Parkinson’s disease is a degenerative disease of the dopaminergic cells of the brain with symptoms including resting tremor, rigidity, and bradykinesia. In an effort to modify the disability of advanced Parkinson’s disease, embryonic mesencephalic tissue containing dopamine-producing cells is implanted into the caudate and putamen of the candidate’s brain.

Investigational/Not Medically Necessary:

Adrenal-to-brain transplantation with autograft or fetal allograft is considered investigational/not medically necessary in all cases.

Fetal mesencephalic transplantation for the treatment of Parkinson's disease is considered investigational/not medically necessary.

Transplantation with fetal xenografts (i.e., from pigs or other animals) for the treatment of Parkinson's disease is considered investigational/not medically necessary.
 

At this time, the medical literature regarding adrenal-to-brain transplantation for the treatment of Parkinson’s disease is limited to the description of uncontrolled, short-term studies with small sample sizes or case studies.  Although some of these studies did report finding significant clinical improvements, unreasonably high morbidity and mortality rates are frequent.  A few pathologic reports on adrenal-to-brain recipients demonstrated very few to no surviving transplanted cells after 6 months to a year following surgery.  Due to the lack of long term outcomes data for large controlled randomized trials and reports of high rates of complications and death in the existing literature, in 1999 the American Academy of Neurology came to the conclusion that adrenal-to-brain transplantation for the treatment of Parkinson’s disease should be considered unacceptable for safety reasons.  We see no reason to contradict this position and consider this procedure investigational.

The evidence for fetal mesencephalic transplantation is more promising than that for adrenal-to brain procedures.  However, the existing body of literature is still inadequate to allow conclusions regarding this procedure.  Concerns related to small sample sizes and a limited number of controlled trials are joined with a wide array of methodological issues with the procedure itself.

The medical literature currently describes several different surgical approaches, either open or stereotactic, and bilateral vs. unilateral, along with several different tissue preparation methods, variation in the number of transplants, inclusion or exclusion of postoperative immunosuppressive therapy, and the type of screening used for tissue donors.  Concerns about methodology aside, the existing evidence for this type of procedure demonstrates low morbidity and mortality, significant improvements in short- and long-term physical symptoms, and graft viability and function is maintained. Although this type of treatment shows promise, with such a wide range of methods available and low level of evidence to support each, there is inadequate support for any one method at this time.

With concerns regarding the use of embryonic tissues at the center of an ethical and political debate, it is unlikely that any large-scale use of fetal mesencephalic transplantation will be forthcoming.  In response to such concerns, investigations into the use of porcine fetal mesencephalic transplantation are being conducted. While similar methodological issues exist as with human fetal transplantation, fewer ethical concerns make this type of procedure more widely accepted.  At this time, only a few small clinical trials have been described in the literature, but with some promising results. Further randomized controlled studies must be conducted before for this type of therapy may be adequately evaluated for use in the clinical setting.

Parkinson’s disease is a progressive, disabling disease caused by degeneration of cells in a part of the brain called the substantia nigra that produces dopamine, a brain chemical critical for movement of the body.  Approximately 500,000 people in the U.S. are believed to suffer from Parkinson’s disease, with about 50,000 new cased diagnosed annually. 

The disease usually begins as a slight tremor in one limb on one side of the body and slowly progresses to affect other parts of the body causing slow movement, the inability to move, rigid limbs, stooped posture and a range of mental symptoms such as personality changes, depression, inability to sleep, speech impairments and others.

At this time there is no cure for Parkinson’s disease.  Current accepted treatment for this disease involves drug therapy for mild to moderate symptoms and surgical procedures such as pallidotomy and electrical deep brain stimulation for severe cases.  However none of these treatments correct the underlying problem of nerve cell degeneration so the disease continues to progress.

Several techniques have been proposed for the treatment of the underlying cause of Parkinson’s disease in which tissue or cells from other sources are transplanted onto the patient's brain at the location where cell degeneration is occurring or in nearby areas. Theoretically, the transplanted cells are supposed to take the place of the dysfunctional brain cells by producing dopamine, thus improving the signs and symptoms of Parkinson’s disease. 

The transplantation of tissue from the adrenal glands, specifically adrenal medullary tissue, to a portion of the brain called the corpus striatum, called adrenal-to-brain transplantation, is intended to improve the motor and postural dysfunctions of Parkinson's disease. Adrenal-to-brain transplantation can involve either an autograft from the patient themselves or an allograft from an aborted fetus. When done with the patient’s own adrenal tissue, a complicated double surgery, one to remove the adrenal tissue, and one to transplant it into the brain, is required.

Another type of transplant for Parkinson’s disease, fetal mesencephalic transplantation, involves a surgical procedure to implant tissue harvested from fetal brains, specifically mesencephalic tissue, into portions of the patient’s brain known as the caudate and putamen areas. 

Finally, surgery to transplant brain tissue from fetal pigs into the brains of patients with Parkinson’s disease has also been attempted. The goal of this procedure, as with the other procedures described, is to implant dopamine-producing cells into the brain, alleviating the symptoms of the condition.

Autograft: the process of taking tissue from one part of the body and transplanting it into another part of the body with the goal of treating some specific disease or condition

Fetal allograft: the process of taking tissue or cells from an aborted fetus and transplanting it into the body of a patient with the goal of treating some specific disease or condition

Mesencephalic: pertaining to the mid-section of the brain

Xenograft: the process of taking tissues from another species, such as pigs, transplanting it into the body of a human patient with the goal of treating some specific disease or condition

The following codes for treatments and procedures applicable to this policy are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage or these services at it applies to an individual member.

When services are Investigational/Not Medically Necessary:

HCPCS

ICD-9 Diagnosis

Peer Reviewed Publications:

1. Bhattacharya N, Chetri MK, Mukherjee KL, et al. Can human fetal cortical brain tissue transplant (up to 20 weeks) sustain its metabolic and oxygen requirements in a heterotopic site outside the brain? A study of 12 volunteers with Parkinson's disease. Clin Exp Obstet Gynecol.  2002; 29(4):259-266.
2. Drucker-Colin R, Verdugo-Diaz L. Cell transplantation for Parkinson's disease: present status. Cell Mol Neurobiol. 2004; 24(3):301-316. 
3. Fillmore HL, Holloway KL, Gillies GT. Cell replacement efforts to repair neuronal injury: a potential paradigm for the treatment of Parkinson's disease. NeuroRehabilitation. 2005; 20(3):233-242.
4. Fink JS, Schumacher JM, Ellias SL, et al. Porcine xenografts in Parkinson’s disease and Huntington’s disease patients: Preliminary results. Cell Transplantation. 2000; 9(2):272-278.
5. Freed CT, Greene PE, Breeze RE, et al.  Transplantation of embryonic dopamine neurons for severe Parkinson’s disease.  N Engl J Med. 2001; 344(10):710-719.
6. Goetz CG, Olanow CW, Koller WC, et al. Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson's disease. N Engl J Med.1989; 320(6):337-341.
7. Goetz CG, Stebbins GT, Klawans HL, et al. United Parkinson Foundation Neurotransplantation Registry on adrenal medullary transplants: presurgical, and 1- and 2-year follow-up. Neurology. 1991; 41(11):1719-1722.
8. Jankovic J. An update on the treatment of Parkinson's disease. Mt Sinai J Med. 2006; 73(4):682-9.
9. Kopyov OV, Jacques D, Lieberman A, et al. Clinical study of mesencephalic intracerebral transplant for the treatment of Parkinson’s disease. Cell Transplant. 1996; 5(2):327-337.
10. Kopyov OV, Jacques D, Liberman A. Outcome of intrastriatial fetal mesencephalic grafts for Parkinson’s patients is directly related to the volume of grafted tissue. Exp Neurol. 1997; 146(2):536-545.
11. Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature. 2006; 441(7097):1094-1096.
12. Lopez-Lozano JJ, Bravo G, Abascal J. Grafting of perfused adrenal medullary tissue into the caudate nucleus of patients with Parkinson's disease. Clinica Puerta de Hierro Neural Transplantation Group. J Neurosurg. 1991; 75(2):234-243.
13. Ma Y, Feigen A, Dhawan V, et al. Dyskinesia after fetal cell transplantation for parkinsonism: A PET study.Ann Neurol. 2002; 52(5):628-634.
14. Schumacher JM, Ellias SL, Palmer EP, et al. Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology. 2000; 54(5):1042-1050.
15. Schwarz J, Schwarz SC, Storch A. Developmental perspectives on human midbrain-derived neural stem cells. Neurodegener Dis. 2006; 3(1-2):45-49.
16. Waxman MJ, Morantz RA, Koller WC, et al. High incidence of cardiopulmonary complications associated with implantation of adrenal medullary tissue into the caudate nucleus in patients with advanced neurologic disease. Crit Care Med. 1991; 19(2):181-186.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. Diagnosis and Treatment of Parkinson’s Disease: A Systematic Review of the Literature. Evidence Report/Technology Assessment Number 57. 2003. Available at:  http://www.ahrq.gov/downloads/pub/evidence/pdf/parkinsons/parkinsons.pdf. Accessed on December 19, 2006.
2. Blue Cross and Blue Shield Association.  Fetal mesencephalic transplantation for the treatment of Parkinson’s disease. TEC Assessment, 1995; 10(1).
3. Blue Cross and Blue Shield Association.  Embryonic mesencephalic transplantation for the treatment of Parkinson’s disease. TEC Assessment, 2001; 16(8).
4. Hallet M, Litvan I.  Evaluation of Surgery for Parkinson’s disease: A report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology.  Neurology.  1999; 53(9):1910-1921.
5. Hayes, Inc. Hayes Medical Technology Directory. Embryonic/Fetal Cell Transplantation for Parkinson’s Disease. January 2005. Search updated January 5, 2006.

1. National Library of Medicine. Medical Encyclopedia: Parkinson’s disease. Available at:  http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html.  Accessed on December 19, 2006.  
2. The National Parkinson Foundation. Available at:  www.parkinson.org.  Accessed on December 19, 2006.

Adrenal-to-Brain Transplantation
Fetal Mesencephalic Transplantation
Fetal Tissue Transplant
Parkinson's Disease Surgery
Xenograft
 

Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member's contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by an means, electronic, mechanical, photocopying, or otherwise, without permission from the health plan.

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