Biomedical subjects

A M Lozano

Publications and source records attributed to A M Lozano.

At least 19 recordsLinked to original sources

PubMed1998

Phantom sensations generated by thalamic microstimulation.

Many amputees have a sense of their missing 'phantom' limb. Amputation can alter the representation of the body's surface in the cerebral cortex and thalamus, but it is unclear how these changes relate to such phantom sensations. One possibility is that, in amputees who experience phantom sensations, the region of the thalamus that originally represented the missing limb remains functional and can give rise to phantom sensations even when some thalamic 'limb' neurons begin to respond to stimulation of other body regions. Here we use microelectrode recording and microstimulation during functional stereotactic mapping of the ventrocaudal thalamus in amputees to determine both the responses of the neurons to stimulation of the skin and the perceptual effects of electrical activation of these neurons. Thalamic mapping revealed an unusually large thalamic stump representation, consistent with the findings from animal experiments. We also found that thalamic stimulation in amputees with a phantom limb could evoke phantom sensations, including pain, even in regions containing neurons responsive to tactile stimulation of the stump. These findings support the hypothesis that the thalamic representation of the amputated limb remains functional in amputees with phantoms.

Adult↗

PubMed1998

Neuropsychological consequences of posteroventral pallidotomy for the treatment of Parkinson's disease.

OBJECTIVE: Neuropsychological changes were assessed in patients who had idiopathic PD after unilateral posteroventral pallidotomy. METHODS: Posteroventral stereotactic pallidotomies were performed on 42 PD patients (24 right and 18 left hemisphere). All patients were evaluated in the "on state" before the procedure (n = 42) and at intervals of 3 (n = 26), 6 (n = 27), and 12+ (n = 24) months after surgery. RESULTS: Modest improvement in sustained attention and decline in working memory was observed by 6 months after surgery. Left hemisphere lesions led to a loss of verbal learning (-2.2 SD) and verbal fluency (-1.6 SD) in 60% of patients at their first evaluation at 3 or 6 months. No patients returned to baseline on the verbal fluency task and most (71%) did not recover verbal-learning ability by 12 months after surgery. Right hemisphere lesions led to a loss of visuospatial constructional abilities (-3.5 SD), which fully resolved by 12 months for all but one patient. Evidence of further decline of frontal-executive functioning was noted within other tasks but not on a "direct" test (i.e., Conditional Associative Learning). Lastly, behavioral changes of a "frontal nature" were reported in 25% to 30% of patients. These cognitive and emotional costs increased dependence in these domains and negatively affected some patients' relations with caregivers and restricted their ability to function properly at work or in social settings. Caregivers, particularly, and patients who were aware of their resulting changes had difficulty adjusting after surgery. CONCLUSIONS: Although patients and caregivers were generally pleased with the clinical neurologic outcome of the procedure, the neurologic benefits of unilateral pallidotomy must be weighed against modest cognitive and behavioral risks.

Adult↗

PubMed1998

Pallidotomy for Parkinson's disease.

The major motor disturbances in Parkinson's disease are thought to be caused by overactivity of the GABAergic internal segment of the globus pallidus (GPi), which acts as a "brake" on the motor thalamus and the cortical motor system to produce the slowness, rigidity, and poverty of movement characteristic of parkinsonian states. The goal of pallidotomy is to reduce this excessive inhibition on the motor system in patients with Parkinson's disease who continue to be significantly disabled despite pharmacotherapy. GPi can be identified with a high degree of precision through microelectrode recording and stimulation. Micro- and macrostimulation can be used to map the position of the optic tract and the internal capsule, two structures that are at risk with pallidotomy. Although the optimal lesion size and location within the pallidum is yet to be determined, unilateral lesions in the sensorimotor portion of GPi are associated with striking improvements in drug-induced involuntary movements, bradykinesia, tremor, and rigidity and to a lesser extent on gait and postural disturbances.

Globus Pallidus↗

PubMed1998

Pallidotomy and deep brain stimulation of the pallidum and subthalamic nucleus in advanced Parkinson's disease.

There has been a resurgence in the use of neurosurgical procedures for the treatment of Parkinson's disease (PD). Pallidotomy has become a widely performed procedure on the basis of reports which describe marked reduction of levodopa-induced dyskinesias and variable improvement in parkinsonism. Preliminary reports of the effects of globus pallidus internus (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) have also been promising. At 6-month follow up, a cohort of our first 40 patients undergoing pallidotomy demonstrated the following mean improvements when examined after drug withdrawal (off) and under optimal medication (on): total motor off scores-31%; total off activities of daily living scores-30%; and total on dyskinesias-63% (contralateral and ipsilateral dyskinesias improved 82% and 50%, respectively). Although improvements in contralateral dyskinesias and total off parkinsonism were sustained at 2-year follow up (N = 11), benefit for ipsilateral dyskinesias was lost after 1-year follow up (N = 24). and postural stability and gait improvements lasted only 3-6 months. On-period, levodopa-resistant symptoms did not benefit from pallidotomy. Mean improvements in 8 patients undergoing GPi DBS (4 unilateral and 4 bilateral) at 3 months were as follows: total motor off scores-27%; total off activities of daily living scores-26%; and total on dyskinesias-60%. At most recent follow up, 6 patients with STN DBS (5 bilateral and 1 unilateral) showed the following mean improvements: total motor off scores-41%; total motor on scores-27%; total off activities of daily living scores-40%; and total on dyskinesias 41%. Pallidotomy reduces dyskinesias and off disability. GPi DBS may have effects similar to pallidotomy, but might be safer when bilateral procedures are required. Bilateral STN DBS may improve off parkinsonism more than other procedures and might also improve on-period motor function. A randomized trial will be required to determine which procedure is most effective for patients with different clinical features.

Adult↗

PubMed1997

Posteroventral medial pallidotomy in advanced Parkinson's disease.

BACKGROUND: Posteroventral medial pallidotomy sometimes produces striking improvement in patients with advanced Parkinson's disease, but the studies to date have involved small numbers of patients and short-term follow-up. METHODS: Forty patients with Parkinson's disease underwent serial, detailed assessments both after drug withdrawal ("off" period) and while taking their optimal medical regimens ("on" period). All patients were examined preoperatively and 39 were examined at six months; 27 of the patients were also examined at one year, and 11 at two years. RESULTS: The percent improvements at six months were as follows: off-period score for overall motor function, 28 percent (95 percent confidence interval, 19 to 38 percent), with most of the improvement in the contralateral limbs; off-period score for activities of daily living, 29 percent (95 percent confidence interval, 19 to 39 percent); on-period score for contralateral dyskinesias, 82 percent (95 percent confidence interval, 72 to 91 percent); and on-period score for ipsilateral dyskinesias, 44 percent (95 percent confidence interval, 29 to 59 percent). The improvements in dyskinesias and the total scores for off-period parkinsonism, contralateral bradykinesia, and rigidity were sustained in the 11 patients examined at two years. The improvement in ipsilateral dyskinesias was lost after one year, and the improvements in postural stability and gait lasted only three to six months. Approximately half the patients who had been dependent on assistance in activities of daily living in the off period before surgery became independent after surgery. The complications of surgery were generally well tolerated, and there were no significant changes in the use of medication. CONCLUSIONS: In late-stage Parkinson's disease, pallidotomy significantly reduces levodopa-induced dyskinesias and off-period disability. Much of the benefit is sustained at two years, although some improvements, such as those on the ipsilateral side and in axial symptoms, wane within the first year. The on-period symptoms that are resistant to dopaminergic therapy do not respond to pallidotomy.

Activities of Daily Living↗

PubMed1997

Effects of apomorphine on globus pallidus neurons in parkinsonian patients.

Current hypotheses of basal ganglia dysfunction in Parkinson's disease (PD) propose that neuronal hypoactivity in the globus pallidus externus (GPe), and hyperactivity in the output nuclei and the external and internal portions of the globus pallidus internus (GPi,e and GPi,i, respectively), result in the cardinal symptoms of PD. To test this theory, the nonselective D1- and D2-dopamine receptor agonist apomorphine (30-100 microg/kg SC) was administered to 14 levodopa-responsive PD patients who were off medication ("off" state) while recording neurons in GP. For 15 neurons that were continuously monitored, apomorphine was found to increase the firing rate of 3 neurons in GPe, and decrease the rate of 12 in GPi. The mean firing rates of many different neurons were determined before (n = 285) and at various intervals after (n = 184) the injection of the drug. The mean rates before apomorphine were as follows: GPe, 45 Hz (SD 15, n = 85); GPi,e, 67 Hz (SD 14, n = 125); and GPi,i, 85 Hz (SD 19, n = 75). At 25 to 35 minutes after APO, the rate of GPe neurons had increased to 72 Hz (SD 18, n = 7), the rate of GPi,e neurons had decreased to 39 Hz (SD 15, n = 15), and in GPi,i the rate decreased to 34 Hz (SD 22, n = 18). Eighty minutes after apomorphine administration, the mean firing rates returned to preadministration values. This study supports current models of basal ganglia dysfunction in PD and suggests that the therapeutic effect of apomorphine results from a normalization of the imbalance of neuronal activity in the direct and indirect pathways.

Action Potentials↗

PubMed1997

Inhibition of voluntary activity by thalamic stimulation in humans: relevance for the control of tremor.

The motor effects of stimuli delivered through four-channel, quadripolar macroelectrodes chronically implanted in the ventrolateral thalamus were studied in 20 awake cooperating human subjects. Single stimuli could inhibit voluntary contraction of the contralateral first dorsal interosseous muscle (FDI) for up to 200 ms. The inhibition was often followed by a rebound facilitation or by oscillatory activity. This inhibition appeared to arise from the ventrolateral thalamus and could not be obtained in other patients by stimulation of the periventricular grey matter (PVG), the globus pallidus internus (GPI), or the subthalamic nucleus (STN). The neural elements activated by the stimulus had a short chronaxie and a short refractory period, implying that they were large-diameter axons. Similar effects were obtained from each of the four electrodes in the row, suggesting that this fiber system lay parallel rather than perpendicular to the implanted macroelectrode. The inhibition resulting from a single stimulus was diminished by a prior stimulus or train of stimuli. A continuous train of stimuli produced inhibition for only the first 200 ms. We propose that the thalamic stimulus activates a neural network which includes thalamic relay cells and neurons of the thalamic reticular nucleus and that the inhibition of thalamic relay cells habituates with repeated stimuli. It has been suggested that parkinsonian rest tremor results from synchronization of the oscillatory activity of this network. If this is the case, continuous thalamic stimulation might disrupt this oscillation by diminishing the inhibitory phase.

Brain Mapping↗

PubMed1997

Globus pallidus internus pallidotomy for generalized dystonia.

The authors present a young boy with severe generalized dystonia treated with bilateral simultaneous pallidotomy. Microelectrode recordings with the patient under propofol anesthesia showed that the mean discharge rate of globus pallidus internus (GPi) neurons was between 21 and 31 Hz. This contrasts sharply with the mean GPi neuronal firing rates of approximately 80 Hz that are characteristic of Parkinson's disease. The patient had no immediate benefit from surgery, but a progressive improvement in both axial and limb dystonia began within 3 days. The Burke-Fahn-Marsden scores were 75 (maximum possible = 120) at baseline, 52 at 5 days, and 16 at 3 months after surgery. The mechanism of action of pallidotomy for dystonia and the reasons for the delayed and progressive improvement are unknown. Nevertheless, the magnitude of the improvement and the safety of the procedure in this one patient warrant a careful evaluation of pallidotomy for dystonia.

Anesthesia, General↗

PubMed1997

Pallidal and thalamic surgery for Parkinson's disease.

With increasing understanding of the pathophysiology of movement disorders and the refinement of stereotactic techniques, interest in and the scope of surgical techniques for the management of Parkinson's disease have recently rapidly increased. With the option of chronic stimulation or lesion-making in a variety of brain sites, surgical treatment can be increasingly tailored to a particular patient's needs.

Globus Pallidus↗

PubMed1997

The effects of pallidotomy on Parkinson's disease: study design and assessment techniques.

Lesions of the internal segment of the globus pallidus are increasingly being utilized in the surgical treatment of advanced Parkinson's disease, yet studies to demonstrate the safety and efficacy of these procedures are only now being completed. The importance of procedural variations between centres in the outcome of pallidotomy is not yet known. In order to compare accurately results between centres, carefully designed, prospective studies are needed. The authors utilized blinded, randomly evaluated videotaped examinations of pre- and post-operative patients undergoing microelectrode-guided GPi pallidotomy. Their results demonstrate significant effects on contralateral akinesia and tremor in the "off" state, and striking attenuation of levodopa-induced dyskinesias in the "on" state. More modest effects on postural stability and gait disturbance were seen only in non-blinded evaluations. This type of study design should enable many of the outstanding issues related to pallidotomy indications, procedures and outcomes to be addressed.

Adult↗

PubMed1997

Deep brain stimulation and thalamotomy for tremor compared.

Deep brain stimulation (DBS) and thalamotomy are both capable of abolishing tremor. However, no technique is perfect and if thalamotomy proves inadequate so that tremor recurs, presumably because of suboptimal lesion location, the only option is to repeat the thalamotomy. With DBS all that has been necessary to date is to change the parameters of stimulation. Similarly with complications such as the "cerebellar" ones and paraesthesiae. If these occur after thalamotomy one can only wait and hope that they will subside and they do not always do so. With DBS, changing the parameters in the authors' patients has so far been successful in eliminating them. DBS, like thalamotomy is very effective for controlling tremor in Parkinson's disease (PD) and essential tremor (ET) and for improving dexterity in ET, but both techniques are less useful for the control of dopa dyskinesia, Parkinsonian rigidity, or impaired dexterity in PD, though DBS may be better than thalamotomy for the latter condition. On the other hand, both DBS and thalamotomy are very effective in improving dexterity in PD and ET may depend upon the fact that in PD bradykinesia is a major component, whereas in ET only the tremor is. The advantages of DBS over thalamotomy have to be weighed against the peculiar risks of DBS and of course, its cost.

Adult↗

PubMed1997

Identification and characterization of neurons with tremor-frequency activity in human globus pallidus.

Many previous studies have demonstrated the existence of neurons with tremor-frequency activity ("tremor cells") in the thalamus of Parkinson's disease (PD) patients and these neurons are presumed to play a role in the pathogenesis of tremor. Since a major input to motor thalamus (Voa and Vop) is from the internal segment of the globus pallidus (GPi), neurons with tremor-frequency activity in motor thalamus may receive input from neurons in GPi. The aim of this study was to quantify the characteristics of tremor cells in human globus pallidus. In three PD patients with tremor undergoing microelectrode exploration of the globus pallidus prior to pallidotomy, 228 neurons were sampled, and 28 (12.3%) were identified to fire at the same frequency as the tremor. These "tremor cells" were located in the ventral portion of GPi. Autocorrelogram analysis of the sampled spike trains of these 28 tremor cells was carried out over sequential 10-s time segments, and autocorrelograms showing maximal oscillatory activity were graded from 0 to 10. Average tremor cell oscillation grades ranged from 6.8 to 7.8, similar to those reported in the MPTP-induced primate model of parkinsonism. The average tremor cell oscillation grade varied between patients, as did the clinical measures of tremor severity. Tremor cells had oscillations in spike discharges at the same average frequency (4.2-5.2 Hz) as the patient's tremor determined from the electromyogram and accelerometry records of one or more limbs (4.0-5.4 Hz), and the individual values were correlated (r2=0.73) over the total range (3.7-5.6 Hz). The results of this study demonstrate the presence of neurons with 4-6 Hz tremor-frequency activity in GPi, supporting a role of the globus pallidus in the production of rest tremor in PD patients.

Aged↗

PubMed1997

Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms.

Studies of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in monkeys suggest that excessive inhibitory outflow from the internal segment of the globus pallidus (GPi) suppresses the motor thalamus, which reduces activation of the cerebral cortex motor system, resulting in the slowness and poverty of movement of Parkinson's disease (PD). This hypothesis is supported by reports of high rates of spontaneous neuronal discharges and hypermetabolism in GPi (ref. 4-7) and impaired activation of the supplementary motor area (SMA) and dorsolateral prefrontal regions in PD patients. Furthermore, lesion or chronic high-frequency electrical (likely inactivating) stimulation of GPi (ref. 10-14) is associated with marked improvements in akinesia and rigidity, and the impaired activation of SMA is reversed when the akinesia is treated with dopamine agonists. To test whether improvement in motor function with pallidal surgery can be attributed to increased activity in premotor cortical regions, we assessed the changes in regional cerebral blood flow (rCBF) and parkinsonian symptoms during disruption of GPi activity with high-frequency stimulation delivered through implanted brain electrodes. Positron emission tomography (PET) revealed an increase in rCBF in ipsilateral premotor cortical areas during GPi stimulation, which improved rigidity and bradykinesia. These results suggest that disrupting the excessive inhibitory output of the basal ganglia reverses parkinsonism, via a thalamic relay, by activation of brain areas involved in the initiation of movement.

Aged↗

PubMed1997

A brief history of pallidotomy.

A large number of surgical procedures involving the globus pallidus and ansa lenticularis were performed from 1939 to the late 1950s for alleviation of rigidity and tremor, two of the main symptoms of Parkinson's disease. Several groups reported beneficial effects using a wide array of techniques and targets within the pallidum and its projections. Over time, pallidal targets lying in the ventral and posterior portions of the internal pallidum were considered to be the most effective. Based on anatomic studies, surgical misadventures, and empirical observations, there was an abrupt shift regarding the favored target to treat parkinsonian tremor to the thalamus, and most neurosurgeons abandoned pallidotomy in the 1960s. With the advent of L-dopa and the realization of its striking clinical benefits in the mid 1960s, within 5 to 10 years, virtually all surgery for Parkinson's disease ceased. We are now witnessing a rediscovery of pallidotomy as patients with Parkinson's disease are experiencing the shortcomings of medical therapy. In this article, we examine the evolution of pallidotomy and discuss the reasons for the renewed interest in this procedure.

Animals↗

PubMed1996

Stereotactic management of bacterial brain abscesses.

BACKGROUND: CT and MR guided stereotactic techniques have provided promising results in the management of brain abscesses. We reviewed our results of stereotactic management of brain abscesses in 20 consecutive patients with 28 abscesses from 1986 to 1993. METHODS: 13 abscesses were in the cerebral hemispheres, 12 in the cerebellum, 2 in the pons and 1 in the thalamus. The bacterial organism was isolated in 12 of the 20 cases. All patients, except one who had a tuberculous abscess, were on antibiotics for less than 7 weeks. RESULTS: Although there were 3 patients in coma before surgery, the mortality rate was zero and 17 patients had an excellent recovery with 3 patients having a persistent mild neurologic disability. Stereotactic aspiration of the largest lesion in the patients with multiple brain abscesses combined with intravenous antibiotic therapy was sufficient for the resolution of all lesions. Two of our patients treated with antibiotics alone showed abscess progression with neurologic worsening. CONCLUSION: Stereotactic aspiration is safe, accurate, and when combined with the appropriate antibiotics, should be considered the procedure of choice in the management of brain abscesses.

Adult↗

PubMed1995

Effect of GPi pallidotomy on motor function in Parkinson's disease.

The major motor disturbances in Parkinson's disease are thought to be caused by overactivity of the internal segment of the globus pallidus (GPi), in large part due to excessive drive from the subthalamic nucleus. The excessive inhibitory activity of GPi is thought to "brake' the motor thalamus and the cortical motor system to produce the slowness, rigidity, and poverty of movement characteristic of parkinsonian states. To test the hypothesis that direct reduction of Gpi activity can improve motor function, we studied the effect of GPi pallidotomy in 14 patients. The location of the GPi nucleus was confirmed by microelectrode recording before lesion creation. Standardised videotape recordings before and after operation were randomised and scored by a "blinded' evaluator. 6 months after surgery, total motor score in the "off" state had improved by 30% and the total akinesia score by 33%. The gait score in the "off" state improved by 15% and a composite postural instability and gait score by 23%. After surgery there was almost total elimination of drug-induced involuntary movements (dyskinesias), with a 92% reduction on the side contralateral to the pallidotomy. No patient had visual or corticospinal complications. In these patients GPi pallidotomy enhanced motor performance, reduced akinesia, improved gait, and eliminated the neural elements responsible for levodopa-induced dyskinesias.

Activities of Daily Living↗

PubMed1995

Motor effects of stimulating the human cerebellar thalamus.

1. Observations were made on seven human subjects with electrodes implanted in the cerebellar thalamus for the control of tremor. 2. Weak stimulation at 1-2 Hz resulted in sudden lapses of posture of actively contracting contralateral limb muscles. Stronger stimuli caused muscle twitches even in relaxed muscles. 3. The stronger stimuli produced short latency facilitation of EMG activity in contralateral muscles; the pattern of muscle facilitation, the conduction velocity of the descending pathway and the estimated rise time of the underlying composite EPSP were consistent with direct activation of the corticospinal tract. 4. The lapses of posture produced by the weaker stimuli were associated with inhibition of ongoing EMG for up to 150 ms. This was due to the interruption of tonic drive to motoneurons rather than to their inhibition and was associated with depression of the motor evoked potential in relaxed muscles produced by weak anodal transcranial stimulation. The inhibition could be produced by 0.1 ms pulses, implying that a large-diameter fibre system was being activated. 5. A number of mechanisms could contribute to the inhibition, including inhibition from the reticular nucleus of the thalamus.

Adult↗

PubMed1995

An antineuronal monoclonal antibody that reverses neurite growth inhibition by central nervous system myelin.

A component of adult mammalian central nervous system (CNS) myelin causes collapse of neuronal growth cones and inhibits axonal growth, properties that may be responsible for the lack of regrowth of injured axons in the CNS. The molecules and detailed mechanism through which the inhibitory activity acts are not known. To study the cellular molecules mediating the response to this inhibitor, we have used an in vitro neurite growth inhibition assay to screen a panel of monoclonal antibodies raised against rat neuronal membrane proteins, for clones capable of blocking the response. One monoclonal antibody (10D) neutralized the inhibition of neurite growth seen when primary sympathetic neurons, PC12 cells or NG108-15 cells were grown on inhibitory CNS myelin substrates, but did not promote growth on non-inhibitory substrates. 10D reacted with neuronal cells but not myelin substrate proteins. The antigen recognized by 10D appears to play a role in the interaction between neurons and their growth substrates, and is a novel candidate for a cellular receptor or associated signalling molecule mediating the response to myelin inhibitors.

Animals↗