RSS-Feed abonnieren
Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.
https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000071.xml
PDF herunterladen
Semin Neurol 2001; 21(1): 091-102
DOI: 10.1055/s-2001-13124
DOI: 10.1055/s-2001-13124
Neurosurgery for Parkinson's Disease
Weitere Informationen
Publikationsverlauf
Publikationsdatum:
31. Dezember 2001 (online)
ABSTRACT
Medical therapy for Parkinson's disease (PD) often becomes inadequate over several years. Disability increases despite maximal medical management and many patients develop motor fluctuations and dyskinesia. In addition, medications provide good control of tremor in only 50% of cases. In appropriately selected cases, surgical therapies for PD provide benefit for medically refractory symptoms. Recent advances have provided a greater array of surgical options. Unilateral thalamotomy and thalamic stimulation are considered safe and effective procedures to treat contralateral tremor. Pallidotomy and pallidal stimulation primarily reduce contralateral dyskinesia, with lesser effects on bradykinesia and rigidity. Studies indicate that subthalamic nucleus (STN) stimulation improves ``off'' period function, decreases ``off'' time, and lessens dyskinesia. Fetal cell transplantation remains experimental, and studies are underway to evaluate the safety and efficacy of porcine fetal cell and human retinal pigment epithelial cell transplantation. This chapter reviews the history of surgical procedures for PD, describes current procedures, and offers a look into the future of neurosurgical options for PD.
KEYWORD
Parkinson's disease - surgery - thalamotomy - thalamic stimulation - pallidotomy - pallidal stimulation - subthalamic nucleus stimulation - fetal cell transplantation - porcine cell transplantation - human retinal pigment epithelial cell transplantation
REFERENCES
- 1 Koller W C, Busenbark K, Minor K, and the ET Study Group. Relationship of essential tremor to other movement disorders: report on 678 patients. Ann Neurol . 1994; 35 717-723
- 2 Lang A E, Lozano A M. Parkinson's disease. N Engl J Med . 1998; 339 1130-1143
- 3 Das K, Benzil D L, Rovit R. Irving S. Cooper (1922-1985): a pioneer in functional neurosurgery. J Neurosurg . 1988; 89 865-873
- 4 Meyers H R. The modification of alternating tremors, rigidity, and festination by surgery of the basal ganglia. Nerv Ment Dis . 1942; 21 602-665
- 5 Meyers H R. Surgical procedure for postencephalitic tremor, with notes on the physiology of the premotor fibers. Arch Neurol Psychiatry . 1940; 44 455-457
- 6 Bucy P C. Cortical extirpation in the treatment of involuntary movements. Res Nerv Ment Dis Proc . 1942; 21 551-595
- 7 Cooper I S, Bravo G J. Implications of a five-year study of 700 basal ganglia operations. Neurology . 1958; 8 344-346
- 8 Cooper I S, Bravo G J, Riklan M. Chemopallidectomy and chemothalamectomy for parkinsonism. Geriatrics . 1958; 13 127-144
- 9 Svennilson E, Torvik A, Lowe R, Leksell L. Treatment of parkinsonism by stereotactic thermolesions in the pallidal region. Acta Psychiatr Scand . 1960; 35 358-377
- 10 Mundinger F, Riechert T. Esgelnisse der sterotaktischen Hirnoperationen bei extrapyramidalen Bewegungsstrorungen auf Grund postoperativer und Langzeituntersuchungen. Dtsch Z Nervenheilkd . 1961; 182 5442-5576
- 11 Cooper I S. Parkinsonism: Its Medical and Surgical Therapy.
Springfield, IL: Charles C Thomas; 1961
MissingFormLabel
- 12 Spiegel E A, Wycis H T. Stereoencephalotomy: Part 2. Clinical and Physiological Applications
New York: Grune & Stratton; 1962
MissingFormLabel
- 13 Cooper I S. Surgical treatment of parkinsonism. Annu Rev Med . 1965; 16 309-330
- 14 Spiegel E A, Wycis H T, Marks M. Stereotactic apparatus for operation on the human brain. Science . 1947; 106 349-350
- 15 Spiegel E A, Wycis H T. Ansotomy in paralysis agitans. Arch Neurol Psychiatry . 1954; 71 598-614
- 16 Laitenen L V, Bergenheim A T, Hariz M I. Leskell's posteroventral pallidotomy in the treatment of Parkinson's disease. J Neurosurg . 1992; 76 53-61
- 17 Laitenen L V, Bergenheim A T, Hariz M I. Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms. Stereotact Funct Neurosurg . 1992; 58 14-21
- 18 Selby G. Stereotactic surgery for the relief of Parkinson's disease: Part I. A critical review. J Neurol Sci . 1967; 5 315-342
- 19 Tasker R R. Surgical aspects: symposium on extrapyramidal disease. Appl Ther . 1967; 9 454-462
- 20 Tasker R R, Siqueira J, Hawrylyshyn P. What happened to VIM thalamotomy for Parkinson's disease?. Appl Neurophysiol . 1983; 46 68-83
- 21 Kelly P J, Ahlskog J E, Goerss S J. Computer-assisted stereotactic ventralis lateralis thalamotomy with microelectrode recording in patients with Parkinson's disease. Mayo Clin Proc . 1987; 62 655-664
- 22 Matsumoto K, Schichijo F, Fukami T. Long-term follow-up review cases of Parkinson's disease after unilateral or bilateral thalamotomy. J Neurosurg . 1984; 60 1033-1044
- 23 Miyamoto T, Bekku H, Moriyama E. Present role of stereotactic thalamotomy for parkinsonism: retrospective analysis of operative results and thalamic lesions in computed tomograms. Appl Neurophysiol . 1985; 48 294-304
- 24 Mundinger F. Postoperative and long-term results of 1,561 stereotactic operations in parkinsonism. Appl Neurophysiol . 1985; 48 293
- 25 Narabayashi H, Maeda T, Yokochi F. Long-term follow-up results of selective VIM-thalamotomy. J Neurosurg . 1986; 65 296-302
- 26 Scott R M, Brody J A, Cooper I S. The effect of thalamotomy on the progress of unilateral Parkinson's disease. J Neurosurg . 1970; 32 286-288
- 27 Tasker R R. Thalamotomy. Neurol Clin . 1990; 1 841-864
- 28 Riechert T. Stereotactic Brain Operations: Methods, Clinical Aspects, Indications.
Bern: Hans Huber 1980: 213-304
MissingFormLabel
- 29 Linhares M N, Tasker R R. Microelectrode-guided thalamotomy for Parkinson's disease. Neurosurgery . 2000; 46 390-398
- 30 Fox M W, Ahlskog J E, Kelly P J. Stereotactic ventrolateralis thalamotomy for medically refractory tremor in post-levodopa era Parkinson's disease patients. J Neurosurg . 1991; 75 723-730
- 31 Osenbach R K, Burchiel K J. Thalamotomy: indications, techniques and results. In: Lozano AM, ed. Neurosurgical Treatment of Movement Disorders
Park Ridge: AANS 1998: 107-129
MissingFormLabel
- 32 Diederich N, Goetz C G, Stebbins G T. Blinded evaluation confirms long-term asymmetric effect of unilateral thalamotomy or subthalamotomy on tremor in Parkinson's disease. Neurology . 1992; 42 1311-1314
- 33 Moriyama E, Beck H, Miyamoto T. Long-term results of ventrolateral thalamotomy for patients with Parkinson's disease. Neurol Med Chir (Tokyo) . 1999; 39 350-356
- 34 Laitenen L V. Thalamic targets in stereotactic treatment of Parkinson's disease. J Neurosurg . 1966; 24 82-85
- 35 Lozano A, Hutchison W, Kiss Z, Tasker R, Davis K, Dostrovsky J. Methods for microelectrode-guided posteroventral pallidotomy. J Neurosurg . 1996; 84 194-202
- 36 Lang A E, Duff J, Saint-Cyr J A. Posteroventral medial pallidotomy in Parkinson's disease. J Neurol . 1999; 28-48 (28-48)
- 37 Laitenen L V, Bergenheim T, Hariz A L. Leksell's posteroventral pallidotomy in the treatment of Parkinson's disease. J Neurosurg . 1992; 76 53-61
- 38 Dogali M, Fazzini E, Kolodny E. Stereotactic ventral pallidotomy for Parkinson's disease. Neurology . 1995; 45 753-761
- 39 Lozano A M, Lang A E, Galvez-Jimenez N. Effect of Gpi pallidotomy on motor function in Parkinson's disease. Lancet . 1995; 346 1383-1387
- 40 Baron M S, Vitek J L, Bakay R AE. Treatment of advanced Parkinson's disease by posterior Gpi pallidotomy: 1-year results of a pilot study. Ann Neurol . 1996; 40 355-366
- 41 Uitti R J, Wharen R E, Turk M F. Unilateral pallidotomy for Parkinson's disease: comparison of outcome in younger versus elderly patients. Neurology . 1997; 49 1072-1077
- 42 Fazzini E, Dogali M, Sterio D. Stereotactic pallidotomy for Parkinson's disease: a long-term follow-up of unilateral pallidotomy. Neurology . 1997; 48 1273-1277
- 43 Merello M, Nouzeilles M I, Cammarotta A. Changes in the motor response to acute L-dopa challenge after unilateral microelectrode-guided posteroventral pallidotomy. Clin Neuropharmacol . 1998; 21 135-138
- 44 Jankovic J, Ben-Arie L, Schwartz K. Movement and reaction times and fine coordination tasks following pallidotomy. Mov Disord . 1999; 14 57-62
- 45 Iacono R P, Shima F, Lonser R R. The results, indications and physiology of posteroventral pallidotomy for patients with Parkinson's disease. Neurosurgery . 1995; 36 1118-1127
- 46 Lang A E, Lozano A M, Montgomery E. Posteroventral medial pallidotomy in advanced Parkinson's disease. N Engl J Med . 1997; 337 1036-1042
- 47 Sutton J P, Couldwell W, Lew M F. Ventroposterior medial pallidotomy on motor function in Parkinson's disease. Neurosurgery . 1995; 36 1112-1117
- 48 Ondo W G, Jankovic J, Lai E C. Assessment of motor function after stereotactic pallidotomy. Neurology . 1998; 50 266-270
- 49 Melnick M E, Dowling G A, Aminoff M J. Effect of pallidotomy on postural control and motor function in Parkinson's disease. Arch Neurol . 1999; 56 1361-1365
- 50 Martinez-Martin P, Valldeoriola F, Molinuevo J L. Pallidotomy and quality of life in patients with Parkinson's disease: an early study. Mov Disord . 2000; 15 65-70
- 51 Uitti R J, Wharen R E, Turk M F. Efficacy of levodopa therapy on motor function after posteroventral pallidotomy for Parkinson's disease. Neurology . 1998; 51 1755-1757
- 52 Kishore A, Turnbull I M, Snow B J. Efficacy, stability and predictors of outcome of pallidotomy for Parkinson's disease: six month follow-up with additional 1-year observations. Brain . 1997; 120 729-737
- 53 Koller W C, Pahwa R, Lyons K, Albanese A. Surgical treatment of Parkinson's disease. J Neurol Sci . 1999; 167 1-10
- 54 Ondo W G, Ben-Aire L, Jankovic J. Weight gain following unilateral pallidotomy in Parkinson's disease. Acta Neurol Scand . 2000; 101 79-84
- 55 Johnson K A, Cunnginton R, Bradshaw J L. Bimanual co-ordination in Parkinson's disease. Brain . 1998; 121 743-753
- 56 Schuurman P R, De Bie M A R, Speelman J D. Bilateral posteroventral pallidotomy in advanced Parkinson's disease in three patients. Mov Disord . 1997; 12 7552-7555
- 57 Hoehn M M, Yahr M D. Evaluation of the long term results of surgical therapy. In: Gillingham FJ, Donaldson IML, eds. Third Symposium on Parkinson's Disease
London: Livingstone 1969: 274-280
MissingFormLabel
- 58 Scott R, Gregory T, Hines N. Neuropsychological, neurological, and functional outcome following pallidotomy for Parkinson's disease: a consecutive series of eight simultaneous bilateral and twelve unilateral procedures. Brain . 1998; 121 659-675
- 59 Giller C A, Dewey R B, Ginsburg M I. Stereotactic pallidotomy and thalamotomy using individual variations of anatomic landmarks for localization. Neurosurgery . 1998; 42 56-62
- 60 Merello M, Nouzeilles M I, Kuzis G. Unilateral radiofrequency lesion versus electrostimulation of posteroventral pallidum: a prospective randomized comparison. Mov Disord . 1999; 14 50-56
- 61 Siegfried J, Compte P, Meier R. Intracerebral electrode implantation system. J Neurosurg . 1983; 59 356-359
- 62 Siegfried J, Rea G. Advances in neurostimulation devices. In: Plichina F, Broggi G, eds. Advanced Technology in Neurosurgery
Berlin: Springer 1988: 199-207
MissingFormLabel
- 63 Tasker R R, Organ L W, Hawrylshyn P. Investigation of the surgical target for alleviation of involuntary movement disorders. Appl Neurophysiol . 1982; 45 261-274
- 64 Benabid A L, Pollak P, Gao D. Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. J Neurosurg . 1996; 84 203-214
- 65 Blond S, Caparros-Lefebvre D, Parker F. Control of tremor and involuntary movement disorders by chronic stereotactic stimulation of the ventral intermediate thalamic nucleus. J Neurosurg . 1992; 77 62-68
- 66 Koller W, Pahwa R, Busenbark K. High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor. Ann Neurol . 1997; 42 292-299
- 67 Limousin P, Speelman J D, Gielsen F. Multicentre European study of thalamic stimulation in parkinsonian and essential tremor. J Neurol Neurosurg Psychiatry . 1999; 66 289-296
- 68 Ondo W, Jankovic J, Schwartz K. Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson's disease tremor. Neurology . 1998; 51 1063-1069
- 69 Schuurman P R, Bosch D A, Bossuyt P. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med . 2000; 342 461-468
- 70 Siegfried J, Lippitz B. Bilateral chronic electrostimulation of ventroposterolateral pallidum: a new therapeutic approach for alleviating all parkinsonian symptoms. Neurosurgery . 1994; 35 1126-1130
- 71 Volkman J, Sturm V, Weiss P. Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson's disease. Ann Neurol . 1998; 44 953-961
- 72 Ghika J, Villemure J G, Fankhauser H. Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa-responsive patients with Parkinson's disease with severe motor fluctuations: a 2-year follow-up review. J Neurosurg . 1998; 89 713-718
- 73 Benazzouz A, Piallat B, Ni G. Implication of the subthalamic nucleus in the pathophysiology and pathogenesis of Parkinson's disease. Cell Transplant . 2000; 9 215-221
- 74 Smith Y, Parent A. Neurons of the subthalamic nucleus in primates display glutamate but not GABA immunoreactivity. Brain Res . 1988; 453 353-356
- 75 Sellal F, Hirsch E, Lisovoski F. Contralateral disappearance of parkinsonian signs after subthalamic hematoma. Neurology . 1992; 42 255-256
- 76 Rodriguez M C, Obeso J A, Olanow C W. Subthalamic nucleus-mediated excitotoxicity in Parkinson's disease: a target for neuroprotection. Ann Neurol . 1998; S175-S188 (S175-S188)
- 77 Limousin P, Krack P, Pollak P. Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med . 1998; 339 1105-1111
- 78 Krack P, Pollak P, Limousin P. Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson's disease. Brain . 1998; 121 451-457
- 79 Houeto J L, Damier P, Bejjani P B. Subthalamic stimulation in Parkinson's disease. Arch Neurol . 2000; 57 461-465
- 80 Moro E, Scerrati M, Romito L MA. Chronic subthalamic nucleus stimulation reduced medication requirements in Parkinson's disease. Neurology . 1999; 53 85-90
- 81 Krack P, Pollak P, Limousin P. From off-period dystonia to peak-dose chorea: the clinical spectrum of varying subthalamic nucleus activity. Brain . 1999; 122 1133-1146
- 82 Kumar R, Lozano A M, Sime E. Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation. Neurology . 1999; 53 561-566
- 83 Krack P, Pollak P, Limousin P. Subthalamic nucleus stimulation and internal pallidal stimulation in young onset Parkinson's disease. Brain . 1998; 121 451-457
- 84 Kumar R, Lozano A M, Montgomery E. Pallidotomy and deep brain stimulation of the pallidum and subthalamic nucleus in advanced Parkinson's disease. Mov Disord . 1998; 13 73-82
- 85 Burchiel K J, Anderson V C, Favre J. Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson's disease: results of a randomized, blinded pilot study. Neurosurgery . 1999; 45 1375-1384
- 86 Ardouin C, Pillon B, Peiffer E. Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: a consecutive series of 62 patients. Ann Neurol . 1999; 46 217-223
- 87 Madrazo I, Drucker-Colin R, Diaz V. Open microsurgical autograft of adrenal medulla to right caudate nucleus in two patients with intractable Parkinson's disease. N Engl J Med . 1987; 316 831-834
- 88 Ahlskog J E, Kelly P I, van Heerden A J. Adrenal medullary transplantation into the brain for treatment of Parkinson's disease: clinical outcome and neurochemical studies. Mayo Clin Proc . 1990; 65 305-328
- 89 Apuzzo J L, Neal H, Waters C H. Utilization of unilateral and bilateral stereotactically placed adrenomedullary-striatal autografts in parkinsonian humans: rationale, techniques and observations. Neurosurgery . 1990; 26 746-757
- 90 Koller W C, Waxman M, Morantz R. Adrenal neural transplants in Parkinson's disease. Adv Neurol . 1990; 53 559-565
- 91 Olanow C W, Koller W C, Goetz C G. Autologous transplantation of adrenal medulla in Parkinson's disease. Arch Neurol . 1990; 47 1286-1289
- 92 Goetz C G, Stebbins G T, Klawans H L. United Parkinson Foundation neurotransplantation registry on adrenal medullary transplant: presurgical, and 1- and 2-year follow-up. Neurology . 1991; 41 1719-1722
- 93 Jankovic J, Grossman R, Goodman C. Clinical, biochemical, and neuropathologic findings following transplantation of adrenal medulla to the caudate nucleus for treatment of Parkinson's disease. Neurology . 1989; 39 1227-1234
- 94 Frank F, Sturiale C, Gaist C. Adrenal medulla autograft in a human brain for Parkinson's disease. Acta Neurochir (Wien) . 1988; 94 162-163
- 95 Hurtig H, Joyce J, Sladek J R. Post-mortem analysis of adrenal medulla-to-caudate autograft in a patient with Parkinson's disease. Ann Neurol . 1989; 25 607-614
- 96 Waters C H, Itabashi H H, Apuzzo M LJ. Adrenal to caudate transplantation: post mortem study. Mov Disord . 1990; 5 248-250
- 97 Kordower J H, Cochran E, Penn R. Putative chromaffin cell survival and enhanced host derived TH-fiber innervation following a functional adrenal medulla autograft for Parkinson's disease. Ann Neurol . 1991; 29 405-412
- 98 Hirsch E C, Duyckaerts C, Javoy-Agid F. Does adrenal graft enhance recovery of dopaminergic neurons in Parkinson's disease?. Ann Neurol . 1990; 27 676-682
- 99 Bjorklund A, Stenevi U, Schmidt R H. Intracerebral grafting of neuronal cell suspensions: I. Introduction and general methods of preparation. Acta Physiol Scand . 1983; 522 9-18
- 100 Perlow M, Freed W J, Hoffer B J. Brain grafts reduce motor abnormalities produced by destruction of nigro-striatal dopamine system. Science . 1979; 204 643-647
- 101 Clarkson E D, Freed C R. Development of fetal neural transplantation as a treatment for Parkinson's disease. Life Sci . 1999; 23 2427-2437
- 102 Lindvall O, Rehncrona S, Gustavii N. Fetal dopamine-rich mesencephalic grafts in Parkinson's disease. Lancet . 1988; 1483-1484
- 103 Mahalick T J, Finger T E, Stromberg I. Substantia nigra transplants into denervated striatum of the rat: ultrastructure of graft-host interconnections. J Comp Neurol . 1985; 240 60-70
- 104 Wuerthele S M, Freed W J, Olson L. Effects of dopamine agonists and antagonists on the electrical activity of substantia nigra neurons transplanted into the lateral ventricle of the rat. Exp Brain Res . 1981; 44 1-10
- 105 Schmidt R H, Ingvar M, Lindvall O. Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and [14C]-2-deoxy-D-glucose autoradiography. J Neurochem . 1982; 38 737-748
- 106 Brundin P, Bjorklund A. Survival, growth and function of dopaminergic neurons grafted to the brain. Prog Brain Res . 1987; 71 293-308
- 107 Sladek J R, Collier T C, Haber S N. Survival and growth of fetal catecholamine neurons transplanted into the primate brain. Brain Res Bull . 1986; 17 809-818
- 108 Bakay R AE, Barrow D L, Fiandca M S. Biochemical and behavioral correction of MPTP-like syndrome by fetal transplantation. Ann N Y Acad Sci . 1987; 495 623-640
- 109 Lindvall O. Update of fetal transplantation: the Swedish experience. Mov Disord . 1998; 83-87 (83-87)
- 110 Lindvall O. Neural transplantation: a hope for patients with Parkinson's disease. Neuroreport . 1997; 8 iii-x
- 111 Piccini P, Brooks D J, Bjorklund A. Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient. Nat Neurosci . 1999; 2 1137-1140
- 112 Lindvall O, Sawle G, Widner H. Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease. Ann Neurol . 1994; 35 172-180
- 113 Freeman T B, Olanow C W, Hauser R A. Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson's disease. Ann Neurol . 1995; 38 379-388
- 114 Kordower J H, Freeman T B, Snow B A. Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson's disease. N Engl J Med . 1995; 332 1118-1124
- 115 Kordower J H, Freeman T B, Olanow C W. Neuropathology of fetal nigral grafts in patients with Parkinson's disease. Mov Disord . 1998; 88-95 (88-95)
- 116 Hauser R A, Freeman T B, Snow B J. Long-term evaluation of bilateral fetal nigral transplantation in Parkinson's disease. Arch Neurol . 1999; 56 179-187
- 117 Wenning G K, Odin P, Morrish P. Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease. Ann Neurol . 1997; 42 95-107
- 118 Fahn S. Double-blind controlled trial of embryonic dopaminergic tissue transplants in advanced Parkinson's disease. Mov Disord . 2000; M114 (M114)
- 119 Greenley H T, Hamm T, Johnson R. The ethical use of human embryonic tissue in medicine. N Engl J Med . 1989; 320 1093-1096
- 120 Freeman T B, Wojak J, Brandeis L. Cross-species intracerebral grafting of embryonic swine dopaminergic neurons. Prog Brain Res . 1988; 78 473-477
- 121 Schumacher J M, Ellias S A, Palmer E P. Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology . 2000; 54 1042-1050
- 122 Subramanian R, Burnette B, Bakay R AE. Intrastriatal transplantation of human retinal pigmented epithelial cells attached to gelatin microcarriers (hRPE-GM) improved parkinsonian motor signs in hemiparkinsonian (HP) monkeys. Mov Disord . 1998; 13 268
- 123 Subramanian R, Bakay R AE, Cornfeldt M E. Blinded placebo-controlled trial to assess the effects of striatal transplantation of human retinal pigmented epithelial cells attached to microcarriers (hRPE-M) in parkinsonian monkeys. Parkinsonism Relat Disord . 1999; 5 S111
- 124 Chang C JG, Cornfeldt M L, Schweikert A W. Intracranial tolerability of SpheramineTM (gelatin microcarrier-bound human retinal pigment epithelial (hRPE) cells) and gelatin microcarriers in cynomolgus monkey. Soc Neurosci . 1999; 25 747