RESUMO
OBJECTIVE: To evaluate the association of the rs11125908 polymorphism in the COMMD1 gene in the Cuban population with rheumatoid arthritis (RA). METHODS: In this case-control study, 161 RA patients and 150 control subjects were genotyped for rs11125908 by the allele-specific polymerase chain reaction method. DNA sequencing was used to verify the assignation of the polymorphism. The odds ratios (OR) and their 95% confidence interval were calculated by logistic regression to determine the associations between genotypes and RA using the SNPStats software. RESULTS: An association of the single nucleotide polymorphism with the disease was found in the overdominant model (p=0.025; OR=1.91) for the AG genotype. Our analyses revealed an association between rs11125908 and the subgroup of patients with swollen joints < median under the codominant model for AG (p=0.034; OR=2.30) and GG genotype (p=0.034; OR=0.82) and with the overdominant model (p=0.01; OR=2.38). The subgroup of patients with an age of onset lower than the mean and AG genotype showed an association in the overdominant model (p=0.027; OR=2.27). Disease activity score 28 with erythrocyte sedimentation rate and disease duration variables were not associated with the rs11125908 polymorphism. CONCLUSIONS: rs11125908 was associated with RA and with the number of swollen joints and age of onset subgroup analyses. We provide concepts for treatments for RA, based on pharmacological management of COMMD1 expression.
Assuntos
Artrite Reumatoide , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Adaptadoras de Transdução de Sinal/genética , Artrite Reumatoide/genética , Estudos de Casos e Controles , Cuba , Predisposição Genética para Doença , GenótipoRESUMO
BACKGROUND AND PURPOSE: The presentation of Parkinson's disease patients with mutations in the LRRK2 gene (PDLRRK2 ) is highly variable, suggesting a strong influence of modifying factors. In this context, inflammation is a potential candidate inducing clinical subtypes. METHODS: An extensive battery of peripheral inflammatory markers was measured in human serum in a multicentre cohort of 142 PDLRRK2 patients from the MJFF LRRK2 Consortium, stratified by three different subtypes as recently proposed for idiopathic Parkinson's disease: diffuse/malignant, intermediate and mainly pure motor. RESULTS: Patients classified as diffuse/malignant presented with the highest levels of the pro-inflammatory proteins interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 1-ß (MIP-1-ß) paralleled by high levels of the neurotrophic protein brain-derived neurotrophic factor (BDNF). It was also possible to distinguish the clinical subtypes based on their inflammatory profile by using discriminant and area under the receiver operating characteristic curve analysis. CONCLUSIONS: Inflammation seems to be associated with the presence of a specific clinical subtype in PDLRRK2 that is characterized by a broad and more severely affected spectrum of motor and non-motor symptoms. The pro-inflammatory metabolites IL-8, MCP-1 and MIP-1-ß as well as BDNF are interesting candidates to be included in biomarker panels that aim to differentiate subtypes in PDLRRK2 and predict progression.
Assuntos
Inflamação/etiologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Doença de Parkinson/genética , Doença de Parkinson/patologia , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Quimiocina CCL2/sangue , Quimiocina CCL4/sangue , Estudos de Coortes , Citocinas/sangue , Progressão da Doença , Feminino , Humanos , Inflamação/genética , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , MutaçãoAssuntos
Malformações Vasculares do Sistema Nervoso Central/terapia , Dimetil Sulfóxido , Embolização Terapêutica/métodos , Polivinil , Aneurisma Roto/etiologia , Aneurisma Roto/terapia , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Angiografia Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Punções , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Although central nervous system (CNS) involvement in adult myotonic dystrophy type 1 (DM1) was described long ago, the large number of variables affecting the cognitive and personality profile have made it difficult to determine the effect of DM1 on the brain. The aim of this study was to define the cognitive and personality patterns in adult DM1 patients, and to analyse the relationship between these clinical patterns and their association with the underlying molecular defect. METHOD: We examined 121 adult DM1 patients with confirmed molecular CTG repeat expansion and 54 control subjects using comprehensive neuropsychological tests and personality assessments with the Millon Clinical Multiaxial Inventory (MCMI)-II. We used a multiple linear regression model to assess the effect of each variable on cognition and personality adjusted to the remainders. RESULTS: Patients performed significantly worse than controls in tests measuring executive function (principally cognitive inflexibility) and visuoconstructive ability. In the personality profile, some paranoid and aggressive traits were predominant. Furthermore, there was a significant negative correlation between the CTG expansion size and many of the neuropsychological and personality measures. The molecular defect also correlated with patients' daytime somnolence. CONCLUSIONS: Besides muscular symptomatology, there is significant CTG-dependent involvement of the CNS in adult DM1 patients. Our data indicate that the cognitive impairment predominantly affects the fronto-parietal lobe.
Assuntos
Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Distrofia Miotônica/epidemiologia , Distrofia Miotônica/psicologia , Personalidade , Expansão das Repetições de Trinucleotídeos/genética , Adolescente , Adulto , Idoso , Análise de Variância , Southern Blotting/métodos , Transtornos Cognitivos/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/genética , Miotonina Proteína Quinase , Testes Neuropsicológicos/estatística & dados numéricos , Inventário de Personalidade/estatística & dados numéricos , Reação em Cadeia da Polimerase/métodos , Proteínas Serina-Treonina Quinases/genética , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Sequências Repetitivas de Ácido Nucleico , Espanha/epidemiologia , Adulto JovemRESUMO
Mutations in LRRK2 gene are the most frequent cause of Parkinson's disease (PD) described, but their prevalence varies between populations. Patients, 418, with PD and 138 unrelated controls from the Basque Country were screened for LRRK2 G2019S and R1441G mutations. Of the patients, 3.82% were heterozygous carriers of G2019S and 13.15% of R1441G. G2019S frequency was higher in non-Basque population (6.0%), while R1441G was more common in Basque origin population (22.4%). Our conclusion is that both G2019S and R1441G mutations' frequency varies markedly between Basque and non-Basque origin population reinforcing the importance of ethnicity consideration when establishing mutation prevalence.
Assuntos
Mutação , Doença de Parkinson , Proteínas Serina-Treonina Quinases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Pessoa de Meia-Idade , Doença de Parkinson/etnologia , Doença de Parkinson/genética , EspanhaRESUMO
INTRODUCTION: Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) typically arises as an autonomic neuropathy primarily affecting small fibres and it occurs in adult patients in their second or third decades of life. It progresses rapidly and can lead to death in approximately 10 years. Other phenotypes have been described in non-endemic areas. OBJECTIVES AND METHODS: We described 4 cases from the Spanish province of Guipuzcoa, a non-endemic area, to highlight the clinical variability of this disease. PATIENTS AND RESULTS: Three patients presented a late-onset form manifesting after the age of 50, featuring a predominantly motor polyneuropathy initially causing distal impairment of the lower limbs followed by the upper limbs. One patient suffered severe neuropathic pain. None showed signs of autonomic involvement. The fourth patient, of Portuguese descent, presented a typical form with onset in her thirties, neuropathic pain and dysautonomia. All patients carry the Val50Met mutation in the TTR gene. CONCLUSION: FAP is a pleomorphic disease even in patients carrying the same mutation. In non-endemic areas, its main form of presentation may resemble a predominantly motor polyneuropathy developing in the sixth decade of life with no signs of dysautonomia. Given this non-specific presentation and the widely available technical means of studying the TTR gene, we believe that the protocol for the aetiological diagnosis of any polyneuropathy should include genetic sequencing of TTR.
Assuntos
Neuropatias Amiloides Familiares/genética , Amiloidose Familiar/genética , Mutação , Pré-Albumina/genética , Adulto , Idoso , Neuropatias Amiloides Familiares/patologia , Amiloidose Familiar/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Experience with the endovascular treatment of unruptured small intracranial aneurysms by flow diverter devices is still limited. OBJECTIVE: To assess the safety and efficacy of the SILK flow diverter (SFD) in the treatment of small unruptured cerebral aneurysms (<10â mm). METHODS: We performed a retrospective review of a prospectively maintained database of patients treated with a SFD between July 2008 and December 2013 at 4 institutions in Spain to identify all patients with small unruptured aneurysms (<10â mm). Data for patient demographics, aneurysm characteristics, and technical procedures were analyzed. Angiographic and clinical findings were recorded during the procedure and at 6- and 12-month follow-ups. RESULTS: A total of 109 small aneurysms were treated with a SFD in 104 patients (78 women; 26 men; mean, median, and range of age: 55.2, 57.1, and 19-80â years, respectively). A total of 60 patients were asymptomatic (57.7%). All except 7 aneurysms (6.4%) arose from the anterior circulation. The mean size of the aneurysms was 4.7±1.9â mm. At 6â months, the neuromorbidity and neuromortality rates were 2.9% and 0.9%, respectively. Imaging at the 12-month follow-up showed complete occlusion, neck remnants, and residual aneurysm in 88.5% (69/78), 7.7% (6/78), and 3.3% (3/78) of cases, respectively. No delayed hemorrhage occurred. CONCLUSIONS: The findings suggest that the indications for SFD can be safely extended to small intracranial aneurysms.
Assuntos
Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Stents/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Cerebral/métodos , Bases de Dados Factuais , Embolização Terapêutica/métodos , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Parkinson's disease (PD) is the second most common age-related neurodegenerative disease after Alzheimer's disease (AD). Common risk factors for both diseases have been explored to study potential etiologic interactions between these two neurodegenerative disorders. The APOE epsilon4 allele, previously associated with AD, has also been associated with risk of PD and with the presence of some clinical features in PD patients. However, the role of APOE epsilon4 allele in risk of PD remains unclear. We studied the distribution of APOE alleles in 276 unrelated familial and sporadic PD patients and in 212 controls. Patients and controls were classified by ethnicity. No genetic heterogeneity between Basques and people from other regions of Spain was found. No significant differences in APOE allele distribution between PD patients and controls were found; however, lower epsilon4 allele frequency was observed when the sporadic PD group was analyzed separately. By contrast, an increase in epsilon4 allele frequency was found in familial PD patients with cognitive decline. We conclude that the APOE epsilon4 allele may be associated with the risk of developing PD in isolated cases and that it is linked to the presence of cognitive decline in familial PD in our sample.
Assuntos
Apolipoproteínas E/genética , Saúde da Família , Doença de Parkinson/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Alelos , Apolipoproteína E4 , Feminino , Frequência do Gene , Humanos , Masculino , Doença de Parkinson/fisiopatologia , Polimorfismo Genético , RiscoRESUMO
Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), a partial epilepsy characterized by the presence of auditory seizures. However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin, or evidence for linkage to the 10q24 locus. Other authors as well as ourselves have found an internal repeat (EPTP, pfam# PF03736) that allowed the identification of three other genes sharing a sequence and structural similarity with LGI1/Epitempin. In this work, we present the sequencing of these genes in a set of ADLTE families without mutations in both LGI1/Epitempin and sporadic cases. No analyzed polymorphisms modified susceptibility in either the familial or sporadic forms of this partial epilepsy.
Assuntos
Epilepsia do Lobo Temporal/genética , Proteínas/genética , Alelos , Genes Dominantes , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo , Polimorfismo Genético , Análise de Sequência de DNARESUMO
We present here the clinical, molecular and biochemical findings from 238 limb-girdle muscular dystrophy type 2A (LGMD2A) patients, representing approximately 50% (238 out of 484) of the suspected calpainopathy cases referred for the molecular study of the calpain 3 (CAPN3) gene. The mean age at onset of LGMD2A patients was approximately 14 years, and the first symptoms occurred between 6 and 18 years of age in 71% of patients. The mean age at which the patients became wheelchair bound was 32.2 years, with 84% requiring the use of a wheelchair between the age of 21 and 40 years. There was no correlation between the age at onset and the time at which the patient became wheelchair bound, nor between the sex of the patient and the risk of becoming wheelchair bound. Of the cases where the CAPN3 gene was not affected, approximately 20% were diagnosed as LGMD2I muscular dystrophy, while facioscapulohumeral muscular dystrophy (FSHD) was uncommon in this sample. We identified 105 different mutations in the CAPN3 gene of which 50 have not been described previously. These were distributed throughout the coding region of the gene, although some exons remained free of mutations. The most frequent mutation was 2362AG-->TCATCT (exon 22), which was present in 30.7% of the chromosomes analysed (146 chromosomes). Other recurrent mutations described were N50S, 550DeltaA, G222R, IVS6-1G-->A, A483D, IVS17+1G-->T, 2069-2070DeltaAC, R748Q and R748X, each of which was found in >5 chromosomes. The type of mutation in the CAPN3 gene does not appear to be a risk factor for becoming dependent on a wheelchair at a determined age. However, in the cases with two null mutations, there were significantly fewer patients that were able to walk than in the group of patients with at least one missense mutation. Despite the fact that the results of phenotyping and western blot might be biased due to multiple referral centres, producing a diagnosis on the basis of the classical phenotype is neither sufficiently sensitive (86.7%) nor specific (69.3%), although western blot proved to be even less sensitive (52.5%) yet more specific (87.8%). In this case LGMD2I was a relevant cause of false-positive diagnoses. Considering both the clinical phenotype and the biochemical information together, the probability of correctly diagnosing a calpainopathy is very high (90.8%). However, if one of the analyses is lacking, the probability varies from 78.3 to 73.7% depending on the information available. When both tests are negative, the probability that the sample comes from a patient with LGMD2A was 12.2%.
Assuntos
Calpaína/genética , Isoenzimas/genética , Proteínas Musculares/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Adolescente , Adulto , Idade de Início , Teorema de Bayes , Western Blotting , Criança , Análise Mutacional de DNA/métodos , Progressão da Doença , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/epidemiologia , Mutação de Sentido Incorreto , Fenótipo , Estudos RetrospectivosRESUMO
Dementia lacking distinct histopathological features (DLDHF) belongs to the frontotemporal dementia syndromes. Behavioral, cognitive and motor symptoms are its usual clinical manifestations. However, considerable heterogeneity exists and no evident clinicopathological correlations can be performed. We report a patient who presented with a very unusual combination of behavioral abnormalities and prominent early parkinsonism progressing to a severe dementia. Pathological studies confirmed DLDHF with severe frontal and striatal neuronal loss and gliosis.
Assuntos
Encéfalo/patologia , Demência/complicações , Doença de Parkinson/etiologia , Idade de Início , Demência/patologia , Demência/fisiopatologia , Humanos , Masculino , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologiaRESUMO
INTRODUCTION: Valproic acid is available in two different presentations, Depakine and Depakine Crono. Equivalences in plasmatic levels, efficacy and adverse effects between these two formulations are not fully established. AIM: To compare plasmatic levels, efficacy and plasmatic levels between Depakine and Depakine Crono. PATIENTS AND METHODS: We studied a retrospective series of 238 patients in treatment with Depakine or Depakine Crono and compared plasmatic levels, efficacy and adverse effects between both formulations. RESULTS: A total of 173 patients had taken one formulation and 54 both. Plasmatic levels were similar in both groups. There were more significantly more patients free of seizures among the Depakine Crono group. Significantly better outcomes were seen with Depakine Crono with respect to secondary effects. Adverse effects are significantly less frequent in men than in women. The higher the dose, the higher the incidence of adverse events. CONCLUSIONS: Depakine Crono seems to obtain similar plasmatic levels, is at least as efficacious and is associated with less adverse events that Depakine.
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Anticonvulsivantes/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Epilepsia/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adulto , Anticonvulsivantes/sangue , Anticonvulsivantes/química , Anticonvulsivantes/farmacocinética , Química Farmacêutica , Ensaios Clínicos como Assunto , Preparações de Ação Retardada/química , Preparações de Ação Retardada/metabolismo , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Ácido Valproico/sangue , Ácido Valproico/química , Ácido Valproico/farmacocinéticaRESUMO
We present a retrospective series of the clinical and MRI findings in 16 patients with intramedullary spinal sarcoidosis (ISS), including 12 patients studied with gadolinium-DTPA. The spectrum of MRI findings includes leptomeningeal enhancement, fusiform spinal cord enlargement, focal or diffuse intramedullary disease, and spinal cord atrophy. We present a classification of ISS correlating the clinical progression and the temporal sequence of MRI abnormalities. Improvement occurred in five of 12 patients (42%) treated with immunosuppressive therapy.
Assuntos
Sarcoidose/patologia , Doenças da Medula Espinal/patologia , Adulto , Feminino , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Ácido PentéticoRESUMO
Prevalence figures for inherited neuromuscular disorders are important both for health care planning purposes and for evaluating the need for DNA diagnostic services for eugenic approaches. We screened for the prevalence of myotonic dystrophy (MyD) through extensive inquiry of neurologic and primary health services of Guipúzcoa (Basque Country, northern Spain) between 1989 and 1991. Typical adult-onset and neonatal cases and relatives at risk; suffering from a partial syndrome, were included. In the latter, molecular typing was performed with DNA probes close to the MyD gene to demonstrate the MyD gene carrier status. The high prevalence detected (26.5 cases per 100,000 population) could be explained by methodological factors, but intrinsic factors, such as a possible founder genetic effect or the quick growth of the Guipúzcoa population since the last century may contribute to one of the highest MyD prevalence in the world. In the future, the methodological basis for epidemiologic surveys of MyD must combine molecular technology with more-extensive family inquiries.
Assuntos
Distrofia Miotônica/epidemiologia , Humanos , Distrofia Miotônica/etiologia , Espanha/epidemiologiaRESUMO
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.
Assuntos
Antiparkinsonianos/uso terapêutico , Ergolinas/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Idoso , Cabergolina , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Antidisialosyl antibodies have been previously associated to chronic and acute ataxic neuropathies. We studied the presence of these antibodies in nine patients with acute self-limiting ataxic neuropathy (ASLAN) using ELISA and TLC immunodetection. One patient showed serum IgG immunoreactivity against gangliosides GD3 and GQ1b. The patient's IgG was able to bind to the nodes of Ranvier on frozen human dorsal root. Our studies confirmed that antidisialosyl reactivity is associated to ataxic neuropathy and its specific binding to the dorsal root could explain the predominant sensory involvement. Nevertheless, the low incidence of this reactivity indicates that a different pathogenic mechanism should be involved in most ASLAN patients.
Assuntos
Ataxia/imunologia , Autoanticorpos/sangue , Gangliosídeos/imunologia , Doenças do Sistema Nervoso Periférico/imunologia , Nós Neurofibrosos/imunologia , Raízes Nervosas Espinhais/imunologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Ataxia/sangue , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Gangliosídeos/metabolismo , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imuno-Histoquímica , Incidência , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/sangue , Doenças do Sistema Nervoso Periférico/patologia , Nós Neurofibrosos/metabolismo , Nós Neurofibrosos/patologia , Raízes Nervosas Espinhais/metabolismo , Raízes Nervosas Espinhais/patologiaRESUMO
This multicentre randomised double-blind 3- to 5-year trial was designed to assess whether initial therapy with cabergoline alone or in combination with levodopa prevents or delays the occurrence of long term motor complications in patients with early Parkinson's disease. Patients eligible for study inclusion (n = 412) had early idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 3) and had received no previous treatment with levodopa, selegiline or dopamine agonists. Patients were randomised to receive either cabergoline (0.25 to 4 mg once daily) or levodopa (100 to 600 mg/day) titrated over a maximum period of 24 weeks. Once the optimum or maximum tolerated dose was achieved, it was maintained up to the end-point (development of motor complications confirmed at 2 consecutive 3-month visits) or up to a minimum of 3 years' treatment. Open labelled levodopa was added in both treatment arms when the improvement in motor disability [Unified Parkinson's Disease Rating Scale (UPDRS) factor III] decreased below 30% vs baseline. Both treatments improved motor disability, decreasing UPDRS factor III scores and factor II scores for activities of daily living. The development of motor complications (end-point) was significantly less frequent in patients treated with cabergoline than in levodopa recipients (22% vs 34%; p < 0.02). The relative risk of developing motor complications during treatment with cabergoline was more than 50% lower than with levodopa. Serious adverse events, either drug related or not, were slightly more frequent in cabergoline-treated patients (31%) than in those treated with levodopa (25%). The withdrawal rate in the cabergoline vs levodopa group was 16 vs 13%. In conclusion, the study shows that, in patients with early Parkinson's disease, cabergoline is effective either as monotherapy or combined with levodopa. Moreover, starting treatment with cabergoline significantly delays the development of motor complications.