Chromaffin cell survival and host dopaminergic fiber recovery in a patient with Parkinson's disease treated by cografts of adrenal medulla and pretransected peripheral nerve

✓ A 55-year-old woman with severe Parkinson's disease was treated by cografting adrenal medulla with pretransected peripheral nerve into the bilateral caudate nuclei. The patient showed modest improvement of her akinesia; this effect persisted for 1 year after transplantation, when she suddenly died from upper gastrointestinal bleeding unrelated to the grafting procedure. At autopsy, a large number of tyrosine hydroxylase—immunoreactive chromaffin cells were observed within the caudate graft sites and a dense network of host dopaminergic fibers was visualized. This autopsy finding is very important for the field of experimental and clinical chromaffin cell grafting because it is the first evidence that cografts using pretransected peripheral nerve might enhance the survival of chromaffin cells and the recovery of host dopaminergic fibers in humans suffering from Parkinson's disease.

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Two-year Follow-up Study of a Patient with Parkinson's Disease and Severe Motor Fluctuations Treated by Co-grafts of Adrenal Medulla and Peripheral Nerve into Bilateral Caudate Nuclei

Neurosurgery ◽

10.1227/00006123-199509000-00022 ◽

1995 ◽

Vol 37 (3) ◽

pp. 515-519 ◽

Cited By ~ 22

Author(s):

Isao Date ◽

Shoji Asari ◽

Takashi Ohmoto

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Peripheral Nerve ◽

Adrenal Medulla ◽

Motor Fluctuations ◽

Caudate Nuclei ◽

Follow Up Study ◽

Severe Motor

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

Journal of Neurosurgery ◽

10.3171/jns.1999.90.5.0875 ◽

1999 ◽

Vol 90 (5) ◽

pp. 875-882 ◽

Cited By ~ 11

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.

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Co-transplantation of peripheral nerve and adrenal medulla in Parkinson's disease

The Lancet ◽

10.1016/0140-6736(92)90115-j ◽

1992 ◽

Vol 339 (8790) ◽

pp. 430 ◽

Cited By ~ 13

Author(s):

JuanJ. López Lozano ◽

Gonzalo Bravo ◽

Javier Abascal ◽

B. Brera ◽

H. Santos ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Peripheral Nerve ◽

Adrenal Medulla

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NGF-like trophic support from peripheral nerve for grafted rhesus adrenal chromaffin cells

Journal of Neurosurgery ◽

10.3171/jns.1990.73.3.0418 ◽

1990 ◽

Vol 73 (3) ◽

pp. 418-428 ◽

Cited By ~ 126

Author(s):

Jeffrey H. Kordower ◽

Massimo S. Fiandaca ◽

Mary F. D. Notter ◽

John T. Hansen ◽

Don M. Gash

Keyword(s):

Tyrosine Hydroxylase ◽

Adrenal Medulla ◽

Sural Nerve ◽

Chromogranin A ◽

Chromaffin Cells ◽

Chromaffin Cell ◽

Adrenal Chromaffin Cells ◽

Content Type ◽

Adrenal Chromaffin ◽

Fine Print

✓ Autopsy results on patients and corresponding studies in nonhuman primates have revealed that autografts of adrenal medulla into the striatum, used as a treatment for Parkinson's disease, do not survive well. Because adrenal chromaffin cell viability may be limited by the low levels of available nerve growth factor (NGF) in the striatum, the present study was conducted to determine if transected peripheral nerve segments could provide sufficient levels of NGF to enhance chromaffin cell survival in vitro and in vivo. Aged female rhesus monkeys, rendered hemiparkinsonian by the drug MPTP (n-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), received autografts into the striatum using a stereotactic approach, of either sural nerve or adrenal medulla, or cografts of adrenal medulla and sural nerve (three animals in each group). Cell cultures were established from tissue not used in the grafts. Adrenal chromaffin cells either cocultured with sural nerve segments or exposed to exogenous NGF differentiated into a neuronal phenotype. Chromaffin cell survival, when cografted with sural nerve into the striatum, was enhanced four- to eightfold from between 8000 and 18,000 surviving cells in grafts of adrenal tissue only up to 67,000 surviving chromaffin cells in cografts. In grafts of adrenal tissue only, the implant site consisted of an inflammatory focus. Surviving chromaffin cells, which could be identified by both chromogranin A and tyrosine hydroxylase staining, retained their endocrine phenotype. Cografted chromaffin cells exhibited multipolar neuritic processes and numerous chromaffin granules, and were also immunoreactive for tyrosine hydroxylase and chromogranin A. Blood vessels within the graft were fenestrated, indicating that the blood-brain barrier was not intact. Additionally, cografted chromaffin cells were observed in a postsynaptic relationship with axon terminals from an undetermined but presumably a host origin.

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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

Journal of Neurosurgery ◽

10.3171/jns.1997.86.6.0931 ◽

1997 ◽

Vol 86 (6) ◽

pp. 931-942 ◽

Cited By ~ 44

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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