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Biomedical subjects

R A Bakay

Publications and source records attributed to R A Bakay.

At least 37 records · Page 2Linked to original sources

Microelectrode-guided pallidotomy: technical approach and its application in medically intractable Parkinson's disease.

OBJECT: The authors describe the microelectrode recording and stimulation techniques used for localizing the caudal sensorimotor portion of the globus pallidus internus (GPi) and nearby structures (internal capsule and optic tract) in patients undergoing GPi pallidotomy. METHODS: Localization is achieved by developing a topographic map of the abovementioned structures based on the physiological characteristics of neurons in the basal ganglia and the microexcitable properties of the internal capsule and optic tract. The location of the caudal GPi can be determined by "form fitting" the physiological map on relevant planes of a stereotactic atlas. A sensorimotor map can be developed by assessing neuronal responses to passive manipulation or active movement of the limbs and orofacial structures. The internal capsule and optic tract, respectively, can be identified by the presence of stimulation-evoked movement or the patient's report of flashes or speckles of light that occur coincident with stimulation. The optic tract may also be located by identifying the neural response to flashes of light. The anatomical/physiological map is used to guide lesion placement within the sensorimotor portion of the pallidum while sparing nearby structures, for example, the external globus pallidus, nucleus basalis, optic tract, and internal capsule. The lesion location and size predicted by using physiological recording together with thin-slice high-resolution magnetic resonance imaging reconstructions of the lesion were confirmed in one patient on histological studies. CONCLUSIONS: These data provide important information concerning target identification for ablative or deep brain stimulation procedures in idiopathic Parkinson's disease and other movement disorders.

Antiparkinson Agents↗

Deep brain stimulation for movement disorders.

Chronic deep brain stimulation (DBS) is a promising technique for the treatment of movement disorders. Thalamic stimulation is now an established surgical procedure for parkinsonian and essential tremor. Pallidal and subthalamic stimulation are under active investigation as treatments for Parkinson's disease. Although high-frequency DBS at these sites has similar behavioral effects as lesioning, the physiologic mechanisms underlying the beneficial effect of DBS is not well understood and may be extremely complex. DBS offers a potential advantage over ablative therapy because stimulation-induced complications are reversible, and the stimulation parameters are adjustable to minimize complications and maximize therapeutic effects. With this added safety, bilateral stimulation or use of a stimulator following a prior procedure may be preferable to bilateral ablative procedures.

Electric Stimulation Therapy↗

Activity of single action potentials in monkey motor cortex during long-term task learning.

Studies using continuous recording of neural activity during long-term learning are now possible with an implanted neurotrophic electrode. During recording of individual cortical action potentials in monkeys performing a reach and grasp task, we were able to follow the gradual change in firing of several action potentials as the task was learned. Control experiments suggest that the neurons involved in the learning were initially silent.

Action Potentials↗

Stereotactic radiosurgery of malignant and benign intracranial lesions utilizing a patient rotator.

This study examines the characteristics of the patient groups, treatment parameters, and results of therapy for 126 intracranial lesions treated with stereotactic radiosurgery utilizing a "patient rotator" and a linear accelerator. A retrospective review was conducted and data on 122 patients (21 patients with arteriovenous malformations-AVMs, 40 patients with 41 metastatic tumors, 24 patients with malignant gliomas and 37 patients with other benign lesions) were analyzed. Clinical and radiographic response was obtained from chart review and/or telephone follow-up. The average follow-up was 12.1, 13.0, 5.7, and 23.1 months in patients with AVMs, malignant gliomas, metastases, and other lesions, respectively. Median survival times (MST) of the metastatic and glioma group were 9 and 38 months, respectively. Complete or partial radiographic response at follow-up was seen in 62.5% of AVM patients, 33.3% of patients with metastases, 11.8% of patients with malignant gliomas, and 19.3% of patients with other lesions. (1) Local control of brain metastases and benign intracranial lesions can be obtained with single dose stereotactic radiosurgery. (2) The MST and local control rate for metastatic disease obtained are comparable with those in the literature. (3) The patient rotator method for stereotactic radiosurgery is an effective tool for treating selected intracranial lesions.

Adult↗

Effect of stereotaxic intrastriatal cografts of autologous adrenal medulla and peripheral nerve in Parkinson's disease: two-year follow-up study.

Studies in nonhuman primates with experimental parkinsonism have shown that intrastriatal cografts of autologous adrenal medulla and peripheral nerve yield greater behavioral improvement and graft survival than do adrenal medulla grafts alone. To test these observations, five patients with advanced Parkinson's disease were selected to receive unilateral intrastriatal adrenal medulla-intercostal nerve cografts. They were evaluated using the Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol. Three of these patients also underwent quantitative motor testing for the measurement of upper limb bradykinesia (movement time; MT). Following right flank adrenalectomy, cografts consisting of small fragments of adrenal medullary tissue and minced intercostal nerve were stereotaxically implanted into three targets in the right striatum using computerized tomography guidance. Surgery was uneventful and postoperative magnetic resonance imaging revealed accurate placement of the grafts. No morbidity was encountered. Results of 24 months of clinical and quantitative motor assessments postoperatively are reported. Total UPDRS motor scores in the "off" state improved from a mean preoperative score of 39.5 to 32.1 at 3, 29.7 at 6, 27.6 at 9, 28.5 at 12, 31.4 at 18, and 26.5 at 24 months after surgery. Total timed motor test scores during the "off" state improved 17.9% at 6, 23.3% at 9, 18.2% at 12, 38.2% at 18, and 34.9% at 24 months postoperatively compared to baseline. Movement time showed statistically significant improvement (repeated measures ANOVA, P < 0.05) in the left arm (contralateral to surgery) in all three patients tested. These results indicate that stereotaxic intrastriatal implantation of autologous adrenal medulla-peripheral nerve cografts can be performed safely and clinical improvement from this procedure is sustained for a period of 24 months. The clinical improvement was paralleled by improvement in objective, quantitative motor testing.

Adrenal Medulla↗

The role of pallidotomy in Parkinson's disease and dystonia.

Pallidotomy has been re-explored for the treatment of Parkinson's disease and is now being used for the treatment of medically intractable dystonia. Although initial results are favourable for both disorders, determination of the long term benefits will require well controlled clinical trials.

Dystonia↗

Posterior ventral pallidotomy: techniques and theoretical considerations.

1. Microeletrode mapping of the pallidum and adjacent structures allows for precise target identification and localization of critical structures, i.e., optic tract, internal capsule, and external pallidum, which must be spared from lesioning. 2. Microelectrode mapping has provided physiologic-anatomic correlation of determining the optimal target location as related to clinical outcome and has helped to refine the role of stimulation as a tool for target localization. 3. The improved accuracy of this technique should result in more accurate lesion placement which should improve long-term outcome and decrease morbidity.

Brain Mapping↗

A comparison of the patterns of migration and the destinations of homotopically transplanted neonatal subventricular zone cells and heterotopically transplanted telencephalic ventricular zone cells.

The cells arising in the anterior part of the subventricular zone (SVZa) migrate along a well-demarcated pathway which lacks radial glial fibers to the olfactory bulb where they differentiate into interneurons of the granule cell layer or glomerular layer (Luskin, 1993, Neuron 11, 173). To analyze the mechanisms underlying this highly directed migration, we have compared the migratory behavior of unmanipulated SVZa-derived cells to that of homotopically transplanted SVZa cells and of heterotopically transplanted telencephalic ventricular zone (VZ) cells that ordinarily migrate in association with radial glial fibers. To identify the phenotype of the SVZa progenitor cells prior to their transplantation, we characterized them in vitro using cell type-specific markers. After 1 day in culture nearly all the SVZa cells were stained with TuJ1, a neuron-specific marker; only an occasional cell exhibited a glial phenotype as judged by the presence of GFAP-immunoreactivity. This indicates that SVZa cells express a neuronal phenotype. To reveal the spatiotemporal distribution of homotopically transplanted neonatal SVZa cells in a host brain, dissociated SVZa cells from Postnatal Day 0 (P0)-P2 animals were labeled with the lipophilic dye PKH26 or the cell proliferation marker BrdU and implanted into the SVZa of host animals of the same age. Within the first week after transplantation there were vast numbers of labeled cells throughout the pathway. Over the next 2 weeks the labeled cells migrated into the overlying cellular layer of the olfactory bulb and began to differentiate, and within 4 weeks the transplanted cells had reached their final positions in the granule cell and glomerular layers of the olfactory bulb in the same proportions as for unmanipulated SVZa-derived cells. While en route to the olfactory bulb the homotopically transplanted cells never strayed from the migratory pathway. In contrast, heterotopically transplanted VZ cells from the embryonic telencephalon did not undergo migration although they did differentiate. These results demonstrate that the homotopically transplanted SVZa-derived cells adopt a mode of migration indistinguishable from that ordinarily utilized by SVZa-derived neurons and that the VZ cells are unable to decipher the same set of guidance cues.

Animals↗

Treatment of advanced Parkinson's disease by posterior GPi pallidotomy: 1-year results of a pilot study.

The effects of posterior internal pallidal ablation (GPi pallidotomy) on parkinsonian signs and symptoms were studied in 15 patients with medically intractable Parkinson's disease (PD). The sensorimotor territory of the internal portion of the globus pallidus and the adjacent optic tract and internal capsule were identified with microelectrode recording and stimulation. Radiofrequency lesions were then created in the identified sensorimotor territory. Pallidotomy significantly improved all cardinal parkinsonian motor signs (tremor, rigidity, akinesia/bradykinesia, and gait dysfunction) and reduced drug-induced motor fluctuations and dyskinesias. The improvements occurred predominately contralateral to the lesion, but were also present ipsilaterally. Early postoperative (3-month), mean total United Parkinson's Disease Rating Scale scores improved by 30.1% from preoperative values. Mean combined "on/off" Schwab and England Scale scores, a measure of functional independence, increased from 48.8% to 73.0% postoperatively. The mean total United Parkinson's Disease Rating Scale and Schwab and England scores did not show a statistically significant decline over the 1-year postoperative period. Surgery resulted in little morbidity, including a lack of significant deficits on neuropsychological and psychiatric testing. Physical and social functioning and vitality measures on the Medical Outcome Scale also showed significant improvement over the postoperative period. The findings of this pilot study demonstrate that ablation of the sensorimotor portion of the internal pallidum is a highly effective treatment for advanced PD, with benefits sustained at 1 year.

Adult↗

Intracranial adenoid cystic carcinoma: case report and review of the literature.

BACKGROUND: Adenoid cystic carcinoma (cylindroma) is a relatively common head and neck tumor that is slow growing, but locally aggressive and thus prone to recurrence. It is of particular interest to neurosurgeons and neurologists because of its tendency to locally infiltrate neural structures and to spread perineurally. Intracranial involvement has been regarded as rare. METHODS: A case report of a patient with adenoid cystic carcinoma involving the Gasserian ganglion region is presented. The world literature on intracranial involvement of adenoid cystic carcinoma is reviewed. A discussion of the characteristics of this lesion is provided. RESULTS: Our literature review revealed 119 previously reported cases of adenoid cystic carcinoma with intracranial involvement. Our case represents only the tenth reported intracranial case with an unknown primary site. CONCLUSIONS: Although intracranial adenoid cystic carcinoma is regarded as rare, we have accumulated over 100 such reports. A wide variety of primary sites and intracranial sites have been described.

Adult↗

Dopaminergic and GABAergic interneurons of the olfactory bulb are derived from the neonatal subventricular zone.

Earlier studies in our laboratory have demonstrated that a discrete region of the anterior part of the neonatal subventricular zone (SVZa) contains exclusively neuronal progenitor cells. The descendants of the SVZa progenitor cells are destined for the granule cell and glomerular layers of the olfactory bulb, where they differentiate into granule and periglomerular cells, the interneurons of the olfactory bulb, respectively. In the present set of experiments we examined the neurotransmitter phenotype of the SVZa-derived cells. In order to label SVZa-derived cells, the cell proliferation marker bromodeoxyuridine (BrdU) was injected into the SVZa of postnatal day 2 (P2) rats. After 3 weeks, by which time most of the SVZa-derived cells have migrated to their final destination in the bulb, the animals were perfused and their brains processed for immunohistochemistry. To identify the neurotransmitter phenotype of the SVZa-derived cells, sagittal sections of the forebrain, including the olfactory bulb, were double-labeled with an antibody to BrdU in conjunction with an antibody to gamma-amino-butyric acid (GABA) or tyrosine hydroxylase (TH), the rate limiting enzyme in the synthesis of dopamine. Using simultaneous indirect immunofluorescence to detect the presence of single- and double-labeled cells, we found that 59% and 51% of the BrdU-positive cells were immunoreactive for GABA in the granule cell and glomerular layers, respectively. In addition, 10% of the BrdU-positive periglomerular cells were immunoreactive for TH. The presence of double-labeled (BrdU-positive/GABA-positive and BrdU-positive/TH-positive) cells in the olfactory bulb, demonstrates that the SVZa is a source of the GABAergic and dopaminergic interneurons of the olfactory bulb during postnatal development.

Animals↗

Temporal lobe epilepsy and performance on the Wisconsin Card Sorting Test.

The replicability of previous evidence for differential performance between left and right temporal lobe epileptic patients on the Wisconsin Card Sorting Test (WCST) was evaluated in a new sample of candidates for focal resection. Many subjects obtained high scores on indices of perseveration, which are commonly thought to reflect frontal dysfunction, but there were no differences in performance between patients with language-dominant and nondominant temporal foci. The findings confirm existing evidence that performance decrements on the WCST can be associated with epileptic foci and focal lesions in nonfrontal brain lesions.

Adult↗

Electron microscopy of cell islands in layer II of the primate entorhinal cortex.

An electron microscopic analysis of cell islands in layer II of the entorhinal cortex from rhesus monkeys was made to determine the ultrastructural features of these unique neuronal clusters. The rostral, intermediate, and caudal divisions of the entorhinal cortex were selected for electron microscopic examination. In the rostral division, neurons were grouped together in prominent clusters, often with 10 or more contiguous somata. Somatic and dendrosomatic appositions were frequent, without intervening cellular processes or specialized junctions. Somata were relatively small, typically 10-15 microns in diameter, with oval or circular nuclei that were euchromatic and contained nucleoli. Small nuclear infoldings were commonly seen. A thin shell of perikaryal cytoplasm contained numerous organelles. Axosomatic synapses were infrequent, with a mean of only 1.0 synapse per neuron per thin section. The neuropil contained numerous synapses, and myelinated axons were seen infrequently. In the intermediate division, somatic appositions were rarely observed. Somata were relatively large, typically 15-20 microns in diameter, and displayed a moderate amount of cytoplasm. Axosomatic synapses were relatively common, with a mean of 3.3 synapses per neuron per thin section. In the caudal division, neurons were typically grouped in clusters of two to three contiguous somata. Neurons were about 15 microns in diameter and displayed a moderate amount of cytoplasm. Axosomatic synapses were of moderate frequency, with a mean of 2.5 synapses per neuron per thin section. The neuropil in the caudal division displayed a relatively high frequency of myelinated axons. Our analysis of three regions of the entorhinal cortex revealed significant differences in the frequency of somatic appositions and axosomatic synapses, and in certain ultrastructural features of the somata and neuropil. These results showed that cell islands in layer II of the entorhinal cortex display regional morphologic differences. The paucity of symmetric axosomatic synapses in the rostral division may correlate with this region's vulnerability in certain diseases.

Animals↗

Microsurgical revascularization of the ophthalmic artery.

We have developed and performed a microsurgical arterial anastomosis to revascularize the ophthalmic artery in patients with ischemic visual loss, resulting in improvement in visual function. A detailed description of the surgical procedure is discussed as well as the indications for surgery in these cases. An ischemic etiology of visual impairment was predicted by binocular fundus reflectometry, a noninvasive technique to indicate ocular perfusion abnormalities. Encouraging early results suggest that such a revascularization procedure may provide a therapeutic option for a particular group of patients with progressive ischemic visual loss.

Journal Article↗