patients, the pain improved within 10 days, whereas in 21 patients, the pain disappeared completely for 4 months (range, 3-7 months); a concomitant improvement in intensity of the dystonic spasm was also observed. No side effects were reported. Seven patients with associated "on" foot dystonia described an improvement of foot posture on walking. In conclusion, in this uncontrolled study, the use of Btx in OPD seemed a promising tool to improve pain linked to foot dystonia; however, because of the well-known underlying dopaminergic defect in OPD, the Btx therapy should be considered only if the dopaminergic treatment established for the management of OPD has failed.

Autonomic disorders in Parkinson's disease.

Patients with idiopathic Parkinson's disease (IPD) often show signs and symptoms of autonomic involvement, related to the disease itself or to its progression. The more frequently disturbances reported are connected with loss of extrapyramidal motor control, i.e. dysphagia, gastric emptying and the most common constipation. They concern about 73% of the patients. A high frequency of urinary symptoms, ranging from 37% to 71%, is also reported in IPD, in particular detrusor hyperreflexia causing urgency, frequency of micturing or urgency incontinence. Another autonomic groups of symptoms are related to the failure of cardiopressor adaptability which involve 15% of the subjects and are more typical of late onset cases or forms bordering with the Multiple System Atrophy, finally resulting in orthostatic hypotension (OH).

Comparison between the effect of L-propionylcarnitine, L-acetylcarnitine and nitroglycerin in chronic peripheral arterial disease: a haemodynamic double blind echo-Doppler study.

The haemodynamic effects on the peripheral vascular bed of L-acetylcarnitine, L-propionylcarnitine, and nitroglycerin were tested by echo-Doppler in a double blind cross-over study. Eleven male patients suffering from peripheral arterial obliterative disease (PAOD) in the second stage of Fontaine's classification, and 11 matched control subjects were enrolled in the study. Each subject received one of three different treatments on each day of the study in a different order following a random assignment. The treatments were either 30 mg x kg of L-acetylcarnitine (LAC) or 30 mg x kg of L-propionylcarnitine (LPC) or nitroglycerin (NTG) 1.25 mg given as a single i.v. bolus injected over 3 min. Echo-Doppler measurements of blood flow velocity, and cross-sectional area of the femoral artery were performed at baseline and 10, 20, and 30 min after injection of the drugs. Pulsatility Index (an index derived from the blood flow velocity and related to vascular resistance: PI = Vmax - Vmin/Vmean) was also obtained each time. Results were analysed using a Student's t-test for paired data. L-acetylcarnitine and L-propionylcarnitine showed no haemodynamic effects in either group of subjects (controls and PAOD patients) whether blood flow or vascular resistance was considered. There were haemodynamic changes (a decrease in blood flow velocity and an increase in arterial systemic resistance) only after NTG administration. The changes were more evident in controls than in PAOD patients. Femoral artery cross-sectional area showed no statistically significant effect as regards treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Terguride in fluctuating parkinsonian patients: a double-blind study versus placebo.

Terguride (TER), a semisynthetic derivative of lisuride, has been found to display dopamine (DA) agonist and DA antagonist effects in animals, depending on the experimental model used. TER (2 mg/day) was compared to placebo in 41 fluctuating Parkinson's disease patients to test its effect on akinesia and dyskinesia. Mean hours "off" decreased at weeks 6 and 12 (p < 0.05) in the TER group but the overall difference from the placebo group was not significant. Only the TER group displayed a decrease over time in mean Columbia University Rating Scale total score "on" and "off" (p = 0.001 and p = 0.03, respectively). Duration of involuntary movements and resulting disability were not significantly different between patients on TER and those on placebo administration. In the overall evaluation, patients preferred TER (p = 0.01). Tolerance of TER was very good in all but one patient whose wearing-off increased; no one dropped out because of side effects. This 3-month double-blind study showed that TER, added to stable doses of L-dopa, may have slight antiparkinsonian efficacy.

Superiority of L-propionylcarnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease: an acute, intravenous, double-blind, cross-over study.

The effects of L-propionylcarnitine on walking capacity were assessed in a group of patients with peripheral vascular disease. In 12 patients, 300 mg of L-propionylcarnitine, given intravenously as a single bolus did not affect walking capacity, while 600 mg increased both initial claudication distance from the placebo value of 179 +/- 114 to 245 +/- 129 m (P less than 0.05), and maximal walking distance from 245 +/- 124 to 349 +/- 155 m (P less than 0.05). Once the efficacious dose of L-propionylcarnitine was assessed, its effect was compared to that of an equimolar dose of L-carnitine (500 mg i.v.) according to a double-blind, double-dummy, cross-over design. In 14 patients, both treatments improved walking capacity; however, the analysis of variance showed that the increase in maximal walking distance with L-propionylcarnitine was greater than that with L-carnitine (P less than 0.05). Finally, in seven additional patients, the effects of L-propionylcarnitine and L-carnitine on the haemodynamics of the affected limb were assessed by an ultrasonic duplex system. Results indicated that both drugs did not affect the blood velocity and the blood flow rate in the ischaemic leg, thus suggesting that the beneficial effect on walking capacity was dependent on a metabolic effect. In conclusion, L-propionylcarnitine improves walking capacity in patients with peripheral vascular disease, probably acting through a metabolic mechanism. On a molar basis, this beneficial effect is greater than that observed with L-carnitine and, thus, the findings of the present study may have clinical relevance in terms of treatment cost and patient compliance.

Acute systemic and splanchnic haemodynamic effects of L-carnitine in patients with cirrhosis.

L-carnitine (L-C) is a naturally occurring substance in mammalian tissues that has recently been proposed as a therapeutic agent in hepatic encephalopathy and liver steatosis. L-C also produces some acute, non-metabolic, haemodynamic effects that have not previously been studied in patients with cirrhosis. Therefore, the authors evaluated the acute effect of i.v. administration of L-C (30 mg/kg) on systemic and splanchnic haemodynamics in ten patients (L-C group) with chronic liver disease (Child-Pugh's class A: 4, B: 3, C: 3 patients) and a control group composed of ten patients with similar clinical characteristics (Child-Pugh's class A: 5, B: 2, C: 3 patients) who received placebo. Heart rate, cardiac index and pulmonary arterial pressure (measured by right heart catheterization) decreased slightly but significantly in the L-C group and the changes observed in stroke volume were highly correlated to the Pugh's score. Moreover, the hepatic venous pressure gradient (measured by hepatic vein catheterization) decreased significantly in the L-C group, whereas no changes occurred in the placebo group. The overall response to L-C was contradictory to that previously observed in animals and humans with normal liver function, and the extent seemed to depend on the severity of liver disease. The effect of the drug on cardiac index, heart rate and hepatic venous gradient could possibly be beneficial for patients with hyperdynamic circulatory condition and portal hypertension.