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Biomedical subjects

A M Lozano

Publications and source records attributed to A M Lozano.

At least 73 records · Page 4Linked to original sources
PubMed1999

Cortical reflex myoclonus studied with cortical electrodes.

OBJECTIVE: To study the mechanism of cortical reflex myoclonus. METHODS: A patient with stimulus sensitive myoclonus of the left foot had an array of subdural electrodes placed over the right sensorimotor cortex. RESULTS: Stimulation through one of the electrodes (contact 13) facilitated leg muscles with the shortest latency and was presumed to lie over the motor cortex. Tibial nerve stimulation evoked a potential with the shortest latency 1 cm further posteriorly (contacts 11-12). These contacts were presumed to lie over the sensory cortex. The potential at 11-12 was followed by a much larger potential that reversed polarity at contact 13. Back averaging from spontaneous myoclonic jerks showed a cortical premovement potential which reversed polarity at contact 13. The threshold for the motor evoked potential in leg muscles evoked by transcranial magnetic stimulation was lower on the affected side. Electrical stimulation through contact 13 produced cortical potentials that could be recorded at adjacent contacts. The combination of a positive potential followed by a negative potential recurred at approximately 35-40 ms intervals, each positive potential generating a myoclonic jerk. Additional waves resembling I waves accompanied only the first positive potential. Surgical removal of the cortex under electrode 13 abolished the myoclonus. CONCLUSIONS: The myoclonic jerks arose in the motor cortex. We postulate that there is increased excitability or synchronization of the cortical neurons at that site. The spontaneous, peripherally induced and recurrent cortical potentials and myoclonic jerks can occur without participation of the circuitry of the presumed I waves.

Aged↗
PubMed1999

New developments in the surgery for Parkinson's disease.

Despite optimization of medical therapy, a large number of patients with Parkinson's disease continue to be disabled. For this group, alternate treatment strategies such as neurosurgical intervention can be considered. Recent advances in neurosurgical techniques and in understanding the pathophysiology of motor disturbances in PD have made surgery safer and more effective. Functional neurosurgical procedures to lesion or electrically modulate dysfunctional basal ganglia circuits or to protect or restore dopaminergic transmission are being increasingly used. These procedures are having a profound impact on the motor disturbances of PD and are producing important improvements in quality of life of patients.

Adrenal Medulla↗
PubMed1999

Neurophysiological effects of stimulation through electrodes in the human subthalamic nucleus.

The effects of stimulation through macroelectrodes implanted in the subthalamic nucleus (STN) were studied in 14 patients with parkinsonism. Single stimuli delivered directly to the STN electrodes with an external stimulator modulated voluntary electromyography (EMG) of contralateral muscles in most patients. A short-latency facilitation ('peak') was attributed to the activation of the corticospinal system. A longer latency inhibition ('dip'), often preceded or followed by facilitations, appeared to arise from the activation of large-diameter fibres running parallel to the electrode and to be transmitted through the motor cortex. It is possible that the dip could result from the inhibition of thalamocortical neurons. With high-frequency stimulation ( approximately 100 Hz) the peaks occurred at the stimulus frequency; the dips became confluent and outlasted the duration of the stimulus train. There was no evidence that high-frequency stimulation produced 'blocking'. The studies were repeated in 12 patients a mean of 5.8 months after implantation of the stimulator. The same short-latency effects were obtained. They were present on 7 out of 23 sides at the settings in use and on the majority of sides if the stimulus intensity was slightly increased. There was no clear relationship between these short-latency effects and the patients' overall clinical improvement; the effects may result from the spread of current to large-fibre systems near the STN. In five patients, high-frequency stimulation on one side immediately reduced tremor in the contralateral limbs. This effect arose from the activation of large-diameter fibres and, like the dip, had about the same threshold at each of the contacts. Frequencies as low as 70 Hz were sufficient. We conclude that the control of tremor by STN stimulation is due to the activation of a large-fibre system.

Adult↗
PubMed1999

Relationship of lesion location to clinical outcome following microelectrode-guided pallidotomy for Parkinson's disease.

The purpose of this study was to examine the relationship between lesion location and clinical outcome following globus pallidus internus (GPi) pallidotomy for advanced Parkinson's disease. Thirty-three patients were prospectively studied with extensive neurological examinations before and at 6 and 12 months following microelectrode-guided pallidotomy. Lesion location was characterized using volumetric MRI. The position of lesions within the posteroventral region of the GPi was measured, from anteromedial to posterolateral along an axis parallel to the internal capsule. To relate lesion position to clinical outcome, hierarchical multiple regression analysis was used. The variance in outcome measures that was related to preoperative scores and lesion volume was first calculated, and then the remaining variance attributable to lesion location was determined. Lesion location along the anteromedial-to-posterolateral axis within the GPi influenced the variance in total score on the Unified Parkinson's Disease Rating Scale in the postoperative 'off' period, and in 'on' period dyskinesia scores. Within the posteroventral GPi, anteromedial lesions were associated with greater improvement in 'off' period contralateral rigidity and 'on' period dyskinesia, whereas more centrally located lesions correlated with better postoperative scores of contralateral akinesia and postural instability/gait disturbance. Improvement in contralateral tremor was weakly related to lesion location, being greater with posterolateral lesions. We conclude that improvement in specific motor signs in Parkinson's disease following pallidotomy is related to lesion position within the posteroventral GPi. These findings are consistent with the known segregated but parallel organization of specific motor circuits in the basal ganglia, and may explain the variability in clinical outcome after pallidotomy and therefore have important therapeutic implications.

Aged↗
PubMed1999

Intraoperative localization of an epileptogenic focus with alfentanil and fentanyl.

UNLABELLED: We evaluated the effectiveness of alfentanil and fentanyl in stimulating epileptogenic activity during surgery for intractable temporal lobe epilepsy under general anesthesia. Ten patients received a standardized anesthetic induction with i.v. fentanyl 5 microg/kg, propofol 3-5 mg/kg, and atracurium 0.5 mg/kg. Maintenance was with isoflurane, 70% N2O/30% O2, and an atracurium infusion. After dural opening, droperidol 0.02 mg/kg was administered i.v.. Both inhaled anesthetics were discontinued and verified to be at 0 end-tidal concentration before the study. Baseline electrocorticography over the surface of the temporal lobe and depth electrode recordings in the amygdala and hippocampus were obtained, followed by 10 min of recording before and after the i.v. administration of both alfentanil 50 microg/kg and fentanyl 10 microg/kg. Any changes in cardiovascular variables were documented. The number of interictal epileptiform spikes at the most active site for each patient was tabulated before and after the administration of each drug. Both alfentanil and fentanyl induced an increase in spike activity in all patients. Alfentanil was more potent, increasing the median number of spikes per epoch from 18 to 58, compared with fentanyl (20 to 42 spikes) (P < 0.05). Alfentanil had a shorter duration of action (4.9+/-1.3 min) compared with fentanyl (8.5+/-2 min) (P < 0.009). In nine patients, the most active site was the hippocampus or amygdala. There was a decrease in mean blood pressure, but only after the administration of alfentanil (P < 0.05). Two patients had electrographic evidence of seizure activity. These opioids can be used to assist in the localization of the epileptogenic focus during surgery. IMPLICATIONS: Both alfentanil and fentanyl activate epileptiform activity in patients with temporal lobe epilepsy. These opioids can be used to assist in the localization of the epileptogenic focus during surgery.

Adult↗
PubMed1999

Variability in lesion location after microelectrode-guided pallidotomy for Parkinson's disease: anatomical, physiological, and technical factors that determine lesion distribution.

OBJECT: To understand the factors that determine the distribution of lesions after microelectrode-guided pallidotomy for Parkinson's disease, the authors quantitatively characterized lesion location in a cohort of patients who were prospectively followed to determine the effects of pallidotomy on clinical outcome. METHODS: Thirty-three patients underwent volumetric magnetic resonance (MR) imaging after surgery to allow quantitative lesion localization in relation to conventional intraventricular landmarks and, alternatively, more anatomically relevant landmarks. The validity of the method was verified in a cohort of postpallidotomy patients who underwent concurrent volumetric and stereotactic MR imaging in an external head frame. Lesions were distributed over a considerable distance in the anteroposterior (8.8 mm) and mediolateral (8.7 mm) dimensions in relation to the anterior commissure and wall of the third ventricle, respectively. Less variation was seen in lesion location in the dorsoventral dimension (4.8 mm) in relation to the intercommissural plane. CONCLUSIONS: Lesion distribution was not random: lesion locations in the anteroposterior and mediolateral dimensions were highly correlated, such that lesions were distributed from anteromedial to posterolateral, parallel to the border of the globus pallidus internus with the obliquely oriented internal capsule. The factors that led to variability in lesion location were variation in third ventricle width and the oblique anteromedial-to-posterolateral course of the internal capsule. This demonstration of variability of lesion location in a cohort of patients who experienced excellent clinical benefits and minimal postoperative complications emphasizes the importance of anatomical variations in determining lesion position and the need for physiological corroboration for correct lesion placement.

Adult↗
PubMed1999

Thalamic stimulation and functional magnetic resonance imaging: localization of cortical and subcortical activation with implanted electrodes. Technical note.

The utility of functional magnetic resonance (fMR) imaging in patients with implanted thalamic electrodes has not yet been determined. The aim of this study was to establish the safety of performing fMR imaging in patients with thalamic deep brain stimulators and to determine the value of fMR imaging in detecting cortical and subcortical activity during stimulation. Functional MR imaging was performed in three patients suffering from chronic pain and two patients with essential tremor. Two of the three patients with pain had undergone electrode implantation in the thalamic sensory ventralis caudalis (Vc) nucleus and the other had undergone electrode implantation in both the Vc and the periventricular gray (PVG) matter. Patients with tremor underwent electrode implantation in the ventralis intermedius (Vim) nucleus. Functional MR imaging was performed during stimulation by using a pulse generator connected to a transcutaneous extension lead. Clinically, Vc stimulation evoked paresthesias in the contralateral body, PVG stimulation evoked a sensation of diffuse internal body warmth, and Vim stimulation caused tremor arrest. Functional images were acquired using a 1.5-tesla MR imaging system. The Vc stimulation at intensities provoking paresthesias resulted in activation of the primary somatosensory cortex (SI). Stimulation at subthreshold intensities failed to activate the SI. Additional stimulation-coupled activation was observed in the thalamus, the secondary somatosensory cortex (SII), and the insula. In contrast, stimulation of the PVG electrode did not evoke paresthesias or activate the SI, but resulted in medial thalamic and cingulate cortex activation. Stimulation in the Vim resulted in thalamic, basal ganglia, and SI activation. An evaluation of the safety of the procedure indicated that significant current could be induced within the electrode if a faulty connecting cable (defective insulation) came in contact with the patient. Simple precautions, such as inspection of wires for fraying and prevention of their contact with the patient, enabled the procedure to be conducted safely. Clinical safety was further corroborated by performing 86 MR studies in patients in whom electrodes had been implanted with no adverse clinical effects. This is the first report of the use of fMR imaging during stimulation with implanted thalamic electrodes. The authors' findings demonstrate that fMR imaging can safely detect the activation of cortical and subcortical neuronal pathways during stimulation and that stimulation does not interfere with imaging. This approach offers great potential for understanding the mechanisms of action of deep brain stimulation and those underlying pain and tremor generation.

Chronic Disease↗
PubMed1998

Parkinson's disease. Second of two parts.

At no time in the past have the basic and clinical sciences applied to Parkinson's disease been so active. Experimental therapies under study at present promise to improve on the limitations of existing treatments. Future progress in understanding the causation and pathogenesis of the disorder will permit the development of new treatments that will slow, halt, or even reverse the currently inexorable progressive course of Parkinson's disease.

Antiparkinson Agents↗
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

Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson's disease.

Microelectrode recording methods for stereotactic localization of the subthalamic nucleus (STN) and surrounding structures are described. These methods accurately define targets for chronic deep brain stimulation in the treatment of Parkinson's disease. Mean firing rates and a burst index were determined for all recorded neurons, and responses to active and passive limb and orofacial movements were tested. STN neurons had a mean firing rate of 37+/-17 Hz (n = 248) and an irregular firing pattern (median burst index, 3.3). Movement-related activity and tremor cells were identified in the STN. Ventral to the STN, substantia nigra pars reticulata neurons had a mean rate of 71+/-23 Hz (n = 56) and a more regular firing pattern (median burst index, 1.7). Short trains (1-2 seconds) of electrical microstimulation of STN could produce tremor arrest but were not found to be useful for localization. Compared with data from normal monkeys our findings suggest that STN neuronal activity is elevated in Parkinson's disease.

Adult↗
PubMed1998

Pallidotomy for tremor.

We studied tremor-related activity in globus pallidus internus (GPi) neurons and the effects of pallidotomy on tremor in patients with Parkinson's disease. By using microelectrode recording, we identified GPi neurons with rhythmic firing at the frequency of contralateral tremor. There was a strong correlation between the tremor-related neuronal activity and limb tremor (r = 0.73). The majority of tremor-related neurons were located in the ventral one half of the caudal GPi, the area that is the target for pallidotomy. We found that pallidotomy produced striking improvements in off-period contralateral tremor. These effects were immediate and were maintained for > or = 2 years. This benefit is obtained despite the progressive nature of the illness and the often reduced dose of medications after surgery.

Globus Pallidus↗
PubMed1998

New developments in understanding the etiology of Parkinson's disease and in its treatment.

Important recent advances have been made in understanding the etiology and pathogenesis of Parkinson's disease, as well as in developing novel treatments. Two newly identified genes, alpha-synuclein and parkin, have been linked to parkinsonism. In addition, disturbances to the normal basal ganglia circuits in Parkinson's patients are being described at both anatomical and physiological levels. These developments provide a strong scientific basis for novel medical and surgical strategies to treat the profound motor disturbances in patients with Parkinson's disease.

Animals↗
PubMed1998

Microelectrode recordings define the ventral posteromedial pallidotomy target.

The benefits of stereotactic ventral posteromedial pallidotomy in the treatment of Parkinson's disease have been recently rediscovered. Optimal lesion location and lesion volume, however, have yet to be determined. Micro-electrode recording and microstimulation are carried out to determine an appropriate site for the placement of electrocoagulation lesions in the medial pallidum. The cellular activity of the globus pallidus is examined for characteristic firing patterns, mean firing rates, movement-evoked activity, and presence of tremor cells, laminae, and border zones. Microstimulation allows the identification of the adjacent optic tract by reports of visual sensation and of the internal capsule by sensorimotor responses. Lesions are centred at sites in the internal segment of the globus pallidus at least 3 mm from these structures, to avoid injury to them during pallidotomy.

Brain Mapping↗
PubMed1998

Brain targets for pain control.

A variety of brain sites have been targeted for surgical treatment of intractable pain. Both ablative and chronic stimulation procedures have been reported to attenuate such pain. These targets include the thalamus and its projections, the periventricular gray, the cingulate cortex and the motor cortex. An overview of these procedures and their efficacy is provided.

Brain↗
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

Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease.

OBJECTIVE: To examine objectively the clinical effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in advanced PD. METHODS: Our initial seven consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic STN DBS underwent a standardized preoperative evaluation followed by a 2-day double-blind evaluation of efficacy 6 to 12 months after electrode implantation. Diaries documenting motor fluctuations and dyskinesias were also completed preoperatively and postoperatively. RESULTS: In the medication-off state, turning the stimulators on resulted in improvement in mean total Unified Parkinson's Disease Rating Scale (UPDRS) motor score by 58% including the following improvements in composite scores: akinesia 57%, rigidity 52%, tremor 82%, and gait and postural stability 49%. Additionally, the medication-off state improved 17% without stimulation, possibly as a result of electrode insertion alone or carry-over of chronic stimulation. In the medication-on, stimulation-on state, all major features of parkinsonism improved and total UPDRS motor score improved 41% compared with before surgery. Activities of daily living were improved while off medication 30%, and levodopa-induced dyskinesias were reduced 83% while total drug dosage was decreased 40%. With chronic stimulation, patients reported that the percentage of time spent in the "on" state (without dyskinesias) increased from 26% to 52% and "off" time decreased from 30% to 6%. Operative complications including cognitive worsening were not uncommon. CONCLUSIONS: STN DBS is a promising new surgical option for the treatment of advanced PD. The marked clinical benefits obtained in these severely disabled patients outweighed the adverse effects.

Aged↗