Reversal of experimental parkinsonism by using selective chemical ablation of the medial globus pallidus

1999 ◽  
Vol 90 (5) ◽  
pp. 928-934 ◽  
Author(s):  
Daniel M. Lieberman ◽  
Marc-Etienne Corthesy ◽  
Alex Cummins ◽  
Edward H. Oldfield
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Kainic Acid ◽  
Globus Pallidus ◽  
Optic Tract ◽  
High Flow ◽  
Content Type ◽  
Chemical Ablation ◽  
Selective Chemical ◽  
Fine Print

Object. Symptoms from Parkinson's disease improve after surgical ablation of the medial globus pallidus (GPm). Although, in theory, selective chemical ablation of neurons in the GPm could preserve vital structures jeopardized by surgery, the potential of this approach is limited when using traditional techniques of drug delivery. The authors examined the feasibility of convection-enhanced distribution of a neurotoxin by high-flow microinfusion to ablate the neurons of the GPm selectively and reverse experimental Parkinson's disease (akinesia, tremor, and rigidity).Methods. Initially, to test the feasibility of this approach, the GPms of two naive rhesus macaques were infused with kainic acid or ibotenic acid through two cannulas that had been placed using the magnetic resonance imaging—guided stereotactic technique. Two weeks later the animals were killed and their brains were examined histologically to determine the presence of neurons in the GPm and the integrity of the optic tract and the internal capsule. To examine the therapeutic potential of this paradigm, unilateral experimental Parkinson's disease was induced in six macaques by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and their behavior was studied for 12 weeks after chemopallidotomy was performed using kainic acid (three animals) or control infusion (three animals).Conclusions. Chemopallidotomy using kainic acid permanently reversed the stigmata of MPTP-induced parkinsonism. By contrast, the control animals exhibited a transient recovery following intrapallidal infusion and then relapsed back to their baseline state. The use of high-flow microinfusion of selectively active toxins has the potential for treatment of Parkinson's disease and, by expanding the range of approachable targets to include large nuclei, for broad applications in clinical and experimental neuroscience.

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

1998 ◽  
Vol 88 (6) ◽  
pp. 1027-1043 ◽  
Author(s):  
Jerrold L. Vitek ◽  
Roy A. E. Bakay ◽  
Takao Hashimoto ◽  
Yoshiki Kaneoke ◽  
Klaus Mewes ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Globus Pallidus ◽  
Optic Tract ◽  
Internal Capsule ◽  
Nucleus Basalis ◽  
Active Movement ◽  
Topographic Map ◽  
Content Type ◽  
Fine Print

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.

High-frequency stimulation of the globus pallidus internalis in Parkinson's disease: a study of seven cases

1997 ◽  
Vol 87 (4) ◽  
pp. 491-498 ◽  
Author(s):  
Christian Gross ◽  
Alain Rougier ◽  
Dominique Guehl ◽  
Thomas Boraud ◽  
Jean Julien ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Globus Pallidus ◽  
High Frequency ◽  
Rating Scale ◽  
High Frequency Stimulation ◽  
Primary Therapy ◽  
Content Type ◽  
Frequency Stimulation ◽  
Fine Print

✓ The effectiveness of ventroposterolateral pallidotomy in the treatment of akinesia and rigidity is not a new discovery and agrees with recent investigations into the pathogenesis of Parkinson's disease, which highlight the role played by the unbridled activity of the subthalamic nucleus (STN) and the consequent overactivity of the globus pallidus internalis (GPi). Because high-frequency stimulation can reversibly incapacitate a nerve structure, we applied stimulation to the same target. Seven patients suffering from severe Parkinson's disease (Stages III–V on the Hoehn and Yahr scale) and, particularly, bradykinesia, rigidity, and levodopa-induced dyskinesias underwent unilateral electrode implantation in the posteroventral GPi. Follow-up evaluation using the regular Unified Parkinson's Disease Rating Scale has been conducted for 1 year in all seven patients, 2 years in five of them, and 3 years in one. In all cases high-frequency stimulation has alleviated akinesia and rigidity and has generally improved gait and speech disturbances. In some cases tremor was attenuated. In a similar manner, the authors observed a marked diminution in levodopa-induced dyskinesias. This could be an excellent primary therapy for younger patients exhibiting severe bradykinesia, rigidity, and levodopa-induced dyskinesias, which would allow therapists to keep ventroposterolateral pallidotomy in reserve as a second weapon.

Characteristics and somatotopic organization of kinesthetic cells in the globus pallidus of patients with Parkinson's disease

1996 ◽  
Vol 85 (6) ◽  
pp. 1005-1012 ◽  
Author(s):  
Jamal M. Taha ◽  
Jacques Favre ◽  
Thomas K. Baumann ◽  
Kim J. Burchiel
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Globus Pallidus ◽  
Passive Movement ◽  
Content Type ◽  
Somatotopic Organization ◽  
Different Characteristics ◽  
Distal Joint ◽  
Globus Pallidus Externus ◽  
Fine Print

✓ Information is limited on the characteristics and topographic localization of pallidal kinesthetic cells in patients with Parkinson's disease. The authors analyzed the data from 298 neurons recorded in 38 patients with Parkinson's disease who underwent pallidotomy via microrecording techniques. Sixty-five neurons (22%) responded to passive movement of contralateral limbs. Of 17 kinesthetic cells that were tested in six patients, seven (41%) responded to ipsilateral limb movement as well. Nineteen cells (6%) fired synchronously with tremor. More kinesthetic cells were activated (63%) than inhibited (28%) by movement of single (68%) rather than multiple (32%) joints, and proximal (75%) rather than distal (25%) joints. The lateral globus pallidus externus (GPe) and medial globus pallidus internus (GPi) pallidal segments contained similar proportions of kinesthetic cells, activated or inhibited cells, arm- or leg-activated cells, and cells responding to single or multiple joints. Significantly more kinesthetic cells that responded to distal joints were recorded in GPi compared to GPe segments (p = 0.01). Arm and leg cells had similar characteristics pertaining to activation versus inhibition and responses to single, multiple, proximal, or distal joint movements. Arm and leg cells were somatotopically organized in GPi. Arm cells were clustered at the rostral and caudal segments of GPi and leg cells were clustered centrally. In GPe, leg cells were clustered at the caudal border. No somatotopic organization was identified for activated or inhibited cells; cells that responded to single, multiple, proximal, or distal joints; tremor-synchronous cells; or cells responding to specific joints within somatotopic arm or leg cells. It is concluded that kinesthetic cells provide a roadmap that localizes limb cells during pallidotomy. More studies are needed to identify the clinical significance of the different characteristics of kinesthetic cells.

Gamma knife radiosurgery as a lesioning technique in movement disorder surgery

1998 ◽  
Vol 89 (2) ◽  
pp. 183-193 ◽  
Author(s):  
Ronald F. Young ◽  
Anne Shumway-Cook ◽  
Sandra S. Vermeulen ◽  
Peter Grimm ◽  
John Blasko ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Movement Disorder ◽  
Gamma Knife ◽  
Movement Disorders ◽  
Gamma Knife Radiosurgery ◽  
Safety And Efficacy ◽  
Content Type ◽  
Fine Print

Object. To increase knowledge of the safety and efficacy of the use of gamma knife radiosurgery in patients with movement disorders, the authors describe their own experience in this field and include blinded independent assessments of their results. Methods. Fifty-five patients underwent radiosurgical placement of lesions either in the thalamus (27 patients) or globus pallidus (28 patients) for treatment of movement disorders. Patients were evaluated pre- and postoperatively by a team of observers skilled in the assessment of gait and movement disorders who were blinded to the procedure performed. The observers were not associated with the surgical team and concomitantly and blindly also assessed a group of 11 control patients with Parkinson's disease who did not undergo any surgical procedures. All stereotactic lesions were made with the Leksell gamma unit using the 4-mm secondary collimator helmet and a single isocenter with maximum doses from 120 to 160 Gy. Clinical follow-up evaluation indicated that 88% of patients who underwent thalamotomy became tremor free or nearly tremor free. Statistically significant improvements in performance were noted in the independent assessments of Unified Parkinson's Disease Rating Scale (UPDRS) scores in the patients undergoing thalamotomy. Of patients undergoing pallidotomy who had exhibited levodopainduced dyskinesias, 85.7% had total or near-total relief of that symptom. Clinical assessment indicated improvements in bradykinesia and rigidity in 64.3% of patients who underwent pallidotomy. Independent blinded assessments did not reveal statistically significant improvements in Hoehn and Yahr scores or UPDRS scores. On the other hand, 64.7% of patients showed improvements in subscores of the UPDRS, including activities of daily living (58%), total contralateral score (58%), and contralateral motor scores (47%). Total ipsilateral score and ipsilateral motor scores were both improved in 59% of patients. One (1.8%) of 55 patients experienced a homonymous hemianopsia 9 months after pallidotomy due to an unexpectedly large lesion. No other complications of any kind were seen. Neuropsychological test scores that were obtained for the combined pallidotomy and thalamotomy treatment groups preoperatively and at 6 months postoperatively demonstrated an absence of cognitive morbidity. Follow-up neuroimaging confirmed correct lesion location in all patients, with a mean maximum deviation from the planned target of 1 mm in the vertical axis. Measurements of lesions at regular intervals on postoperative magnetic resonance images demonstrated considerable variability in lesion volumes. The safety and efficacy of functional lesions made with the gamma knife appear to be similar to those made with the assistance of electrophysiological guidance with open functional stereotactic procedures. Conclusions. Functional lesions may be made safely and accurately using gamma knife radiosurgical techniques. The efficacy is equivalent to that reported for open techniques that use radiofrequency lesioning methods with electrophysiological guidance. Complications are very infrequent with the radiosurgical method. The use of functional radiosurgical lesioning to treat movement disorders is particularly attractive in older patients and in those with major systemic diseases or coagulopathies; its use in the general movement disorder population seems reasonable as well.

Predictors of neuropsychological outcome in patients following microelectrode-guided pallidotomy for Parkinson's disease

2000 ◽  
Vol 93 (3) ◽  
pp. 410-420 ◽  
Author(s):  
Alois A. Obwegeser ◽  
Ryan J. Uitti ◽  
John A. Lucas ◽  
Robert J. Witte ◽  
Margaret F. Turk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuropsychological Performance ◽  
Neuropsychological Outcome ◽  
Semantic Fluency ◽  
Patient Age ◽  
Content Type ◽  
Patient Âgé ◽  
Neuropsychological Changes ◽  
Fine Print

Object. The authors studied neuropsychological performance following microelectrode-guided posteroventral pallidotomy in patients with Parkinson's disease (PD) and evaluated correlations with presurgical and surgical factors.Methods. Neuropsychological changes 3 months (43 patients) and 12 months (27 patients) after microelectrode-guided pallidotomy for PD are reported in a series of 44 consecutive patients with the disease, who improved neurologically, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) in both the “off” (p < 0.001) and best “on” (p < 0.001) states.Findings of the vocabulary subtest of the Wechsler Adult Intelligence Scale—Revised (p < 0.01), Letter Fluency (p < 0.001), Verbal Fluency for semantic categories (p < 0.001), and the Wisconsin Card Sorting Test (p < 0.01) showed a significant decline in neuropsychological performance in patients 3 months after undergoing left-sided pallidotomy. Impairment in the language domain (semantic fluency) persisted at the 12-month follow-up examination (p < 0.01). Visual memory improved after right-sided pallidotomies (p < 0.01 after 3 months), with a nonsignificant trend toward persistent improvement 1 year postsurgery (p < 0.02 after 12 months). Preoperative semantic fluency was influenced by patient age (p < 0.001) and by the width of the third ventricle (p < 0.05), as measured by magnetic resonance imaging.A regression model revealed that semantic fluency 3 months postoperatively was significantly affected by the baseline score (p < 0.001), side of surgery (p < 0.001), handedness (p < 0.01), and patient age (p < 0.05). However, postoperative lesion volume, lesion location, number of tracks, number of lesions, distance from anatomical landmarks, or UPDRS score did not significantly contribute to neuropsychological outcome.Conclusions. Neuropsychological changes in a cohort of patients with PD who underwent pallidotomy and experienced excellent clinical benefits and minimum postoperative complications, emphasize the importance of neuropsychological examinations and further investigation of predictive factors.

Brain targets in surgery for Parkinson's disease

1985 ◽  
Vol 62 (3) ◽  
pp. 349-351 ◽  
Author(s):  
Lauri V. Laitinen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
White Matter ◽  
Great Variability ◽  
Content Type ◽  
Fine Print

✓ Sixteen neurosurgeons were requested to define their preferred surgical target for treatment of parkinsonism. The scattergram thus obtained showed a great variability among surgeons. Although there was a concentration of targets in the ventrolateral (VL) nucleus of the thalamus, there was a separation by as much as 6 to 7 mm between targets. One surgeon placed the lesion in the subthalamic white matter below the VL nucleus, and two placed it outside the thalamus in the pallidothalamic pathways in Forel's field. It is assumed that successful surgery interrupts the pallidothalamocortical pathways that transmit tremor and rigidity impulses, regardless of which part of the pathways is severed.

Prefrontal dysfunction following unilateral posteroventral pallidotomy in Parkinson's disease

1999 ◽  
Vol 90 (6) ◽  
pp. 1005-1010 ◽  
Author(s):  
Tetsuo Yokoyama ◽  
Yoko Imamura ◽  
Kenji Sugiyama ◽  
Shigeru Nishizawa ◽  
Naoki Yokota ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Function ◽  
Digit Span ◽  
Preoperative Evaluation ◽  
Word Fluency ◽  
Yahr Stage ◽  
Content Type ◽  
Posteroventral Pallidotomy ◽  
Fine Print

Object. Pre- and postoperative cognitive function was evaluated in patients with Parkinson's disease (PD) who underwent unilateral posteroventral pallidotomy (PVP) to clarify the effects of this operation on cognitive function.Methods. Cognitive function was assessed before surgery and 1 month and 3 months afterward by using a battery of neuropsychological tests consisting of orientation, digit span (forward and backward), digit learning, 5-minute memory of five words, similarities, serial sevens, animal name listing, and the kana pick-out test, as well as the Japanese version of the Mini-Mental State. Preoperative evaluation revealed that patients experienced difficulties in performing the neuropsychological tasks of reasoning and abstraction, working memory of numerals, word fluency, and concept formation compared with 36 healthy volunteers (p < 0.05). A simple regression analysis showed strong relationships in a negative fashion between preoperative (r = 0.81, p = 0.002) and 1-month (r = 0.79, p = 0.0059) and 3-month (r = 0.85, p = 0.0016) postoperative gross-total scores and Hoehn and Yahr staging. Preoperative and postoperative scores at 1 month and 3 months were analyzed by analysis of variance, but only the Fisher's post hoc test revealed the source of difference. All tasks except orientation (p = 0.0292) were unchanged in the 10 patients who underwent surgery on the right side. The scores for this task at 1 month postsurgery were significantly lower (p = 0.0203) but improved to preoperative values by 3 months. In the 15 patients who underwent surgery on the left side significant differences among tasks were revealed for serial sevens (p = 0.0471) and animal naming (p = 0.0425). The scores for these tasks were significantly lower at 1 month postoperatively (p = 0.0431 for serial sevens and p = 0.0408 for animal naming), but improved by 3 months after the operation.Conclusions. The present data revealed that cognitive dysfunction in patients with PD relates to advancement of Hoehn and Yahr stage, but PVP is not associated with significant long-lasting cognitive deficits.

Preparation of adrenal medullary tissue for transplantation in Parkinson's disease: a new procedure

1989 ◽  
Vol 71 (3) ◽  
pp. 452-454 ◽  
Author(s):  
Juan J. López-Lozano ◽  
Begoña Brera ◽  
Javier Abascal ◽  
Gonzalo Bravo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adrenal Gland ◽  
Caudate Nucleus ◽  
Culture Medium ◽  
Content Type ◽  
Potential Value ◽  
Medullary Tissue ◽  
And Storage ◽  
Fine Print

✓ The authors describe a technique by which adrenal medullary tissue can be easily dissected from the adrenal cortex. The method involves perfusion with Locke's modified buffer, dissection of adrenal gland in buffer free of calcium or magnesium, and storage in a culture medium before implantation into the caudate nucleus of patients with Parkinson's disease. This method seems to increase the viability and purity of adrenal medullary tissue. The results obtained in 15 parkinsonian patients implanted with perfused adrenal medulla indicate the potential value of this technique.

Fatal cyst formation after fetal mesencephalic allograft transplant for Parkinson's disease

1998 ◽  
Vol 89 (4) ◽  
pp. 592-598 ◽  
Author(s):  
Adam N. Mamelak ◽  
Faye A. Eggerding ◽  
Daniel S. Oh ◽  
Erika Wilson ◽  
Richard L. Davis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Choroid Plexus ◽  
Cyst Formation ◽  
Mural Nodule ◽  
Content Type ◽  
Allograft Tissue ◽  
The Brain ◽  
Tissue Transplant ◽  
Fine Print

Object. In recent years, fetal mesencephalic tissue transplant for the treatment of Parkinson's disease (PD) has been demonstrated to hold promise, but potential complications related to growth of allograft tissue have not been well described. This report explores the development and possible causation of a fatal cyst arising from a fetal transplant in the brain. Methods. The authors report the case of a 52-year-old woman who underwent bilateral putamenal fetal mesencephalic allograft transplant for PD at another hospital. Twenty-three months later she presented to the authors' institution in a coma. Admission computerized tomography and magnetic resonance (MR) studies revealed a contrast-enhancing mural nodule and associated large cyst arising from the left putamen and causing brainstem compression. Despite surgical decompression of the cyst, the patient did not regain consciousness. Biopsy and autopsy specimens were obtained, along with an analysis of the cyst fluid. Genotyping of the nodule and the patient's peripheral lymphocytes by using polymerase chain reaction—based microsatellite analysis was also performed. Biopsy samples and autopsy histopathological studies showed inflammatory cells, hemosiderin-laden macrophages, and astrocytosis. Scattered neurons and multiple rests of choroid plexus were also noted. The cyst had a thin wall and contained liquid that was identical in composition to cerebrospinal fluid (CSF). Genotyping demonstrated the presence of alleles in the nodule DNA that were not present in lymphocytic DNA, indicating that the nodule contained allograft tissue. Conclusions. The authors hypothesize that the choroid plexus tissue contained in the allograft resulted in CSF production and cyst formation at the transplant site, ultimately leading to the patient's herniation syndrome. The clinical history and large size of the mural nodule indicate slow growth of this allograft site and cyst over time. This case demonstrates that unusual patterns of tissue growth can occur in the brain after fetal tissue transplant and emphasizes the need for long-term monitoring of posttransplant patients by means of MR imaging. Cell sorting should be considered to ensure transplant of pure neuronal and astroglial populations.

Long-term improvement in patients with severe Parkinson's disease after implantation of fetal ventral mesencephalic tissue in a cavity of the caudate nucleus: 5-year follow up in 10 patients

1997 ◽  
Vol 86 (6) ◽  
pp. 931-942 ◽  
Author(s):  
Juan J. López-Lozano ◽  
Gonzalo Bravo ◽  
Begoña Brera ◽  
Isabel Millán ◽  
Jose Dargallo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caudate Nucleus ◽  
Adrenal Medulla ◽  
Open Surgery ◽  
Clinical Symptoms ◽  
Content Type ◽  
Ventral Mesencephalic ◽  
Fine Print

✓ Different groups worldwide have observed in recent years that stereotactic implantation of fetal tissue can ameliorate the clinical symptoms of Parkinson's disease. The authors therefore investigated whether implantation of fetal ventral mesencephalic (FVM) tissue via open surgery is also capable of producing an improvement and whether this improvement is transient or long lasting. The authors report their findings in a 5-year follow-up study in 10 patients with Hoehn and Yahr Grade IV or V Parkinson's disease in whom a single FVM graft was implanted in a cavity created in the right caudate nucleus. The results indicate that the implants improved motor function and that clinical recovery persisted in seven of the 10 patients 5 years after implantation. Amelioration was observed in both the on and off phases and was accompanied by a 64% reduction in the levodopa dose and withdrawal of the dopamine agonist. The on phase was prolonged from 39% of the waking day to 72%, with reduced intensity and duration of dyskinesias. All symptoms that were analyzed showed improvement, although they differed in intensity and time of onset. The course of improvement seemed to be stepwise, with significant improvement between 5 and 7 months postimplantation followed by two waves of progress peaking in Months 15 and 36. Withdrawal of cyclosporine in three patients after more than 2 years of administration produced a decline in the patients' clinical conditions. In conclusion, the results indicate that open surgery implantation of FVM tissue in the caudate nucleus improves the clinical condition of parkinsonian patients and that this improvement can persist for at least 5 years. In comparison with two earlier series reported by the authors, which involved implants of perfused adrenal medulla and coimplantation of adrenal medulla and peripheral nerve, the course and pattern of improvement in these implant recipients suggests that their recovery can be attributed to more than one factor.

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