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Biomedical subjects

M Manrique

Publications and source records attributed to M Manrique.

At least 19 recordsLinked to original sources

Slow oscillatory activity and levodopa-induced dyskinesias in Parkinson's disease.

The pathophysiology of levodopa-induced dyskinesias (LID) in Parkinson's disease is not well understood. We have recorded local field potentials (LFP) from macroelectrodes implanted in the subthalamic nucleus (STN) of 14 patients with Parkinson's disease following surgical treatment with deep brain stimulation. Patients were studied in the 'Off' medication state and in the 'On' motor state after administration of levodopa-carbidopa (po) or apomorphine (sc) that elicited dyskinesias in 11 patients. The logarithm of the power spectrum of the LFP in selected frequency bands (4-10, 11-30 and 60-80 Hz) was compared between the 'Off' and 'On' medication states. A peak in the 11-30 Hz band was recorded in the 'Off' medication state and reduced by 45.2% (P < 0.001) in the 'On' state. The 'On' was also associated with an increment of 77. 6% (P < 0.001) in the 4-10 Hz band in all patients who showed dyskinesias and of 17.8% (P < 0.001) in the 60-80 Hz band in the majority of patients. When dyskinesias were only present in one limb (n = 2), the 4-10 Hz peak was only recorded in the contralateral STN. These findings suggest that the 4-10 Hz oscillation is associated with the expression of LID in Parkinson's disease.

Action Potentials↗

[Analysis of the cochlear implant as a treatment technique for profound hearing loss in pre and postlocutive patients].

INTRODUCTION: These are the objectives planned for this study: 1. Evaluate the results from the communication point of view. 2. Evaluate the cochlear implant (CI) impact on the quality of life. 3. Evaluate medical complications and technical failures. 4. Assess direct and indirect costs generated during the phases of a cochlear implantation programme. 5. Determine which factors have a high impact on the clinical evolution and the financial cost. MATERIALS AND METHOD: A population of 877 patients, postlingual and prelingual, adults and children, have been studied. They were treated in 5 Spanish centres with cochlear implant programmes. Audiometric tests and global questionnaires on life quality have been carried out. Medical and CI technology complications have also been computed. Direct and indirect economic costs of a cochlear implant have been calculated. RESULTS: Postlocutive-implanted patients reached the 40 dB SPL threshold in the Pure Tone Audiometry, and this result was maintained during the 12-year evolution. In Vowels test, it evolved from a 30% on pre-stimulation to 80-90%, in Disyllables words test it evolved from a 10% to a 50-60%, and in CID Sentences test it evolved from an 18% to a 60-70%. In the prelocutive population, results were influenced by the child's age at implantation. The best results were obtained by the children who had been implanted earlier. Those implanted between 0 and 3 years old evolved in the Vowels test from 0% during pre-stimulation to 95%, from a 0% to a 90% in Disyllables words test and from a 0% to a 90-95% in CID Sentences test. Also, the speech acquisition and development of the pre-locutive population was also influenced by the implantation age. An 80% of postlocutive adult patients stated a mood and sociability improvement after the cochlear implantation. They did not show health changes in general nor relevant modifications in the attention they usually received from relatives and friends. Severe medical-surgical complications were registered for a 3.42% of the cases, a 7.06% of mild medical-surgical complications and a 3.07% of technical breakdowns in the internal components of the CI. Financial cost of implantation for a post-locutive adult oscillated between 36,912 Euro and 37,048 Euro, and between 37,689 Euro and 44,273 Euro for a pre-locutive child. CONCLUSIONS: Cochlear implants clearly enhance communication skills of the implantees. Results obtained for the prelocutive implanted population justify the creation of hearing screening programmes in new-borns. Postlocutive implanted adults have expressed satisfaction for the results obtained. However, they did perceive some limitations in situations of unfavourable acoustic conditions. An analysis of direct and indirect costs related to a CI programme has been made. It may be useful to carry out reports on the cost-benefit ratio in this field. The low index of complications observed shows which cochlear implant treatment technique complies with the adequate safety margins. The factors influencing the most in the evolution are: duration of hearing deprivation, age at implantation, cochlear anatomy and functionality of the auditory pathway, patient's and relative's motivation, and the coexistence of other handicaps associated to hearing losses.

Adolescent↗

Advantages of binaural hearing provided through bimodal stimulation via a cochlear implant and a conventional hearing aid: a 6-month comparative study.

CONCLUSIONS: Our study data demonstrate the additional benefit derived from continued use of a contralateral hearing aid (HA) post-cochlear implantation for speech recognition ability in quiet and in noise. Postoperative bimodal stimulation is recommended for all subjects who show some speech recognition ability in the contralateral ear as it may offer binaural listening advantages in various listening situations encountered in everyday life. OBJECTIVES: To assess the benefits derived from bimodal stimulation for experienced HA users implanted with a cochlear implant (CI) (score=20% in disyllabic test). The correlation between pre- and postoperative performance on speech perception measures was examined to determine additional criteria for recommending bimodal stimulation postoperatively. MATERIAL AND METHODS: A within-subject repeated-measures design was used, with each subject acting as their own control. Assessments were carried out preoperatively in aided monaural and best-aided conditions and at 6 months postoperatively in CI-alone, contralateral HA-alone and bimodal listening conditions. Speech recognition using Spanish words and sentences materials was assessed at conversational level and for soft speech in quiet. Speech comprehension in noise was assessed using word materials at a signal:noise ratio of +10, for coincident speech in noise and for spatially separated speech in noise. Twelve adult native Spanish subjects with a severe-to-profound hearing impairment who were experienced with optimally fitted conventional amplification and who displayed suboptimal speech understanding preoperatively were enrolled in the study. Preoperatively, conventional amplification was worn by five subjects binaurally and by seven monaurally. RESULTS: Postoperatively, superior speech recognition ability in quiet and in noise for disyllabic words was achieved using bimodal stimulation in comparison to performance for either monaural aided condition. Mean improvement in speech recognition in the bimodal condition was significant over performance in the CI-alone condition for disyllabic words in quiet at 70 (p=0.006) and 55 dB SPL (p=0.028), for disyllabic words in noise at +10 dB with speech and noise spatially separated with the noise source closest to the contralateral HA (S0NHA) (p=0.0005) and when the noise source was closest to the CI ear (S0NCI) (p=0.002). When testing word recognition in noise with speech and noise sources coincident in space, word scores were superior in the bimodal condition relative to the CI-alone condition but this improvement was not significant (p=0.07). The advantages of bimodal stimulation included significant effects of binaural summation in quiet and significant binaural squelch effects in both the S0NHA and S0NCI test conditions. All subjects showed superior performance in the binaural situation postoperatively relative to the best-aided condition preoperatively for one or more test situations.

Adult↗

Movement-related changes in oscillatory activity in the human subthalamic nucleus: ipsilateral vs. contralateral movements.

A voluntary movement is accompanied by a series of changes in neuronal oscillatory activity in the subthalamic nucleus (STN). These changes can be recorded through electrodes implanted for deep brain stimulation to treat Parkinson's disease in the time interval between the surgery and the internalization of the connections to the batteries. Both baseline activity and movement-related changes are different in the 'on' and 'off' medication motor states. In the 'off' state a low frequency activity in the alpha-beta range (8-25 Hz) that dominates the spectrum is interrupted during the movement, while in the 'on' state baseline frequencies are higher and a peri-movement gamma increase (70-80 Hz) is usually observed. Similar changes have been described with electrocorticographic recordings over the primary motor cortex but the gamma increase was only present during contralateral movements. We compared ipsi- and contralateral movement-related changes in STN activity, using a time-frequency analysis of the recordings obtained simultaneously in both STN and the scalp (electroencephalography) during right and left hand movements. The movement-related changes observed in the STN in the 'on' and the 'off' states were similar to those described previously in terms of predominant frequency bands, but we found bilateral changes in the STN during movements of either hand. A contralateral earlier start of the beta STN changes was mostly observed when the moving hand corresponded to the less-affected side, irrespective of hand dominance. These results suggest that movement-related activity in the STN has, by and large, a bilateral representation and probably reflects cortical input.

Aged↗

[Surgical treatment for Parkinson's disease].

In the past years there has been an increasing interest in the surgical therapies for Parkinson's disease. This renewed interest is related to differents factors. First, pharmacological treatments are still unable to alter substantially the progression of the disease and after a few years they generally cause motor complications and dyskinesias. Secondly, the great advances in the surgical techniques, especially with the improvement of stereotactic surgery, have decreased morbidity in recent years. Finally, the introduction of deep brain stimulation, now allows surgical treatment without damaging brain structures. In this review, different surgical treatments are summarized. Ablative surgery, deep brain stimulation and reinervation therapies are described.

Animals↗

PTEN protein expression correlates with PTEN gene molecular changes but not with VEGF expression in astrocytomas.

PTEN gene (10q23) is a relevant tumor suppressor gene whose protein is a phosphatase involved in the control of angiogenesis of some tumors including astrocytomas. There are no studies correlating molecular changes of PTEN and the immunohistochemical expression of its protein (pPTEN) with the expression of vascular endothelial growth factor (VEGF) in astrocytomas. Fifty-six surgically resected brain gliomas, 10 grade 2, 16 grade 3, and 30 grade 4, were studied by a combined approach, consisting of (1) PCR analysis using four microsatellite markers against the PTEN gene region (10q23), (2) the FISH technique to test chromosome 10 using a pericentromeric probe, and (3) immunohistochemical evaluation of pPTEN and VEGF. Loss of heterozygosity (LOH) of PTEN was observed in 10% of fibrillary grade 2 astrocytomas and all gemistocytic ones. In high-grade tumors, LOH was more frequent in grade 4 than in grade 3 (> or =2 loci deleted, 83% and 56%, respectively). Monosomy for chromosome 10 was observed especially in high-grade tumors (6% of grade 3 and 50% of grade 4) and in 20% of grade 2 tumors, corresponding to gemistocytic astrocytomas. Results with both antibodies against PTEN were concordant: loss of cytoplasmic immunoreactivity was frequently observed according to homogeneous or heterogeneous patterns in 70% and 50% of grades 4 and 3, respectively, but not in grade 2. Immunonegativity of pPTEN was associated with PTEN gene deletion (> or =2 loci deleted) (P = 0.04) but not with monosomy. Cytoplasmic immunoreactivity against VEGF was observed in high-grade and in gemistocytic astrocytomas, but not in conventional grade 2 tumors. Tumor expression of pPTEN was not associated with immunoreactivity against VEGF when the same areas were considered. In conclusion, loss of PTEN expression is frequent in high-grade astrocytomas, but not in grade 2 tumors, and correlates with PTEN deletion and loss of chromosome 10. PTEN immunoreactivity does not correlate with VEGF expression in astrocytomas when similar areas are considered.

Astrocytoma↗

Brainstem auditory evoked potentials (BAEPs) in the cynomolgus macaque monkey. Equivalence with human BAEPs and proposal of a new nomenclature.

Several groups have studied brainstem auditory evoked potentials (BAEPs) in non-human primates. However, the nomenclature of the waves elicited and their correspondence with human waves I-V differ among authors. BAEPs were recorded from six anaesthetised young cynomolgus macaques (Macaca fascicularis), using different sound stimuli parameters. A constant pattern of four main waveforms was present in all the animals with stimulus intensities over 60 dB SPL, although up to four smaller waveforms were observed in some of the individuals. Latency values increased with decreasing stimulus intensities and with increasing repetition rates. These results were similar to the BAEPs observed in other species of macaques. Although an approximate equivalence between human and monkey BAEPs is possible, some discrepancies suggest that there may be generators which contribute to different waves in both species. This is the reason for our proposal of a new nomenclature for BAEP waveforms in monkeys, following a descriptive order with Arabic numerals preceded by the letter M.

Acoustic Stimulation↗

Stereotactic biopsy for brain tumors: is it always necessary?

BACKGROUND: Stereotactic biopsy is currently being used in oncological neurosurgery despite its limitations. The purpose of this study is to compare its diagnostic reliability with that of the diagnosis based on clinical data and neuroimaging techniques. METHODS: We studied 200 patients (134 men and 66 women) who underwent 212 stereotactic biopsy procedures to assess brain tumors. All were subjected to CT scan and 71 patients also underwent MRI. A presumptive diagnosis of brain tumor was established in each case and the findings compared with the results of stereotactic biopsy and the clinical course. RESULTS: A clear presumptive diagnosis was established before stereotactic biopsy in 90% of the patients, and in 95% of this group, the diagnosis was confirmed by the biopsy and/or the clinical course. The stereotactic biopsy modified the presumptive diagnosis in eight patients (4%), without changing the clinical diagnosis of malignant lesion. In our present series, 10% of the procedures were of no help in determining a diagnosis and in 7% of patients, the stereotactic biopsy led to diagnostic errors that influenced the therapeutic management and resulted in an erroneous prognosis. CONCLUSIONS: These data confirm the need for clinical correlation with the findings obtained at stereotactic biopsy and suggest that stereotactic biopsy may not always be useful or necessary in the management of brain tumor patients. According to our present critical analysis, when a clear presumptive diagnosis of brain tumor can be made, it may be sufficient to base the management of the patient only on clinical and neuroimaging findings.

Adult↗

Endoscopic fenestration of a symptomatic cyst of the septum pellucidum.

We present the case of a 25-year-old woman suffering from chronic severe headaches and syncope associated with an expanding cyst of the septum pellucidum. After a simple endoscopic fenestration of the cyst the symptoms resolved, resulting in an excellent clinical outcome. This case shows that simple endoscopic fenestration may produce a rapid and maintained symptomatic improvement in patients with an expanding cyst of the septum pellucidum.

Adult↗

Experimental study following inactive implantation of an auditory brain stem implant in nonhuman primates.

We report changes in the cochlear nuclei (CNs) after 3 months of bilateral auditory deafferentation and simultaneous unilateral implantation of a dummy auditory brain stem implant (ABI) in 6 nonhuman primates (Macaca fascicularis). These specimens were compared to CNs of 9 controls and 7 bilaterally deafferented animals without implantation. The ABI array consists of 3 platinum electrodes mounted on a silicone pad with the back side covered with Dacron. No migration of the ABI was observed. All deafferented animals showed astrocytic reorganization in the CNs. Histologic changes consisted of superficial reactions around the implant, with formation of fibrillar bundles of fusiform cells, and the presence of giant cells close to the Dacron. Other findings were related to surgical trauma. The dummy ABI did not itself provoke serious adverse reactions in the CNs. Our observations support the possibility of ABI reimplantation surgery.

Animals↗

Auditory brainstem implantation in primates: lessons for human surgery and application.

We report on the surgical technique for surface electro-auditory prosthesis (EAP) implantation, pathological changes occurring at the cochlear nucleus complex (CNC), and its relation with electrical stimulation. Fourteen Macaca fascicularis were operated upon for a translabyrinthine bilateral auditory neurectomy, and simultaneous unilateral EAP implantation. Six animals were not stimulated, and the remaining eight were connected to an external active device. Stimulation was planned for 1000 hours. Biotolerance to the materials was adequate without significant reactions in the CNC surface, but an ependymal reaction. Lesions attributed to surgical trauma were also found. Two animals being stimulated could not complete the planned course due to cable break or EAP extrusion. One stimulated animal developed an asymptomatic brainstem abscess. A good knowledge of CNC topography is required to avoid surgical trauma. Externally connected devices may facilitate extrusion of the EAP or ascending infections.

Animals↗

[Surgical treatment of epilepsies: criteria for the selection of patients and results].

INTRODUCTION: Approximately 20% of all epileptic patients are not satisfactorily controlled by the available antiepileptic drugs. Some of these patients have epileptic syndromes which could potentially be treated by surgery. DEVELOPMENT: The technological advances applied to diagnostic and therapeutic methods have improved the identification of epileptic patients who may benefit from surgery. Up to 80% of the patients with focal epilepsies symptomatic of well defined lesions may become free of seizures after excision of the lesion or epileptogenic focus. Other forms of epilepsy, such as the so-called catastrophic infantile forms, may improve temporarily when techniques such as hemispherectomy or callosotomy are used. The morbidity and mortality of these surgical procedures are minimal. The results depend on correct selection of the patients. A strict protocol for rigorous evaluation of the patients should be used, with the collaboration of neurologists, epileptologist neuropaediatricians, neuropsychologists, neurophysiologists, neuroimaging specialists, psychiatrists and neurosurgeons. There should first be clear answers to three key questions: 1. Who is a good candidate? 2. How should the selection be made? and 3. When is the best time for evaluation? CONCLUSIONS: At present it seems clear that the surgery of epilepsy is used less than it could be. It is therefore necessary to encourage the development of specialist units to select patients and treat them, and to develop the means whereby patients can obtain this highly specialized attention.

Brain↗

[Change in metabolic risk factors in obese patients in treatment].

BACKGROUND: Obesity is a threat to health due to its association with cardiovascular risk factors. AIM: To assess the change in metabolic risk factors after weight reduction in obese patients. PATIENTS AND METHODS: A retrospective analysis of 277 obese patients (198 female) aged 39.5 +/- 12 years old, that completed a six month treatment period, consisting in a calorie restricted diet (800-1200 Kcal/day), physical activity, education and group psychological counseling. At the beginning and at the end of the program, weight, waist circumference, resting energy expenditure (REE), serum lipid profile, plasma glucose and plasma insulin levels were measured. RESULTS: During the treatment period, body mass index decreased from 38 +/- 7 to 33.2 +/- 6.4 kg/m2 with a weight loss of 11.7 kg, waist circumference decreased from 106.6 +/- 14.6 to 93.9 +/- 13.5 cm, REE decreased from 1774 +/- 383 to 1585 +/- 267 Kcal/day, blood glucose fell by 5.8%, plasma insulin fell by 40.4%, total cholesterol fell by 7.5%, LDL cholesterol fell by 8.7%, triglycerides fell by 26.6%, and total cholesterol/HDL ratio fell by 12.2%. CONCLUSIONS: Weight loss was associated with improvement in metabolic cardiovascular risk factors in obese patients.

Adolescent↗

Stereological assessment of the glial reaction to chronic deafferentation of the cochlear nuclei in the macaque monkey (Macaca fascicularis).

Neurectomy of the auditory nerve produces a massive deafferentation of the cochlear nuclei (CN) in the brainstem. Degenerating primary afferents are removed in the acute phase, and this is followed by a synaptic reorganization in the CN. As part of an ongoing study on the effect and applicability of auditory brain implants in the CN of Macaca fascicularis monkeys, we studied the chronic response of astrocytes in the CN to bilateral deafferentation of the VIIIth cranial nerve. Four control and five deafferentated animals were employed. The treated animals had a bilateral extradural section of the VIIIth cranial nerve and a survival of 3 months. Animals were euthanized and perfused, and the brainstem was serially sectioned. The astrocyte population of the CN was studied by glial fibrillary acidic protein (GFAP) immunohistochemistry and quantified by unbiased stereological methods. The total length of astrocyte processes, L(proc), was estimated as the product of nuclear volume V(nuc), which was estimated by the Cavalieri method, times the ratio L(V)(proc, nuc) of process length to nuclear volume. Mean nuclear volume was significantly lower in deafferented animals, whereas the mean ratio L(V)(proc, nuc) was higher (albeit no statistical significance was reached). However, the mean total astrocytic process length was virtually the same in both groups. The absence of a length increase in the glial processes indicates a decrease of the astrocytic reaction after the acute phase. No glial scar is present in the CN of the monkey after long-term deafferentation, so the usefulness of auditory brain implants to stimulate CN neurons directly as a means to overcome deafness resulting from direct damage to the VIIIth cranial nerve (i.e., acoustic neuromas) is plausible.

Animals↗

Cerebral auditory plasticity and cochlear implants.

Previous animal research and clinical experiences in humans suggest the existence of an auditory critical period in language acquisition. We review the literature and present the changes within the cochlear nuclei in bilaterally deafferentated adult non-human primates. We also present and analyse the results of 98 prelingually deaf children and teenagers who underwent a cochlear implantation at the University of Navarra. Patients received a Nucleus 22 or 24 multichannel cochlear implant (CI). They were grouped in five categories according to their age at surgery. Performance is compared with a control group of 58 postlinguals. Only early-implanted prelingual children (before 6 years of age) achieved a complete open-set speech recognition, even with better performance than postlinguals. These results clearly demonstrate the existence of a period of high neural auditory plasticity within the first 6 years of life. The introduction of auditory stimulation with a CI can not restore the loss of neural plasticity out of this period. Prelingual children under 6 years of age should receive a CI as soon as there is a reliable diagnosis of bilateral sensorineural hearing loss.

Adolescent↗