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.

Clinical outcome of cotransplantation of peripheral nerve and adrenal medulla in patients with Parkinson's disease

1999 ◽  
Vol 90 (5) ◽  
pp. 875-882 ◽  
Author(s):  
Juan J. López-Lozano ◽  
Gonzalo Bravo ◽  
Javier Abascal ◽  
Begoña Brera ◽  
Isabel Millan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Peripheral Nerve ◽  
Caudate Nucleus ◽  
Adrenal Medulla ◽  
Intercostal Nerve ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Content Type ◽  
Fine Print

Object. Transplants of adrenal medulla (AM) and fetal ventral mesencephalon (FVM) are currently being tested as therapeutic alternatives in patients with Parkinson's disease (PD). At the Clínica Puerta de Hierro in Madrid, a controlled clinical trial is underway to establish which donor tissue, if any, is the best for open surgical implantation in patients with PD.Methods. Since 1987, varying degrees of clinical improvement have been achieved in Grade IV and V parkinsonian patients by implanting perfused AM and FVM into the right caudate nucleus. To investigate further whether implantation of different types of donor tissues results in qualitatively and quantitatively different degrees of recovery, four patients with Grade IV or V PD received implants of pre-coincubated autologous AM and intercostal nerve in the caudate nucleus. Four nonsurgically treated patients served as a control group. Three years posttransplantation, longer on phases (46.2% ± 10.4% of the day presurgery to 87.5% ± 10.4% of the day 36 months postsurgery) and improved symptoms in on and off phases persist in all four cases, with reduced dyskinesias (67.1% ± 9.2% of the day in on phases presurgery to 17% ± 13.8% of the day in on phases 36 months postsurgery). Progress appears to be stepwise, starting within weeks of tranplantation and becoming clinically significant in the 2nd and 3rd months (similar to our AM- and sooner than in our FVM-implanted patients), followed by a period of stability and, after a second wave of improvement 12 to 18 months posttransplantation (similar to FVM implants), has continued (87.5 ± 7 points presurgery to 46 ± 5.6 points 36 months postsurgery). In the experimental group, doses of levodopa have been reduced by more than 60% and dopamine agonist use has not resumed. In contrast, there have been no significant clinical changes in the control group.Conclusions. Implantation of tissue other than fetal tissue can promote a long-term improvement in the clinical symptomatology of seriously disabled parkinsonian patients. This finding is supported by the autopsy report of a patient with PD who had undergone grafting of AM plus peripheral nerve in which it was demonstrated that a large number of tyrosine hydroxylase—positive cells survive 1 year after implantation. In addition, there was a dense network of host dopaminergic fibers around the graft.

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.

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.

Gamma knife thalamotomy for treatment of tremor: long-term results

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 128-135 ◽  
Author(s):  
Ronald F. Young ◽  
Skip Jacques ◽  
Rufus Mark ◽  
Oleg Kopyov ◽  
Brian Copcutt ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Essential Tremor ◽  
Gamma Knife ◽  
Rating Scale ◽  
Long Term Results ◽  
Content Type ◽  
Fine Print

Object. The purpose of this study was to investigate the long-term effects of gamma knife thalamotomy for treatment of disabling tremor. Methods. One hundred fifty-eight patients underwent magnetic resonance imaging—guided radiosurgical nucleus ventralis intermedius (VIM) thalamotomy for the treatment of parkinsonian tremor (102 patients), essential tremor (52 patients), or tremor due to stroke, encephalitis, or cerebral trauma (four patients). Preoperative and postoperative blinded assessments were performed by a team of independent examiners skilled in the evolution of movement disorders. A single isocenter exposure with the 4-mm collimator helmet of the Leksell gamma knife unit was used to make the lesions. In patients with Parkinson's disease 88.3% became fully or nearly tremor free, with a mean follow up of 52.5 months. Statistically significant improvements were seen in Unified Parkinson's Disease Rating Scale tremor scores and rigidity scores, and these improvements were maintained in 74 patients followed 4 years or longer. In patients with essential tremor, 92.1% were fully or nearly tremor free postoperatively, but only 88.2% remained tremor free by 4 years or more post-GKS. Statistically significant improvements were seen in the Clinical Rating Scale for tremor in essential tremor patients and these improvements were well maintained in the 17 patients, followed 4 years or longer. Only 50% of patients with tremor of other origins improved significantly. One patient sustained a transient complication and two patients sustained mild permanent side effects from the treatments. Conclusions. Gamma knife VIM thalamotomy provides relief from tremor equivalent to that provided by radiofrequency thalamotomy or deep brain stimulation, but it is safer than either of these alternatives. Long-term follow up indicates that relief of tremor is well maintained. No long-term radiation-induced complications have been observed.

Stereotactic ventrolateralis thalamotomy for medically refractory tremor in post-levodopa era Parkinson's disease patients

1991 ◽  
Vol 75 (5) ◽  
pp. 723-730 ◽  
Author(s):  
Mark W. Fox ◽  
J. Eric Ahlskog ◽  
Patrick J. Kelly
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mayo Clinic ◽  
Microelectrode Recording ◽  
Stereotactic Techniques ◽  
Content Type ◽  
Resting Tremor ◽  
Fine Print

✓ Thirty-six patients with Parkinson's disease and medically refractory tremor underwent stereotactic ventrolateralis thalamotomy at the Mayo Clinic between 1984 and 1989. All patients had been or were being treated with carbidopa/levodopa but with unsatisfactory tremor control. Modern stereotactic techniques, including microelectrode recording, were used to treat 36 patients, of whom 31 (86%) had complete abolition of tremor and three patients (5%) had significant improvement. Tremor recurred in two patients within 3 months of surgery; however, the remaining patients suffered no recurrence of tremor during follow-up periods ranging from 14 to 68 months (mean 33 months). Persistent complications (arm dyspraxia, dysarthria, dysphasia, or abulia) were noted in five patients but were a source of disability in only two. It is concluded that thalamotomy in carefully selected patients is a beneficial operation for the control of medically refractory parkinsonian resting tremor.

Autotransplantation of the superior cervical ganglion into the brain

1988 ◽  
Vol 68 (6) ◽  
pp. 955-959 ◽  
Author(s):  
Toru Itakura ◽  
Ichiro Kamei ◽  
Kunio Nakai ◽  
Yutaka Naka ◽  
Kazuo Nakakita ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebral Cortex ◽  
Caudate Nucleus ◽  
Superior Cervical Ganglion ◽  
Content Type ◽  
Cervical Ganglion ◽  
6 Hydroxydopamine ◽  
The Brain ◽  
Fine Print

✓ The superior cervical ganglion (SCG) of rats was transplanted into their own parietal cortex. Four weeks after implantation, catecholamine histofluorescence revealed many transplanted catecholamine cells in the cortex. However, no fibers extended from the transplanted tissue to the cerebral cortex. In a second group of rats which had been pretreated with 6-hydroxydopamine (a specific neurotoxin to the catecholamine neuron), some showed extension of catecholamine fibers to the cerebral cortex. To simulate an animal model of Parkinson's disease, MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) was administered to five monkeys. Two weeks after MPTP administration, dopamine terminals in the caudate nucleus disappeared. After autotransplantation of the SCG into the caudate nucleus of these monkeys, many of the transplanted SCG cells extended axons beyond the graft into the caudate nucleus. These results show that transplanted SCG cells survived well in the brain. Under special circumstances, such as a shortage of catecholamine in the brain, implanted SCG cells extended their axons into the brain. It is suggested that autotransplantation of SCG grafts may be a new therapy for Parkinson's disease.

scholarly journals Autologous Transplantation of Adrenal Medulla Into the Caudate Nucleus: A Four Year Follow Up Study

1992 ◽  
Vol 3 (4) ◽  
pp. 290-291
Author(s):  
E. Garcia-Flores ◽  
A. Martinez-Campos ◽  
R. Farias
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caudate Nucleus ◽  
Effective Treatment ◽  
Adrenal Medulla ◽  
Autologous Transplantation ◽  
Morbidity And Mortality ◽  
Follow Up Study

The objective of this study was to determine whether the associated morbidity and mortality of adrenal medulla autologous transplantation into the striatum (open transcortical procedure) justifies this as a safe and effective treatment for Parkinson's Disease (PD).

Pallidal stimulation for generalized dystonia

2000 ◽  
Vol 92 (3) ◽  
pp. 453-456 ◽  
Author(s):  
Volker M. Tronnier ◽  
Wolfgang Fogel
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stereotactic Surgery ◽  
Treatment Alternative ◽  
Content Type ◽  
Pallidal Stimulation ◽  
Generalized Dystonia ◽  
Fine Print

✓ Pallidal stereotactic surgery is a well-accepted treatment alternative for Parkinson's disease. Another indication for this procedure is medically refractory dystonia, especially generalized dystonia with abnormal axial and extremity movements and postures. Improvement of dystonia after pallidotomy has been reported in several recent papers. In this report the authors describe three patients with generalized dystonia (two primary, one secondary) and their improvement after bilateral pallidal stimulation at follow-up times of between 6 and 18 months.

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.

Long-term follow-up results of selective VIM-thalamotomy

1986 ◽  
Vol 65 (3) ◽  
pp. 296-302 ◽  
Author(s):  
Yoshishige Nagaseki ◽  
Tohru Shibazaki ◽  
Tatsuo Hirai ◽  
Yasuhiro Kawashima ◽  
Masafumi Hirato ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Essential Tremor ◽  
The Other ◽  
Content Type ◽  
Early Results ◽  
Initial Surgery ◽  
Long Term Follow Up

✓ The authors report the results of a long-term follow-up study of the effects of the physiologically defined selective VIM (nucleus ventralis intermedius)-thalamotomy on tremor of Parkinson's disease in 27 patients and essential tremor in 16 patients. The follow-up period ranged from 3.25 to 10 years (mean 6.58 years). In 43 patients a total of 50 operations (including four bilateral operations and three reoperations) were carried out. The early (2 to 4 weeks after surgery) and late effects on the tremors were determined clinically and electromyographically. Fourteen parkinsonian cases were treated with minimal lesions (about 40 cu mm). Their late results were very similar to the early results: in 10, the tremors were completely abolished, three had a slight residual tremor, and one underwent reoperation 3 months after the first surgery. Eleven essential tremor cases were treated with minimal lesions. Six of these tremors were completely abolished, four patients had slight residual tremors, and one patient with a recurrence underwent reoperation 2 years after the initial surgery. In these 23 successful operations with minimal lesions (excluding two cases with reoperation), the tremor was abolished without discernible long-lasting side effects. The other 23 operations on 16 patients with Parkinson's disease (including one reoperation) and on seven with essential tremor (one of whom also had a minimal lesion on the other side) involved relatively large lesions. In this group, the surgery was successful in almost every case. It was concluded that radiographically and physiologically monitored selective VIM-thalamotomy for parkinsonian and essential tremor is effective even when lesioning is minimal. Moreover, the beneficial effect is maintained over a long period of time.

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