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Objectives: Cabergoline is an ergoline derivative with a very long half-life that allows once-daily administration and the potential for more continuous stimulation of dopaminergic receptors than is possible with other dopamine receptor agonists (DAs). The aim of this study was to evaluate whether the possible advantage resulting from a more sustained dopaminergic effect of cabergoline would translate into delayed onset of motor complications, compared with levodopa, in patients with newly diagnosed Parkinson's disease., Study Design and Methods: This study was a double-blind, multicentre trial that compared cabergoline and levodopa as initial therapy for Parkinson's disease. A total of 419 levodopa-, DA- and selegiline-naive patients with newly diagnosed Parkinson's disease were randomised to receive either cabergoline (n = 211) or levodopa (n = 209). Treatment was titrated to an optimal dose over a period of up to 24 weeks and then continued at this dose until the study endpoint (confirmed motor complications) or up to a maximum of 5 years. At years 1-5, the cabergoline group was receiving cabergoline at average daily doses ranging from 2.8-2.9 mg, with added levodopa at mean daily doses ranging from 322 mg at year 1 to 431 mg at year 5; over the same period, the levodopa group was receiving daily levodopa doses of 784 mg. Thus, patients in the cabergoline group received <50% levodopa than patients in the levodopa group., Results: Motor complications were significantly delayed (p = 0.0175) and occurred less frequently in cabergoline-treated patients than in levodopa-treated patients (22.3% vs 33.7%). Cox model proportional hazards regression analysis showed that the relative risk of developing such complications was >50% lower (0.46; p < 0.001) in the cabergoline group compared with the levodopa group. In particular, development of dyskinesias was markedly delayed in the cabergoline group and occurred in 9.5% of patients compared with 21.2% in the levodopa group (p < 0.001). Among patients not requiring supplemental levodopa, the frequency of motor complications was three times higher with levodopa (15.5% of 110 patients) than with cabergoline (5.3% of 76 patients). Among patients who did need supplemental levodopa, motor complications were more frequent in the levodopa arm (54.1% of 98 patients) than in the cabergoline arm (31.9% of 135 patients). Consistent improvements relative to baseline in average Unified Parkinson's Disease Rating Scale (UPDRS) daily living activities and motor function sections, and in Clinical Global Impression severity of illness and physician- and patient- rated global improvement scores, were seen in both treatment groups, with maximal effects occurring within 2 years. However, levodopa treatment was associated with a significantly (p < 0.001) greater improvement in motor disability (as measured by the UPDRS motor score) over time, with mean values of 13.8 versus 12.9 in the cabergoline versus levodopa arm recorded at 1 year, 18.6 versus 17.2 at 3 years and 19.2 versus 16.3 at 5 years, respectively. While the overall frequency of adverse events was similar in the two groups, the cabergoline-treated group experienced marginally, but not significantly, higher frequencies of nausea, vomiting, dyspepsia and gastritis (37.4% vs 32.2% in the levodopa group) and of dizziness and postural hypotension (31.3% vs 24% in the levodopa group). Cabergoline-treated patients also experienced a significantly higher frequency of peripheral oedema (16.1% vs 3.4%, respectively; p < 0.0001). The cabergoline and levodopa groups had similar rates of sleepiness (17.5% vs 18.3%, respectively) and hallucinations (4.8% vs 4.4%, respectively); in an elderly population subset, hallucinations were reported in 7.1% and 6.5% of patients taking cabergoline and levodopa, respectively. Adverse events generally occurred more frequently in female patients (with the exception of dyskinesias, hyperkinesias and hallucinations, which occurred more frequently in men) and in the elderly., Conclusion: 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.

Patients and Methods: We studied five biological fluids which were easily accessible to immunological examination (cerebrospinal fluid, plasma, tears, saliva and urine) in 25 patients with multiple sclerosis, clinically definite according to the criteria of Cleveland, Ohio (1991) and tabulated according to the Kurztke's expanded disability status scale. The samples were obtained simultaneously during a clinical bout of the disease before any pharmacological or immunosuppressive treatment had been given., Results: The soluble interleukin-2 levels were significantly raised in at least three of these fluids--always absent from the urine--when compared with normal controls. The sensitivity and specificity of this determination for diagnosis of the condition was greater than that of other immunochemical parameters--oligoclonal distribution of immunoglobulins (specifically of IgG), imbalance of the light Kappa and Lambda chains--and physiological studies (evoked potentials). The dosification and quantification of basic myelin protein of the central nervous system, rich in citruline in the urine, may be a parameter of progressiveness., Conclusion: This methodology (five humours test) may be used to establish an earlier, more certain diagnosis of multiple sclerosis and also monitor its biological activity together with nuclear magnetic resonance with intravenous contrast.

1. Of 22 parkinsonians with fluctuations under long-dating dopatherapy in whom standard Madopar was substituted by the HBS form, 16 who performed the trial longer than 1 year were particularly studied to evaluate some parameters of this long-term follow-up (30-36 months). 2. The outstanding beneficial effects were an enhancement of the antiparkinsonian response, improvement or disappearance of motor oscillations, longer "on" periods, less severe "off" periods, and a more sustained nocturnal antiparkinsonian effect with a reduction of dystonias and pain at night and decreased or absent early morning parkinsonism. 3. The decrease or disappearance of dystonia was observed since the early stages of the trial and can be explained by the more sustained dopaminergic effect. 4. Surprisingly, dyskinesias also decreased in spite of the higher dopaminergic effect. The avoidance of sharp and repeated plasmatic peaks and the lower levels of L-dopa under HBS could explain this phenomenon. 5. The negative aspects of Madopar HBS are a lower bioavailability that means a dosage increase and a longer latency for the therapeutic response in the morning. 6. The dosage increase went up by 80% to 100% in relation to standard Madopar during the long-term treatment. 7. As Madopar HBS is a sustained release preparation, we had to increase the initially reduced the number of intakes, again in order to obtain better results. In the most severe cases with poor or absent response, benefits were achieved only when administering the HBS intake every hour.(ABSTRACT TRUNCATED AT 250 WORDS)

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 decrease; 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.

Four members of a family with consanguineous relationships, the proband and his three children (2 sons and 1 daughter) are affected with Familial Spastic Ataxia and with Ehlers-Danlos' Syndrome with platelet aggregation dysfunction. In the four cases, this exceptional association appears remarkably homogeneous both in clinical and laboratory studies. The two syndromes are of dominant-autosomic transmission and probably originated in a new mutation which presumably maintained a genetic linkage. Spastic ataxia is characterized by a precocious onset and a slow evolution. The first-born son shows a dominant pyramidal syndrome with mild ataxia suggesting that it is a transitional form of familial spastic paraplegia. The Ehlers-Danlos syndrome pertains to form II or "mitis" with moderate skin hyperelasticity and joint hypermobility. The abnormal platelet aggregation curves have the same profile in all the patients. The first-born son also presents a mitral valve prolapsus as we may find either in Ehlers-Danlos syndrome or in spastic ataxia. The neurophysiological, tomographical, histological, ultrastructural and biochemical studies attempt to accomplish a better definition of these associated nosological entities.

A group of 71 patients with Parkinson's disease were treated with L-Dopa and benserazide during periods ranging from 27 to 60 months. In 28% of cases a decline in therapeutic effects and or delayed appearance or increase of secondary actions were observed constituting a long-term syndrome. Its most complex and dramatic expression, the on-off effect, was present in 11% of cases. Those patients with more severe symptoms were studied by means of continuous clinical observation enabling the design of daytime follow-up curves. Observations were repeated with varying dosage patterns, showing variations but no substantial changes or disappearance of the symptoms described. Electromyographic recordings and films were taken in certain cases defining the characteristics of on and off effects. Several procedures were implemented in an attempt to control Long-Term Syndrome manifestations: Change of dosage, variation of L-dopa/decarboxilase inhibitor ratio, association of anticholinergic agents with antidepressants, hypoprotein diets. Improvement was moderate and/or transient, with the exception of Nortriptilline which permitted total or partial control of certain symptoms, especially hypokinetic periods, bouts of tremor and dystonic attitudes. It was occasionally necessary to interrupt administration of L-Dopa, readministering it later with recovery of the therapeutic effect and/or avoidance of undesirable effects for varying periods of time. Loss than optimal doses proved beneficial in reducing or postponing Long-Term Syndrome manifestations. Although L-Dopa does not detain the course of the disease, the persistence of favourable results in most patients for prolonged periods of treatment confirms the long-term therapeutic value of this drug.

In 28% of patients treated for a long time with L-dopa, alone or combined with a decarboxilase inhibitor, the following "long-term syndrome" was observed: decrease in effectiveness, psychic disorders, intense abnormal movements, distonic attitudes, speech and gait disorders, orthostatic hypotension and/or general reprecussion. In 11% of the patients the "on-off" effect was studied (brisk alteranting Parkinsonic and improved states). Clinical observation during 14 hours a day was repeated with different dosages and different regimes of the drug; these modified the daily variations but did not eliminate the syndrome. The electromyographic studies also revealed the "on and off" phenomenon in different patients. When the "long-term syndrome" is severe, at times it is necessary to stop the drug; the secondary effects are thus decreased and, when the medication is given again, the therapeutic effectiveness is temporarily restored. When the drug is stopped the patients should be watched, since a "withdrawal syndrome" may appear.

Twenty-five patients with various forms of dyskinesia were given tiapride for three months. Maximal dosage was 900 mg per day. A double-blind trial of tiapride versus placebo showed significantly better results in the group given tiapride. The forms of dyskinesia which responded best to tiapride were the following: iatrogenic dyskinesia, tics (Gilles de la Tourette syndrome), and chronic chorea (Huntington disease). Patients with complex dyskinesia resulting from neonatal encephalopathy or vascular disease were not improved. The protocol used in l-dopa-induced dyskinesia is described. Changes in dyskinesia and "on-off" effect following variations in tiapride and l-dopa dosage are detailed. An unequivocal, although minor, tiapride-induced parkinson syndrome was recorded in a few patients. No instances of tiapride-induced dyskinesia or akathisia were seen. The other side-effects were either psychic (depression, drowsiness, agitation) or endocrinologic (menstrual disorders, overeating, galactorrhea).

The authors present an exceptional case of chemodectoma jugulare with important invasion of the skull base involving all the cranial nerves on one side and conforming Garcin's syndrome. Practically all the possible ways of spreading were followed by the tumor, with involvement of the posterior, middle and anterior fossas of the skull base and also orbit, middle ear and neck. The clinical and histopathological difficulties in the diagnosis, especially when the chemodectoma has only neurological signs, are stressed. The association of otologic symptoms makes the diagnosis easier. The patient had an early onset of the symptoms and a rapid evolution considering this type of tumors. The appearance of goitre in this patient is a sign of endocrine disturbance, which is occasionally associated with these tumors. Apparently this chemodectoma was not a secreting tumor, since the blood pressure values were normal. No signs of multicentricity or metastatic growths were detected. The radiological studies, and especially computerized tomography scanning, gave precise information about the spreading of the tumor. The authors consider that the knowledge of this entity is important in order to arrive at a correct diagnosis.

Eighty-one Parkinsonic patients were treated with L-dopa alone and/or combined with Ro4-4602, during 27 to 60 months. The results are reported. 7.2% of the patients, who are still being treated, showed good, very good or excellent results. There was a relation between the duration of the illness and the degree of improvement, the most prolonged Parkinsonisms showed the least improvement. The 4:1 proportion of L-dopa and Ro4-4602 was more effective than the 3:2. Adding small amounts of L-dopa to the combinations improvement and secondary effects increased. No advantages were found using high combined dosages. The main secondary effects at the end of treatment were abnormal movements (45% of cases) and distonic attitudes (53%). Patients who stoped the medication showed less sustained improvement and a high degree of Parkinsonism. This reveals that Parkinson's disease continues to envolve in spite of the medication. The "long-term syndrome" includes the late decrease of effectiveness of the drugs and/or the increase of secondary effects.

Lhermitte-Duclós disease is an infrequent condition of which there are only 37 cases described in the literature. Although presently considered as a displasic process, its clinical presentation is of a typical posterior fossa tumour and should be treated as such. Even though it is a benign growth there are only 7 cases described with postoperative survival. The uniform pathological anatomy in all the cases presented makes the definitive diagnosis. The authors present a new case with postoperative survival and discuss its clinical presentation, treatment and origin of the disease.