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J L Molinuevo

Publications and source records attributed to J L Molinuevo.

At least 19 recordsLinked to original sources
PubMed2003

Usefulness of neurophysiologic techniques in stereotactic subthalamic nucleus stimulation for advanced Parkinson's disease.

OBJECTIVE: The objectives of this study are to determine the impact of neurophysiologic guidance on subthalamic nucleus (STN) targeting and to assess its safety and effectiveness. METHODS: We have compared the initial theoretic anatomic target (TAT) of the STN with the final microrecording guided coordinates in 15 consecutive patients with bilaterally implanted electrodes in the STN. The clinical results and adverse effects are also reported. All comparisons were done through a paired Student's t test and Pearson's correlation test. RESULTS: Neurophysiological guidance changed the target coordinates in 26 of the procedures. The mean correction applied to the TAT in order to place the electrode in its definite location was 0.4 mm (+/-0.8, range 0-3; P=0.03) in the medial-lateral axis, 1.6 mm (+/-1.2, range 0-5; P=0.01) in the anterior-posterior plane and 0.8 mm (+/-0.8, range 0-3; P=0.26) in the vertical axis. The mean number of microrecording tracks employed to localize each STN was 2.8+/-1.8 (range 1-8) tracks. After surgery, the total UPDRS motor score in the off medication condition improved by 65.9%; UPDRS-II scores were reduced by 71.8% and Schwab and England scores improved by 45.3%. No intraoperative hemorrhages occurred in this series. CONCLUSIONS: Neurophysiological guidance is a safe and useful tool in order to improve and confirm target localization. The correction applied in the target resulted in a significant clinical improvement 6 months after surgery.

Aged↗
PubMed2003

[Memantine].

Alzheimer's disease (AD) is the most common form of dementia in Western countries. The benefits presently observed with the approved treatments are mainly symptomatic without clear evidence of neuroprotection. N-methyl-D-aspartate (NMDA) receptor antagonists have very extensive therapeutic potential in several central nervous system disorders and can be used as neuroprotective treatment in chronic neurodegenerative diseases and as symptomatic treatment in other neurologic diseases as epilepsy. Memantine, an antagonist of the glutamatergic NMDA receptor, has been recently approved for the treatment of advanced AD. Due to its action mechanism, memantine is considered a neuroprotective drug, whose utility has been demonstrated in preclinical studies, and a useful symptomatic treatment for AD and vascular dementia. We will review both aspects as well as the basic mechanisms mediating glutamatergic neurodegeneration and the implication of glutamate in cognition.

Aged↗
PubMed2000

[Efficacy and safety of posteroventral pallidotomy for the treatment of advanced Parkinson's disease].

OBJECTIVES: To analyze the results, efficacy and safety of unilateral microelectrode guided pallidotomy for the treatment of advanced Parkinson's disease, three months and one year after surgery. PATIENTS AND METHODS: 23 patients with advanced Parkinson's disease (mean age 58.9 years and mean disease duration 14.4 years) were submitted to pallidotomy. Neurological evaluation, three months (n = 23) and one year (n = 16) after surgery, was performed during the morning in overnight "off" condition and after receiving 100-150% of their usual l-dopa dose. Parkinsonian symptoms were evaluated in each follow up visit through motor scales, activities of daily living scales, a dyskinesia rating scale and motor timed tests. RESULTS: Contralateral dyskinesias improved 92% three months after surgery and 89% at one year. Parkinsonian motor scores were reduced by 36.5% after three months and by 26.7% one year after surgery. In the one year follow up visit, contralateral tremor improved 48%, rigidity 36.2% and bradykinesia 37.4%. All these changes were statistically significant (p < 0.01). Adverse effects were minor or transient. Antiparkinsonian medication dosage did not significantly change during the study period. CONCLUSION: Microelectrode guided unilateral pallidotomy is an effective and safe procedure to improve contralateral motor symptoms in Parkinson's disease, being specially useful for the treatment of l-dopa induced dyskinesias.

Aged↗
PubMed2000

Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease.

CONTEXT: Subthalamic nucleus (STN) stimulation may be effective in ameliorating parkinsonian symptoms even to the extent to permit levodopa withdrawal. OBJECTIVES: To analyze the efficacy of STN stimulation in patients with Parkinson disease (PD) and to determine if levodopa may be withdrawn after surgery. DESIGN: Before-after trial. SETTING: Referral center, hospitalized care. PATIENTS: Fifteen patients with advanced PD. INTERVENTIONS: Microelectrode-guided bilateral STN high-frequency stimulation. OUTCOME MEASURES: Before surgery patients were evaluated in off-medication and on-medication conditions. Dopaminergic drug dosages were reduced after surgery, aiming for complete withdrawal. Six months after surgery, patients were reeavaluated in off- and on-medication conditions, with the stimulation turned on and off. RESULTS: Total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the off-medication condition improved by 65.9%; and axial symptoms, bradykinesia, rigidity, and tremor improved by 65.8%, 60.4%, 66.1%, and 81.1%, respectively. UPDRS part II scores were reduced by 71.8% and Schwab and England scores improved by 45.3%. Levodopa was withdrawn in 8 patients and the overall levodopa dose was reduced 80.4%. "Off" time was reduced 89.7% and the severity of dyskinesias decreased 80.6% after surgery. All results reached significance (P<.001). Stimulation of the STN achieved antiparkinsonian effect similar to that of treatment with levodopa. No life-threatening adverse effects occurred. CONCLUSIONS: Bilateral STN stimulation safely improves all parkinsonian symptoms, decreases or eliminates the need for levodopa, and ameliorates motor fluctuations and dyskinesias. Complete withdrawal of levodopa is feasible with this technique and the overall motor effect of STN stimulation is quantitatively comparable to that obtained with levodopa.

Aged↗
PubMed2000

Pallidotomy and quality of life in patients with Parkinson's disease: an early study.

The purpose of this study was to analyze the effect of stereotactic neurophysiologically guided pallidotomy on health-related quality of life (QoL) of patients with Parkinson's disease (PD). Eleven patients with PD (seven men, four women; mean age, 57.2 years; mean duration of disease, 14 years) with motor complications refractory to medical therapy underwent unilateral pallidotomy. Clinical assessment was carried out a week before surgery and 4 months after the surgical procedure and was based on the Core Assessment Program for Intracerebral Transplantations protocol. QoL was measured by means of the PDQ-39. A set of rating scales (Hoehn & Yahr, Unified Parkinson's Disease Rating Scale, Schwab and England, Northwestern University Disability Scale of Walking, Abnormal Involuntary Movement Scale), timed tests, and self-evaluations of motor function and mood were applied. Improvement was found in dyskinesias (74%) and off-period disability (42%). Cardinal motor signs improved significantly (30%-59%). Four dimensions of the PDQ-39 (Mobility, ADL, Emotions, Bodily Pain) showed a significant improvement (p <0.01-0.001). The global effect on QoL, measured through the PDQ-39 Summary Index (35.3%; 95% confidence interval: 15.60-54.97), was also significant (p<0.01) but unrelated to major clinical changes. Pallidotomy significantly improves QoL in patients with advanced PD. QoL measurement provides relevant information that is probably not attainable by clinical assessment.

Aged↗
PubMed2000

Progressive supranuclear palsy: earlier age of onset in patients with the tau protein A0/A0 genotype.

Genetic studies have detected an association between the presence of the tau gene A0 allele and patients with progressive supranuclear palsy (PSP). This study examined whether patients with this polymorphism exhibit distinct demographic or clinical characteristics. We studied 26 patients who fulfilled clinical criteria for the diagnosis of PSP, 20 who had the A0/A0 genotype and 6 who had other genotypes. A questionnaire on demographic data, past medical history, familial history, and initial symptoms was completed as part of the consultation. A complete neurological examination was performed and PSP symptoms were quantified following Golbe's PSP disability scale. We found a significant difference in the age at onset of PSP symptoms, which was 65.9 +/- 5.3 years in the A0/A0 group and 71.2 +/- 5.6 in the non-A0/A0 group (P = 0.016). There were no significant differences in the years from disease onset between the two groups. Symptom severity did not differ significantly in patients with the different A0/A0 genotypes. The detection of significantly lower age at onset with the A0/A0 alleles is consistent with the known association of this genotype as a risk factor for PSP. No significant differences were detected in symptom severity between the two groups of patients.

Age of Onset↗
PubMed2000

The effect of transcranial magnetic stimulation on reaction time in progressive supranuclear palsy.

OBJECTIVE: Reaction time is shortened when a startling acoustic stimulus (SAS) is delivered together with the 'go' signal in normal subjects and patients with Parkinson's disease (IPD), but not in patients with progressive supranuclear palsy (PSP). Similar shortening of reaction time has been reported in normal subjects and patients with IPD with transcranial magnetic stimulation (TMS). In this paper, we analyzed the effect of TMS on reaction time in patients with PSP. METHODS: Six patients with PSP received the instruction to extend the wrist to a visual cue. In test trials, the visual signal was accompanied by either a SAS or a subthreshold TMS applied to the motor area. The same experimental paradigm was applied to 7 patients with IPD, and 10 normal subjects. We measured both reaction time and the slope of the initial accelerometric displacement (SAD). RESULTS: Neither TMS nor SAS changed significantly reaction time in PSP patients. This observation was in contrast with the marked reaction time shortening induced by both stimuli in a similar amount in normal subjects and patients with IPD. Furthermore, SAS and TMS did not modify the SAD in PSP, but shortened it significantly in IPD. CONCLUSION: The absence of an effect of TMS and SAS on reaction time in PSP patients suggests that these patients have a dysfunction in the mechanisms of facilitation of reaction time. The fact that TMS and SAS induced similar effects on reaction time in normal subjects, IPD and PSP patients indicate the possibility of common mechanisms of action for both types of stimuli.

Brain↗
PubMed1999

Identification of a novel polymorphism in the promoter region of the tau gene highly associated to progressive supranuclear palsy in humans.

An intronic polymorphism and other changes in the transcribed region of the tau gene forming a haplotype have been previously described associated to progressive supranuclear palsy (PSP). These results raised the possibility that a change at or near the tau gene could be responsible for an increased risk to develop PSP. We initiated the present work in research for potential changes in the promoter region of the tau gene that could further extend the previously described haplotype. The tau promoter region was analyzed through single strand conformation polymorphism followed by direct sequencing in PSP patients (n = 35), in controls (n = 195) and in Alzheimer's disease (AD; n = 74) patients. We have been able to identify a G to C change at position -221 of the tau gene promoter region. The CC genotype has been detected to be present with a significantly higher frequency in PSP patients (91.4%; P < 0.00001; OR = 11.8), but not in AD patients, as compared with controls (49.74%). Subsequently we have detected that the CC -221 tau promoter genotype is significantly associated to the tau intronic A0/A0 genotype (P < 0.00001). The detected -221 tau G to C change occurs within a potential c-myb proto-oncogene element present in the promoter region. Thus, in addition to extending the previously described haplotype associated to PSP, this -221 G to C change is an interesting candidate that could provide a potential explanation for the association of the haplotype to increased risk for developing PSP.

Base Sequence↗
PubMed1999

Clinical outcome of patients with anti-Hu-associated encephalomyelitis after treatment of the tumor.

OBJECTIVE: To evaluate 1) the effect of the tumor treatment on the clinical course of paraneoplastic encephalomyelitis (PEM) with anti-Hu antibodies, 2) the impact of immunotherapy on the tumor evolution, and 3) the outcome of the small cell lung cancer (SCLC) of PEM patients compared with that of patients without PEM. METHODS: The authors retrospectively analyzed 51 PEM patients (42 with SCLC, 9 with other tumors) who received antineoplastic treatment with (25 patients) or without (26) concomitant immunotherapy. Tumor response was assessed at the end of the antineoplastic treatment. Progression of PEM was defined as a change of at least 1 point in the Rankin scale measured at the onset and at the end of the tumor treatment. To evaluate the outcome of SCLC, 27 PEM patients with SCLC were matched one-to-one with SCLC patients without PEM for age, performance status, tumor stage, and type of antineoplastic treatment. RESULTS: Thirty-six (70%) patients were neurologically stable at the end of the tumor treatment. In a logistic regression analysis, tumor complete response was the only predictor of PEM stabilization (OR 7.07; 95% CI 1.68 to 29.76; p = 0.006). Immunotherapy did not modify the outcome of the tumor and PEM. Median survival was similar in SCLC patients with and without PEM, but the probability of survival at 30 months was higher in PEM patients with SCLC (OR 5.26; 95% CI 1.0004 to 27.6902; p = 0.03). CONCLUSIONS: Complete response of the tumor seems to have a favorable influence on the course of paraneoplastic encephalomyelitis (PEM). Concomitant immunotherapy does not adversely affect the tumor outcome. The small cell lung cancer of PEM patients may have a slightly better evolution than that of patients without PEM.

Adult↗
PubMed1999

Central motor conduction time in patients with multifocal motor conduction block.

The finding of conduction block (CB) within short consecutive segments along a motor nerve is a key feature of multifocal motor neuropathy (MMN). Despite their different pathogenesis, this may be the only clinical difference between some cases of MMN and the pure spinal muscular atrophy form of motor neuron disease (MND). In 12 patients with distal atrophy and fasciculations and electrophysiological evidence of CBs in the upper limbs, we measured the peripheral and central motor conduction times (PMCT and CMCT) to hand muscles. We reasoned that patients with MMN should show an abnormally prolonged PMCT with normal CMCT, whereas an increased CMCT would suggest MND. All patients had delayed F-wave latency and increased PMCT. Three patients had increased CMCT. Follow-up showed little clinical and electrophysiological change in 7 of the 9 patients with normal CMCT, and a progressive motor deficit leading ultimately to death in 1 of the 3 patients with increased CMCT. This patient's electrophysiological follow-up showed a significant decrement of the compound motor action potential to both proximal and distal stimulation points, with disappearance of earlier CBs. Autopsy revealed loss of anterior horn cells and axons of the ventral root, and degeneration of large myelinated fibers. We conclude that determining the CMCT may help in differentiating MND from MMN. Persistence of a stable clinical picture over a span of at least 1 year and lack of electrophysiological signs of involvement of upper motor neurons should both be required before establishing the diagnosis of MMN even with electrophysiological evidence of CB.

Adult↗
PubMed1999

Prepulse modulation of the startle reaction and the blink reflex in normal human subjects.

Blink reflexes are usually considered the most representative and consistent response of the auditory startle reaction (ASR), and they are often the only response evaluated in human psychophysiological studies. However, auditory stimuli also induce an auditory blink reflex (ABR), the physiological characteristics and brainstem circuitry of which may be different from those of the ASR. This study aimed to investigate whether there were differences between the orbicularis oculi (OOc) responses elicited with the ABR (OOcABR) and those elicited with the ASR (OOcASR) regarding their behavior to prepulse modulation. For comparison, we also examined the OOc responses to supraorbital nerve stimulation (OOcEBR). Electromyographic responses were simultaneously recorded from the OOc, masseter (MAS) and sternocleidomastoid (SCM) muscles. ABRs were considered when auditory stimuli induced responses limited to the OOc, and ASRs were considered when responses were induced in all muscles recorded from. Prepulse stimuli were either a weak electrical stimulation at the third finger (somatosensory prepulse) or a weak acoustic tone (auditory prepulse) that preceded the response-eliciting stimuli by intervals ranging from 0 to 200 ms. Prepulse effects differed according to prepulse modality, but the OOcABR and the OOcASR were always modulated in the same way. In both responses, somatosensory prepulses induced facilitation from 20 to 50 ms, followed by inhibition beyond 75 ms, and auditory prepulses induced no facilitation but a significant inhibition beyond 30 ms. In the OOcEBR, both somatosensory and acoustic prepulses induced facilitation of R1 and inhibition of R2 beyond 30 ms. Our results suggest that the OOcABR and the OOcASR exhibit the same physiological behavior regarding prepulse modulation. It is hypothesized that prepulse facilitation is due to direct impingement of subthreshold excitatory inputs onto the facial motoneurons while prepulse inhibition results from the engagement of a presynaptic inhibitory circuit in the brainstem.

Acoustic Stimulation↗
PubMed1999

Contribution of neurophysiological guidance to stereotactic posteroventral pallidotomy for Parkinson's disease.

The usefulness of microrecording guidance to adequately place pallidotomy lesions is not thoroughly accepted. We have analysed in 23 consecutive Parkinsonian patients the deviation of the first recording track (FRT), which was directed to the theoretical stereotactic target, from the sensorimotor area of the internal pallidum, the internal capsule and the center of the lesion. Standard stereotactic co-ordinates were calculated applying a digitized brain atlas adapted to neuro-imaging techniques. The first recording track (FRT) was located out of the sensorimotor area of the pallidum in 13 cases and out of the internal pallidum in 11 cases. In four of these cases the FRT was within the fibers of the internal capsule. The FRT was displaced posteriorly in 9 patients, anteriorly in 11, medially in 9 and laterally in 9. The mean deviation was 1.8 mm (+/- 1.5) in the medial-lateral axis, and 2.5 mm (+/- 1.9) in the antero-posterior plane. In none of the patients the center of the lesion was co-incident with the theoretical anatomical target. The center of the lesion presented a mean deviation from the theoretical anatomical target of 1,4 mm (+/- 1,1) in the medial-lateral, plane, and 2.5 mm (+/- 1.3) in the antero-posterior plane. In addition, 8 patients presented a deviation from the theoretical anatomical target of more than 3 mm in the antero-posterior plane (mean 4.2+/-0.7 mm) and 4 patients presented deviation in the medial-lateral plane of more than 3 mm (mean 3,4+/-0,2 mm). Lesion location was checked by magnetic resonance imaging. All patients improved to a similar extent to that previously reported by the other groups performing pallidotomy under neurophysiological guidance. At 3 months follow-up, pallidotomy ameliorated contralateral bradykinesia in the off condition by 41%, rigidity by 38%, tremor by 52% and dyskinesias by 92%. No major side effects were noted. We conclude that microrecording guidance is a useful tool for avoiding damage to adjacent structures and to precisely localize the sensorimotor area of the internal pallidum in order to obtain optimal clinical results.

Adult↗
PubMed1999

[New pharmacologic strategies for the treatment of Parkinson disease].

The dopamine precursor, levodopa, and the synthetic dopamine agonists are drugs widely used to alleviate the motor symptoms of idiopathic Parkinson's disease. Recently, several molecules which act on different pharmacological receptors implied in Parkinson's disease pathophysiology, have been developed to be applied as a treatment for its motor and cognitive symptoms. This paper discusses these novel therapeutical strategies, their mechanism of action, and their potential applications. To facilitate its lecture, the article has been structured in several sections. In the first section, drugs acting on dopamine metabolism are described, in the next part recent studies on new dopamine agonists and drugs acting on non-dopamine neuronal receptors are analysed, and finally the role of trophic factors for the treatment of Parkinson's disease is discussed.

Antiparkinson Agents↗
PubMed1998

Significant changes in the tau A0 and A3 alleles in progressive supranuclear palsy and improved genotyping by silver detection.

BACKGROUND: Progressive supranuclear palsy (PSP) is characterized by intraneuronal inclusions of neurofibrillary tangles formed by aggregated tau protein. A significant association between the tau gene A0/A0 genotype and PSP recently has been reported. OBJECTIVES: To determine if a significant association between the tau gene A0/A0 genotype and PSP could be found in an independent population with a genetic background different from that in which the initial association was reported, and to standardize a nonradioactive method for tau gene genotyping. SETTING: Hospital and university research laboratories. SUBJECTS AND METHODS: To facilitate genotyping of the tau gene, we standardized the conditions for silver-based detection of the tau gene dinucleotide polymorphism. Thirty patients from Spain clinically diagnosed as having probable PSP were included in the study and compared with different control groups. RESULTS: A highly significant overrepresentation of the A0/A0 genotype (P<.001) and a decrease in the frequency of the A0/A3 genotype were found in the Spanish patients with PSP compared with the control group. A method based on silver detection was standardized for the genotyping of the tau gene. CONCLUSIONS: The detection of a significant association between the tau gene A0/A0 genotype and PSP in 2 independent populations rules out genetic stratification as an explanation for the association and indicates that the presence of the tau A0/A0 genotype is a risk factor for developing PSP independent of genetic background. Alternatively, the results could be interpreted as a protective effect of the A3 allele.

Aged↗
PubMed1998

Utility of anti-Hu antibodies in the diagnosis of paraneoplastic sensory neuropathy.

Anti-Hu antibodies (Hu-Abs) were positive in 40 patients with paraneoplastic sensory neuropathy (PSN) and in 1 patient with idiopathic sensory neuropathy in a series of 126 patients who presented with clinical features suggestive of PSN. The specificity of Hu-Abs was 99% and the sensitivity was 82%. Nine (18%) PSN patients were Hu-Ab-negative, and their sera did not harbor other specific anti-neuronal or anti-ganglioside antibodies. Small cell lung carcinoma (SCLC) was the leading neoplasm in the Hu-Ab-positive (79%) and Hu-Ab-negative (44%) groups. This study confirms the value of Hu-Abs for the diagnosis of PSN and SCLC and also emphasizes that in patients with possible PSN, the absence of Hu-Abs does not exclude cancer, particularly in those patients with risk factors for SCLC.

Adult↗
PubMed1998

Ictal smile.

PURPOSE: Smiling is sometimes manifested during partial seizures. Its value for localizing the epileptogenic focus is not known. We analyzed smiling as an ictal manifestation possibly useful for seizure localization. METHODS: We reviewed patients referred to the video-EEG monitoring unit who presented a smile as part of their critical symptoms. Ictal smile was defined as an accordant expression accompanied by other characteristic epileptic symptoms and ictal EEG activity. RESULTS: Five of 86 patients experienced partial seizures with an ictal smile. We observed smiling during parietal (two patients) and temporal lobe (three patients) seizures. The right hemisphere appeared to be involved with greater frequency. CONCLUSIONS: Ictal smile is an uncommon manifestation of partial seizures involving temporal or parietal lobes, localized mainly on the right hemisphere.

Adult↗