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Cabergoline is a potent D2 receptor agonist with a half-life of 65 hours that may provide continuous dopaminergic stimulation administered once daily. In this study, we randomized de novo Parkinson's disease (PD) patients to treatment with increasing doses of cabergoline (0.25 to 4 mg/d) or levodopa (100 to 600 mg/d) up to the optimal or maximum tolerated dose. Decreases of > 30% in motor disability (Unified Parkinson's Disease Rating Scale Factor III) versus baseline were considered indicative of clinical improvement. If 30% improvement was not achieved, levodopa/ carbidopa could be added on an open basis. Of the 208 patients entered in the cabergoline group, 175 remained in the study for 1 year at a mean dose of 2.8 mg/d; in the levodopa group, 176 of the 205 patients entered were still on study after 1 year at a mean dose of 468 mg/d. The proportion of patients requiring additional levodopa/carbidopa increased in the cabergoline group from 18% at 6 months to 38% at 1 year versus 10% (p = 0.05) at 6 months and 18% (p < 0.01) at 1 year in the levodopa group. The proportion of patients showing clinical improvement did not differ significantly between the two groups, or between the subgroups on monotherapy, at any endpoint. Irrespective of levodopa/carbidopa addition, 81% of patients in the cabergoline group and 87% of patients in the levodopa group were clinically improved at 1 year (p = 0.189); the corresponding figures for the subgroup on monotherapy were 79% in the cabergoline-treated patients and 86% in the levodopa-treated patients (p = 0.199). The mean difference versus baseline in Unified Parkinson's Disease Rating Scale Factor III scores in patients who remained on monotherapy up to 1 year was 12.6 (95% confidence interval [CI]: 10.8, 14.3) in the cabergoline group and 16.4 (95% CI: 14.8, 18.0) in the levodopa group. Adverse events occurred in 76% of patients on cabergoline and in 66% of patients on levodopa. The severity profile for reported events was similar for the two agents. The results of this study indicate that cabergoline treatment for up to 1 year is only marginally less effective than levodopa in the proportion of patients who can be treated in monotherapy. More than 60% of de novo PD patients could be managed on cabergoline alone up to 1 year. In the patients in whom levodopa/carbidopa was needed, the combination therapy provided efficacy similar to that obtained with levodopa alone, with a relevant sparing of levodopa.

This study showed that, compared with levodopa, initial therapy with cabergoline in patients with Parkinson's disease is associated with a lower risk of response fluctuations at the cost of a marginally reduced symptomatic improvement and some tolerability disadvantages that are mostly limited to a significantly higher frequency of peripheral oedema.

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Six patients with Friedreich's ataxia, 4 males and 2 females, their ages ranging from 13 to 33 years, were studied. The early manifestations started between age 7 and 13 with an evolution time between 6 and 20 years. Serial visual and brain stem auditory evoked potential recordings were made. A progressive increase in latency, reduction in amplitude and in latency inter-ocular difference ofPlOO were observed. The pattern of the reversal checker-board visual evoked potential was preserved. A disorganized BAEP pattern, a well defined potential I, a very small potential V and a delay in the interpeak latency were constant findings. The assumption is made of a progressive involvement of both visual and central auditory pathways. Pathophysiological mechanisms are discussed. RESUME: Six patients avec ataxie de Friedreich, 4 hommes et 2 femmes, ages de 13 a 33 ans, furent etudies. Les premiers signes debutent de 7 a 13 ans avec une periode d'evolution de 6 a 20 ans. Des potentiels evoques visuels et auditifs du tronc cerebral furent faits en serie. Nous avons note une augmentation progressive dans la latence, une reduction de I'amplitude et de la difference de latence inter-oculaire du PI00. Le pattern du potentiel evoque visuel fut cependant conserve. De fa?on constante nous avons retrouve un pattern BAEP desorganise, un potentiel 1 bien defini, un tres petit potentiel V et un retard dans la latence interpics. Nous croyons done a une atteinte progressive des voies visuelles et auditives centrales dans cette maladie. Nous en discutons la pathophysiologic.

Fourteen parkinsonian patients, 10 of them showing severe and long-standing ‘on-off effects and 4 ‘end-of-dose impairment’, received Madopar HBS instead of standard Madopar. At the end of the dosage adaptation phase (9 weeks) most patients improved; in patients with ‘on-off phenomenon, parkinsonism became less severe, on periods were longer, and fluctuations decreased; end-of-dose impairment resolved in 4 patients. However, a longer delay in the onset of the therapeutic effect was observed after the first daily drug intake in those patients still showing severe early-morning parkinsonism. With Madopar HBS, L-dopa dosage was increased by 116 %. In spite of a greater dopaminergic effect, dyskinesias were reduced, and dystonias became less marked or even disappeared.

Thirteen parkinsonians with a long duration of the disease and longterm dopa therapy, seven of them showing severe on-off oscillations and 6 an "endof-dose impairment", were treated with a controlled release (HBS) preparation of L DOPA/benserazide for more than 3 years.Thereafter, selegiline was added in a progressively increasing dosage up to a maximum of 10 mg/day during 4 months, with the aim of a) further improving the longterm results and b) reducing the doses of the new formula of LDOPA.A significant decrease of early morning parkinsonism and reduction of motor disability throughout the day were observed; "wearing-off" cases showed better results compared with those presenting "on-off" oscillations. A mean reduction of 20 ' 70 in the doses of levodopa was achieved. Likewise, a mild reduction of dyskinesias and a mild-moderate enhancement of dystonias were recorded. Only one patient did not tolerate selegiline and two others received lower doses due to side-effects.Selegiline was capable of enhancing the antiparkinsonian effect of the new formula of LDOPA, while allowing a reduction of the doses administered. It must also be emphasized that such improvement was achieved in complicated patients, most of whom showed some deterioration of response in the late stages of long-term sustained-release levodopa treatment.