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Gurutz Linazasoro

Publications and source records attributed to Gurutz Linazasoro.

At least 19 recordsLinked to original sources
PubMed2006

Electrophysiological characterization of substantia nigra dopaminergic neurons in partially lesioned rats: effects of subthalamotomy and levodopa treatment.

Progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta is the main histopathological characteristic of Parkinson's disease. We studied the electrophysiological characteristics of the spontaneous activity of substantia nigra pars compacta dopaminergic neurons in rats with a partial, unilateral, 6-hydroxydopamine lesion of the nigrostriatal pathway. In addition, the effects of subthalamotomy and prolonged levodopa treatment on the activity of dopaminergic neurons were investigated. As a result of the lesion ( approximately 50% neuronal loss), the number of spontaneously active neurons was significantly reduced. Basal firing rate, burst firing and responsiveness to intravenously administered apomorphine remained unchanged. In contrast, the variation coefficient, a measure of interspike interval regularity, was significantly increased. Ibotenic acid (10 microg) lesion of the ipsilateral subthalamic nucleus in lesioned rats did not modify the electrophysiological parameters. However, prolonged levodopa treatment (100 mg/kg/day + benserazide 25 mg/kg/day, 14 days) reversed the irregularity observed in cells from lesioned rats, while it induced an irregular firing pattern in cells from intact rats. Our results using an experimental model of moderate Parkinson's disease indicate that surviving substantia nigra pars compacta dopaminergic neurons fire irregularly. In this model, subthalamotomy does not modify the firing pattern while levodopa treatment efficiently restores normal firing of SNpc neurons and does not appear to be toxic to them.

Action Potentials↗
PubMed2006

Prevalence of tic disorder in two schools in the Basque country: Results and methodological caveats.

Different studies have shown that the prevalence of tic disorder is highly variable, depending on the methodology employed. The aim of this study was to determine the prevalence of tic disorder among children of two schools. The study was conducted in three successive steps: information to parents and teachers by way of speeches and projection of videotapes; anonymous fulfilling of an ad hoc questionnaire by teachers and parents and identification of children as "possible tic disorder" according to the questionnaire; and confirmation of the presence of tics by direct observation of children at school (20 minutes in each classroom). Eight hundred sixty-seven children were included. Age ranged from 4 to 16 years. Ninety percent of parents and 99% of teachers fulfilled the questionnaire. Seventy-one children had tics according to parents' and 50 according to teachers' opinion (both coincided in 23 cases). Fifty-seven cases were identified after direct observation in the classroom (prevalence of 6.5%). The vast majority of tics were mild in severity and duration. Prevalence obtained in this study was comparable with data reported in studies using a similar methodology, which is higher than results shown in early studies addressed with less rigid methodology. Most of identified cases were quite mild, not leading to major functional disability. In spite of the methodology employed, it is possible that some cases were lost.

Adolescent↗
PubMed2006

Impact of fatigue in Parkinson's disease: the Fatigue Impact Scale for Daily Use (D-FIS).

The Fatigue Impact Scale for Daily Use (D-FIS) was used in a cross-sectional study including 142 consecutive Parkinson's disease (PD) patients. Usual clinical measures for PD, the Montgomery-Asberg Depression Rating Scale and the Parkinson's Disease Questionnaire-8 items were applied. In addition to the D-FIS, patients with fatigue (67.6%, PWF) completed the Multidimensional Fatigue Inventory (MFI), a visual analogue scale for fatigue (VAS-F) and a Global Perception of Fatigue scale (GPF). Relevant psychometric D-FIS results were: floor effect = 4.2%; ceiling effect = 1.1%; skewness = 0.44; item homogeneity = 0.63; Cronbach's alpha = 0.93; item-total correlation = 0.68 (item 1)-0.82 (item 8); standard error of measurement = 2.15; convergent validity with other fatigue measures = 0.54 [GPF]-0.62 [VAS-F] (p<0.001). In a multiple linear regression model, fatigue, depression, and disability independently influenced HRQoL, as measured by the PDQ-8. Patients on amantadine had lower prevalence of fatigue. In PD, D-FIS is a consistent and valid measure for fatigue, a frequent symptom previously found to impair patients' HRQoL. Fatigue was also linked to depression and disability in this study.

Aged↗
PubMed2006

Cell therapy for Parkinson's disease: only young onset patients allowed? Reflections about the results of recent clinical trials with cell therapy and the progression of Parkinson's disease.

The selection of the best candidates for surgery among Parkinson's disease (PD) patients is a debated topic. This could be particularly important for transplantation studies in which patients with advanced PD and motor complications refractory to conventional pharmacological treatments are usually included. The development of lesions in nondopaminergic structures, which apparently are unaffected by the intervention, could eventually lead to the appearance of disabling, treatment-resistant symptoms. This has been considered as the crucial factor responsible for the outcome of any therapeutic procedure. However, other factors might be involved. It is suggested in this article that the rate of progression of PD and the effects of ageing are more important than the extradopaminergic involvement in the final outcome. Rate of progression of PD is critically related to the power of compensatory mechanisms, which are age related and under the control of still unknown genes. Thus, patients with young onset parkinsonism (YOP), either caused by gene mutations or not, could be the best candidates for surgery because they have a slower disease progression and more competent compensatory mechanisms. On the other hand, this can also explain the appearance of unexpected side effects such as the "runaway" dyskinesias reported following transplantation.

Age of Onset↗
PubMed2005

The SCOPA-Motor Scale for assessment of Parkinson's disease is a consistent and valid measure.

OBJECTIVE: The SCOPA-Motor Scale (S-MS) for assessment of Parkinson's disease (PD), contains 21 items in three domains: Motor examination, Disability, and Complications. Our objective was to validate the S-MS Spanish version. STUDY DESIGN AND SETTING: This validation study was based on a multicenter, cross-sectional, one-point-in-time evaluation design. The applied measures were: Unified Parkinson's Disease Rating Scale-3.0 (UPDRS); S-MS; PD Global Evaluation (PDGE); and Clinical Global Impression of severity (CGI). Completeness of data collection, floor and ceiling effect, internal consistency, precision, and construct and discriminative validity were analyzed in 151 PD patients. RESULTS: Scores from S-MS were fully computable. Floor effect was high for Complications (43.7%). Cronbach's alpha was > 0.90 for every domain, and item-total correlation was > 0.70 except for Examination. Standard error of measurement (SEM) ranged from 0.40 to 2.4. Convergent validity with corresponding UPDRS sections yielded coefficients > 0.90. Discriminative validity across Hoehn and Yahr (HY) and CGI stages was significant (Kruskal-Wallis, P < .0001). Insofar as internal consistency was concerned, alpha-values of the Examination sections were marginally higher for the UPDRS than for the S-MS (a finding perhaps accounted for by redundancy in this part of the UPDRS). CONCLUSION: The S-MS is a consistent and valid scale, shorter by almost half than the UPDRS.

Aged↗
PubMed2005

Transcultural comparison of psychogenic movement disorders.

Prompted by the lack of cross-cultural comparative data, and because a better understanding in the different clinical presentations of psychogenic movement disorders (PMDs) is relevant to neurological assessment and interventions, we compared the phenomenology, anatomical distribution, and functional impairment of PMDs in the United States and Spain. Consecutive patients diagnosed with PMD by a movement disorder specialist from one US site and from eight Spanish university centers were included in the study. The two groups were similar in their movement types, anatomical distribution, and functional impairment. PMDs were more prevalent in women than in men and were most common in upper and lower extremities. Gait and speech dysfunctions were distributed similarly in both countries. We found action tremor to be the most frequent PMD in both countries.

Adult↗
PubMed2005

New ideas on the origin of L-dopa-induced dyskinesias: age, genes and neural plasticity.

More than 50% of Parkinson's disease (PD) patients treated with L-dopa develop L-dopa-induced dyskinesias (LIDs) in the long term. Some patients exhibit severe dyskinesias soon after starting low doses of L-dopa, whereas other patients remain free of this disabling complication despite treatment with L-dopa. Avoiding or delaying the appearance of LIDs is one of the main objectives of the management of PD. Plasticity of the brain to adapt to a progressive disease, together with a non-physiological treatment strategy, might be the key physiopathological element that underlies LIDs. Neural plasticity varies among patients according to age and genetics. Thus, I propose that this variation explains the observed differences in the occurrence of LIDs in PD patients. Furthermore, I suggest that denervation and L-dopa treatment act as modulating and triggering factors of LIDs, respectively. In this article, the practical implications of these ideas and the role of pharmacogenetics in PD treatment are discussed. Treatment decisions are likely to rely on this information, challenging the relevance of current 'hot' debates about how to start treatment in PD.

Adult↗
PubMed2004

Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism.

Rapid-onset dystonia-parkinsonism (RDP, DYT12) is a distinctive autosomal-dominant movement disorder with variable expressivity and reduced penetrance characterized by abrupt onset of dystonia, usually accompanied by signs of parkinsonism. The sudden onset of symptoms over hours to a few weeks, often associated with physical or emotional stress, suggests a trigger initiating a nervous system insult resulting in permanent neurologic disability. We report the finding of six missense mutations in the gene for the Na+/K+ -ATPase alpha3 subunit (ATP1A3) in seven unrelated families with RDP. Functional studies and structural analysis of the protein suggest that these mutations impair enzyme activity or stability. This finding implicates the Na+/K+ pump, a crucial protein responsible for the electrochemical gradient across the cell membrane, in dystonia and parkinsonism.

Amino Acid Sequence↗
PubMed2004

Recent failures of new potential symptomatic treatments for Parkinson's disease: causes and solutions.

One major goal of current research in Parkinson's disease (PD) is the discovery of novel agents to improve symptomatic management. The object of these new treatments should be to provide effective symptom control throughout the course of the disease without the development of side effects such as motor and psychiatric complications. Results of several clinical trials of new treatment options reported in the past 2 years have shown negative or unsatisfactory results. Most of the drugs and surgical procedures used in these studies had been tested previously in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys as well as in the classic 6-hydroxydopamine-lesioned rat model. They raise several questions about the true reliability of animal studies, the adequacy of the working hypotheses and design of clinical trials, the validity of tools in current use to evaluate a specific effect, and the selectivity of the drugs used. All these factors may explain failure. This review focuses on pharmacological and surgical treatments tested to improve the management of patients with motor fluctuations and dyskinesias. Some of the recent trials and possible reasons for their lack of success are critically analysed. Finally, some suggestions to avoid further failures and improve results are proposed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2003

Unilateral subthalamic deep brain stimulation in advanced Parkinson's disease.

Eight patients with advanced PD received a unilateral STN DBS. The UPDRS III off drug-on DBS was improved by a mean 44%. Dyskinesias were ameliorated. Levodopa daily dose was reduced. Three patients required the implantation of the second electrode. Unilateral DBS may be efficacious in some patients with advanced PD.

Aged↗
PubMed2002

Levodopa-induced ocular dyskinesias in Parkinson's disease.

Levodopa-induced ocular dyskinesias are very uncommon. Usually they occur simultaneously with limb peak-dose choreatic dyskinesias. We report on a patient with leftward and upward deviations of gaze during the peak effect of levodopa, and hypothesize that a severe dopaminergic denervation in the caudate nucleus is needed for the appearance of these levodopa-induce ocular dyskinesias.

Antiparkinson Agents↗
PubMed2002

Possible sporadic rapid-onset dystonia-parkinsonism.

Rapid-onset dystonia-parkinsonism is a hereditary disease characterized by a combination of dystonic and parkinsonian symptoms. Bulbar musculature is predominantly affected by dystonia. The onset is usually abrupt and the progression of the disease over years is minimal or absent. Homovanillic acid levels in cerebrospinal fluid can be diminished, suggesting that the pathogenesis of the disease is related to some dysfunction in dopaminergic neurotransmission. However, no abnormality has been found in positron emission tomography studies and levodopa does not improve symptoms. The genetic abnormality is not known, but evidence for linkage to markers on chromosome 19q13 has been reported. We describe the case of a woman with a clinical picture highly suggestive of rapid onset dystonia-parkinsonism (RDP) and no family history of the disease.

Adult↗