Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: a long-term follow-up study.
BACKGROUND
Although we have shown in three out of five patients with Huntington's disease that motor and cognitive improvements 2 years after intracerebral fetal neural grafts are correlated with recovery of brain metabolic activity in grafted striatal areas and connected regions of the cerebral cortex, neural grafts are not known to have protective effects on the host brain per se. We undertook long-term follow-up of previously reported patients with the disease to ascertain the nature and extent of any secondary decline after grafting.


METHODS
Five patients with Huntington's disease from our pilot study were assessed annually with the unified Huntington's disease rating scale, neuropsychological tests, and MRI, for up to 6 years after neural grafting. Resting cerebral activity was recorded at 2 and 6 years.


RESULTS
Clinical improvement plateaued after 2 years and then faded off variably 4-6 years after surgery. Dystonia deteriorated consistently, whereas chorea did not. Cognitive performance remained stable on non-timed tests, whereas progression of motor disability was shown by deterioration on timed tests. Hypometabolism also affected the brain heterogeneously, sparing the benefits in the frontal cortex and at the precise location of the grafts, but showing a progressive deterioration in other areas. Two patients who had no benefit from grafting at 2 years continued to decline in the same way as non-grafted patients.


CONCLUSIONS
Neuronal transplantation in Huntington's disease provides a period of several years of improvement and stability, but not a permanent cure for the disease. Improvement of the surgical procedure and in patient selection could improve the therapeutic value, but neuroprotective treatment seems to be unavoidable in the disease.
Bachoud-Lévi
Anne-Catherine
AC
INSERM U 421, Faculté de Médecine, Créteil, France. bachoud@lscp.ehess.fr
Gaura
Véronique
V
Brugières
Pierre
P
Lefaucheur
Jean-Pascal
JP
Boissé
Marie-Françoise
MF
Maison
Patrick
P
Baudic
Sophie
S
Ribeiro
Maria-Joao
MJ
Bourdet
Catherine
C
Remy
Philippe
P
Cesaro
Pierre
P
Hantraye
Philippe
P
Peschanski
Marc
M
D000328:Adult; D016380:Brain Tissue Transplantation / Q000379:methods*; D003071:Cognition / Q000502:physiology; D004185:Disability Evaluation; D004622:Embryo, Mammalian; D016332:Fetal Tissue Transplantation / Q000379:methods*; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology / Q000601:surgery*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010865:Pilot Projects; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome