stereotactic transplantation foetalventral mesencephalic cells:...

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Stereotactic Transplantation of Foetal Ventral MesencephalicCells: Cuban Experience from Five Patients with Idiopathic

Parkinson’s DiseaseH. Molina, R. Quifiones, L. Alvarez, I. Ortega, J.L. Mufioz, C. Gonzlez, K. de la Cu6tera,O. Torres, C. Surez, M. Le6n, M.J. Rojas, M. Rachid, R. Maeas, J.C. Garea, N. Pav6n,

L. Lorigados, O. Castellanos and O. Hernndez

Centro Iberolatinoamecano de Transplante y Regeneracin del Sistema Nervioso,Avenida 25 # 15805, entre 158y 160, Playa, Ciudad de La Habana, Cuba

From April to December 1987, after havingcarried out rodent neurografting studies, weperformed adrenal medulla autotransplantationon three patients with severe Parkinson’s dis-ease. From January 1988 to April 1990, thirtyparkinsonian patients underwent foetal ventralmesencephalic tissue transplantation in thecaudate nucleus, using an open microsurgicalprocedure.

The stereotactic neurotransplantation tech-nique was first applied in Cuba in March 1992.Five patients with idiopathic Parkinson’s disease(Hoehn & Yahr Stage 4) were selected accord-ing to CAPIT criteria. Their mean age at time ofsurgery was 51 years, the evolution time of thedisease ranged from 7 to 13 years; and they hadbeen receiving L-Dopa for a mean period of 9years. All of them had motor complicationsassociated with chronic L-Dopa therapy, such asdyskinesias, freezing, and complex fluctuationsin motor condition. The presurgical mean "off’time was 57.6% of the waking day, but in "on"conditions the patients spent 11.2% of the daywith disabling dyskinesias.

Using the Leksell Stereotactic System, weperformed computer-assisted CT-guided stereo-tactic transplantation of foetal ventral mesen-cephalic cell suspensions, into the right caudateand putamen. The post-conception ages offoetuses were 8-13 weeks; the mean time be-tween abortion and implantation was 2 hours 42minutes; and the graft cell viability ranged from52 to 80%.

The clinical assessment of the patients carriedout during twelve months before surgery andthree months after transplantation revealed a

progressive reduction in both the daily timespent in "off’ conditions from 57.6% beforesurgery to 12.5% three months after transplanta-tion, and the number of daily "off’ periods perday from 4.4 to 1.5.

In the 3rd post-operative month, the patientsshowed, as a general pattern, a significantimprovement in their neurological performance(from 108.8 to 59.5 in I[DRS), a less severe dis-ability during "off’ periods (Fig. 1), and increaseof "on" time predominantly without dyskinesias(from 31 to 89%), according to internationalrating scales for Parkinson’s disease.

Timed neurological tests were performed inthe post-surgical periods before and after thefirst daily L-Dopa dose. Beginning in the 7thweek after grafting there was a significant bi-lateral improvement of movement speed in both"off’ and "on" periods, mainly contralateral tothe transplantation site, and a progressivereduction of the pre-surgical differencesbetween "off’ and "on" performance time.

In the post-operative stage, we adopted thepharmacotherapeutic strategy of administeringL-Dopa in slowly increasing doses, to obtain thebest neurological conditions. The patients’sensitivity to L-Dopa increased after transplan-tation, allowing us a wider time interval betweendoses, and a gradual reduction of the mean dosefrom 1000 mg per day before surgery to 409.5mg daily, three months after implantation.

Dopaminergic drug responses were assessedbefore and after surgery. The results of thepharmacological tests proved post-operativechanges in the pattern of the single dose L-Doparesponse: the motor performance improved sig-

(C) FREUND PUBLISHING HOUSE LTD., LONDON. JOURNAL OF NEURAL TRANSPLANTATION & PLASTICITY, Vol. 3, No. 4, 1992

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Clinic volutionPDRS) , p<O.05 Wilcoxon Matched Pairs Test

Pre. 30 60 90

MEAN,St. Err.

T St. Dev.

Assessment times (days)

Clinical evolution from 12 months before to 3 months after transplantation.Progressive clinical improvement statistically significant from to 3 months after grafting (P_<O.05)(Wilcoxon matched pairs test).

nificantly, the "on" latency shortened from 76minutes pre-surgery to 25 minutes three monthsafter grafting, and the beneficial time-effect ofL-Dopa increased from 84 minutes before to 265minutes in the 3rd post-operative month.

The post-surgical improvement in ourpatients can be summarized as follows-

Motor complications associated with L-Dopatherapy: redneed.Response to L-Dopa treatment: improved.Daily requirements of L-Dopa: redneed.Parkinsonian symptoms: redneed.Neurological performance: improved.Quality of life: improved.

Finally, based on the research conducted overmore than four years in the field of neuraltransplantation and as a result of our mostrecent experiences, we conclude that transplan-tation of dopaminergic cells may improve theneurological condition of parkinsonian patientssuffering from motor complications associatedwith L-Dopa therapy.

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