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Biomedical subjects

G Linazasoro

Publications and source records attributed to G Linazasoro.

At least 19 recordsLinked to original sources
PubMed2004

Pharmacological and PET studies in patient's with Parkinson's disease and a short duration-motor response: implications in the pathophysiology of motor complications.

Patients with Parkinson's disease (PD) and levodopa-induced motor complications experience a short-duration response (SDR) to levodopa which can be considered the basis of motor fluctuations. The SDR is characterized by reduced response duration, increased magnitude of the response and reduced latency to the peak effect. A short latency and a high magnitude are the most salient pharmacological features of the SDR. Its pathophysiology is not totally understood. The pharmacological characteristics of the motor response to apomorphine and their relationship with 6-[(18)F]fluoro-L-dopa (FDOPA) and [(11)C]raclopride (RACLO) uptake were studied in 9 patients with PD. Latency to peak effect was positively correlated with putaminal FDOPA uptake (p<0.05) and negatively correlated with RACLO uptake (P<0.05). A trend towards significance (p:0.06) between magnitude of the response and FDOPA uptake was found which were negatively correlated. Levodopa-induced dyskinesias were negatively correlated with FDOPA uptake (p<0.05) and a trend towards significance (positive correlation) with RACLO uptake was observed (p:0.07). These results suggest that both pre and postsynaptic mechanisms are involved in the origin of the SDR.

Adult↗
PubMed2004

Conversion from dopamine agonists to pramipexole. An open-label trial in 227 patients with advanced Parkinson's disease.

BACKGROUND: Pramipexole is a nonergoline dopamine agonist with D2 and preferential D3 dopamine receptor activity. This selective activity may result in clinically different effects. Small clinical trials indicate that overnight switching from one agonist to another can be performed safely. Objective To determine safety and efficacy of overnight switching from dopamine agonists to pramipexole in patients with advanced Parkinson's disease (PD). OBJECTIVE: To determine safety and efficacy of overnight switching from dopamine agonists to pramipexole in patients with advanced Parkinson's disease (PD). METHODS: Patients with advanced PD and motor complications not optimally controlled by levodopa and a stable dose of bromocriptine, pergolide or ropinirole were converted to pramipexole overnight. Clinical assessments were performed just prior to conversion and after 2, 6 and 12 weeks of treatment, when an optimal dose of pramipexole was achieved. RESULTS: Two hundred and seventeen patients were included in the trial. One hundred and twenty five were converted from pergolide to pramipexole, 58 from bromocriptine and 34 from ropinirole. After 12 weeks, the average dose of pramipexole was 2.8, 2.9 and 3.4 mg/d in patients converted from bromocriptine, pergolide, and ropinirole, respectively. UPDRS II, III and IV scores were reduced by 26-30% in all patients (p<0.0001). Mean levodopa dose was slightly reduced in all groups (p: NS). No serious or unexpected side effects were reported. The dose equivalences calculated from this trial were: bromocriptine:pramipexole 6.9:1, pergolide:pramipexole 0.9:1, ropinirole:pramipexole 1.5:1. CONCLUSION: Switching from bromocriptine, pergolide or ropinirole to pramipexole in an overnight schedule is safe. The observed clinical improvement may be related to a placebo effect, to the use of low doses of dopamine agonists or to a direct effect of pramipexole.

Aged↗
PubMed2003

[Stem cells: solution to the problem of transplants in Parkinson's disease?].

The use of neural transplantation or cellular therapies for Parkinson's disease (PD) is based on the idea of substituting nigral dopaminergic neurons lost as a consequence of the degenerative process. More than 400 people with PD have received a transplant with highly variable results. Success of cellular therapy depends on the survival of a sufficient number of trasplanted dopaminergic cells and on the restoration of normal striatal circuitry, disrupted by the disease process. None of the currently used cellular sources can generate an unlimited number of dopaminergic cells. Stem cells (SC) are pluripotent cells which may be obtained from embryonic, fetal or adult tissues. SC can be isolated, expanded in culture during long periods of time and induced to differentiate into dopaminergic cells. Cellular lines can be created and can be stored. Therefore, a large amount of dopaminergic cells can be obtained from a single SC and they can be used when necessary. Embryonic SC seems to be more plastic than adult SC; however, the plasticity of adult SC may be higher than initially thought due to a phenomenon called transdifferentiation. Several studies carried out in experimental models have shown that SC therapy is viable. SC may be also the ideal vehicle for gene therapy. However, much work remains to be done before SC can be applied to human beings. Different aspects of neural development should be elucidated and important practical problems should be overcome, particularly those related to the development of germinal tumors and immunological rejection. Finally, ethical controversies should be carefully managed. Neurología 2003;18(2):74-100

Adrenal Medulla↗
PubMed2002

Myopathic camptocormia in a patient with levodopa unresponsive parkinsonism.

Camptocormia may be seen in Parkinson's disease. As no changes in paraspinal musculature are found, it is attributed to dystonia or extreme rigidity. However, several cases of parkinsonism and dropped head due to neck extensor myopathy have been reported. We report the first patient with levodopa unresponsive parkinsonism and camptocormia of muscular origin.

Aged↗
PubMed2002

[Discrepancy between imaging and neurophysiology in deep brain stimulation of medial pallidum and subthalamic nucleus in Parkinson's disease].

OBJECTIVE: The objective of this work is to assess the discrepancy in distance between the target chosen by magnetic resonance imaging (MRI) and the final electrode placement after intraoperative microrecording in patients submitted to deep brain stimulation (DBS) for alleviating the Parkinson's disease (PD). METHODS: Thirty patients with PD and motor complications were operated with stereotactic surgery by MRI and microrecording. In 19 patients, the target chosen was the subthalamic nucleus (STN) and in 11 others the target was globus pallidus internus (GPi). In this work it is considered that the electrode has a current field below usual parameters of 1.5 mm radius. Consequently, when the distance error between the final physiological target and the MRI target, is between 1.5 and 3 mm was considered as partial discrepancy and distances of 3 mm or more were considered as total discrepancy. RESULTS: Partial discrepancy for STN and GPi were in 25 and 33% of the cases respectively and total discrepancy was 57 and 42% for each nucleus. The average distance error between both targets, final and image, for X stereotactic coordinate (mediolateral distance) was 1.54 mm for STN and 0.8 mm for GPi. The average distance for Y coordinate (anteroposterior distance) was 2.3 mm for STN and 2.2 mm for GPi. CONCLUSION: There is a significant discrepancy between the final physiological target after microrecording and the target chosen by MRI during surgery for alleviating PD that may induce variations or absence of clinical efficacy in parkinsonian patients submitted to the DBS surgery. Authors suggest the necessity of the microelectrode recording in order to reach the surgical target with the best clinical condition.

Electric Stimulation↗
PubMed2001

[Physiopathology of parkinsonism and dyskinesias: lessons from surgical observations]].

Current models about the organization of the basal ganglia have provided a resurgence of the surgical treatment of Parkinson's disease (PD). Surgical experience has served to corroborate many of the predictions supported by the model. For instance, hyperactivity of the subthalamopallidal pathway is the key feature in PD and its suppression is associated with an improvement of the cardinal signs and symptoms of the disease. Parkinsonian rest tremor may be related to the oscillatory activity of the subthalamic and pallidal neurons. However, some clinical observations can not be entirely explained by the model. The most important paradox is the disappearance of levodopa-induced dyskinesias after pallidal surgery. This review critically analyzes the validity of the current model based on the surgical observations.

Animals↗
PubMed2000

Worsening of Parkinson's disease by citalopram.

More than 50% of the patients with Parkinson's disease (PD) may experience mood disturbances. Serotonin-selective reuptake inhibitors (SSRI) are very active in the management of depression. Citalopram is a new SSRI increasingly used in the treatment of depression. The question of a negative impact of SSRI on the motor function of patients with PD is an important clinical issue. A number of such observations have published with various SSRI, but none, up-to-now with citalopram. We report the case of a patient with PD who experienced a worsening in the motor status soon after the addition of citalopram to her antiparkinsonian drug regime. This single case report suggests that this potential adverse event is a class related side effect.

Journal Article↗
PubMed2000

Excitotoxic ablation.

Explore the source record for details and available documents.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is rapidly becoming the preferred surgical choice for the treatment of advanced Parkinson's disease (PD). We report initial results in 15 patients after 12 months and in nine patients evaluated between 30 and 36 months postoperatively. Our experience confirms the robust antiparkinsonian effect of DBS of the STN in advanced PD. The severity of "off" episodes, as assessed by the Unified Parkinson Disease Rating Scale (UPDRS), was drastically reduced by 74% at 12 months, and dyskinesia scores (Dyskinesia Rating Scale) decreased. The levodopa daily dose was reduced by 55% at 12 months. A double-blind assessment to determine the effect of stimulation performed in nine patients at 3 months in the "off" medication condition was very significant (p<0.05). Nine patients have been followed for 3 years with maintained efficacy in the UPDRS "off" score and the dyskinesia score. The experience of other groups using a similar technique is reviewed. The overall assessment indicates a high antiparkinsonian effect of DBS of the STN even in advanced patients. The existence of a learning curve for this procedure should be taken into account when initial results are evaluated.

Electric Stimulation Therapy↗
PubMed1999

Stereotactic targeting of the globus pallidus internus in Parkinson's disease: imaging versus electrophysiological mapping.

OBJECTIVE: The reintroduction of pallidotomy for the treatment of Parkinson's disease (PD) has generated various opinions regarding the ideal anatomic or physiological location of the target within the globus pallidus. The role of microelectrode recording guidance in pallidotomy for the treatment of advanced PD is presently under debate. The purpose of this study was twofold. The first goal was to determine the degree of accuracy in the targeting of the globus pallidus internus (GPi) with magnetic resonance imaging (MRI), by comparing these results with the final placement of the thermolytic lesions (as defined by electrophysiological assessment). The second goal was to ascertain the somatotopic arrangement of the GPi in PD. METHODS: The analysis involved 50 patients with PD who underwent microrecording-guided pallidotomy. The theoretical coordinates for lesioning were calculated after definition of the intercommissural line by MRI. The actual placement of the lesions was determined after mapping of the GPi by microrecording, using stimulation to identify the sensorimotor region and its somatotopic organization. RESULTS: In most cases, the lesions were placed posterior and lateral to the targets chosen by MRI. Mapping by microrecording revealed differences of 2.3 +/- 1.55 mm and 3 +/- 1.9 mm in the mediolateral and anteroposterior coordinates, respectively. The actual lesion overlapped the theoretical target for only 45% of the patients. The somatotopic organization of the GPi was analyzed. Most of the units with sensorimotor activity or tremor-related activity were in the lateral portion of the nucleus. Upper limb and axial units were in the most lateral region and mainly in the ventral one-third of the nucleus. Lower limb responses were recorded mainly in the dorsal one-third of the nucleus. Tremor-related cells were found throughout the sensorimotor region of the nucleus. CONCLUSION: These results indicate that lesion targeting based on MRI alone is not sufficiently accurate to guarantee placement of the lesion in the sensorimotor region of the GPi.

Adult↗
PubMed1999

[Pallidotomy in the treatment of complicated Parkinson's disease: clinical results at two years and analysis of prognostic factors].

BACKGROUND: There is a renewed interest in pallidotomy as a treatment for complicated Parkinson's disease (PD). AIM: To present the clinical results as well as the analysis of prognostic factors obtained in 28 patients with PD and motor complications submitted to pallidotomy and followed by one year (n = 28) and 2 years (n = 12). RESULTS: The total motor score (Unified Parkinson's Disease Rating Scale [UPDRS]) in the off state improved by 33 and 23% at one and two years, respectively (p < 0.01). All the cardinal signs of the disease were significantly improved (p < 0.01): tremor (92%), rigidity (67%), bradykinesia (46%) and axial symptoms (21%). A slight tendency to worsening in axial symptoms was observed. Dyskinesias disappeared in all but one patient. The Schawb & England Scale in off was improved by 21%. No improvement in the non-operated side was observed. The subgroup of patients with an improvement of less than 30% in the UPDRS was older than the one with larger clinical benefit. The observed tendency to worsening in the total motor score was related mainly to the progression of the symptoms in the non-operated side. Complications were mild and transient. CONCLUSIONS: Pallidotomy is a relatively safe and effective therapeutic option for complicated PD patients. An adequate selection of patients is necessary, since efficacy is partial and limited to one hemibody.

Adult↗
PubMed1999

[Pathophysiological bases, clinical results and indications for surgical treatment in Parkinson disease].

We review the present status of surgery for Parkinson's disease. Surgical options for Parkinson's disease are rapidly spanding. The main objectives of surgical techniques are to restore the dopaminergic deficit in the striatum (transplantation) and to normalize the neuronal activity of the subthalamic-pallidal circuit (pallidotomy and deep brain stimulation). Whereas cell transplantation is still considered an experimental procedure, ablative procedures and deep brain stimulation are widely used. Both types of surgical procedures are supported by strong scientific data. However, much work remains to be done in order to understand several aspects not clearly elucidated at present. The results and current indications for pallidotomy and deep brain stimulation are analyzed.

Brain↗