1. Pollock A, Baer G, Pomeroy V, Langhorne P. Physiotherapy treatment ap- 10. Khadilkar A, Phillips K, Jean N, Lamothe C, Milne S, Sarnecka J. Ottawa Panel
proaches for the recovery of postural control and lower limb function following
evidence-based clinical practice guidelines for post-stroke rehabilitation. Top Stroke
stroke. Cochrane Database Syst Rev. 2003;(2):CD001920. 2. Pomeroy VM, King L, Pollock A, Baily-Hallam A, Langhorne P. Electrostimu- 11. Gensini GF, Zaninelli A, Bignamini AA, et al. Italian Guidelines for Stroke Pre-
lation for promoting recovery of movement or functional ability after stroke. Coch-vention and Management. Milan, Italy: Hyperphar Group SpA; 2005. rane Database Syst Rev. 2006;(2):CD003241. 12. Hesse S, Hummelheim H, Liepert J, Nelles G. Motorische Rehabilitation nach 3. Moseley AM, Stark A, Cameron ID, Pollock A. Treadmill training and body weight
Schlaganfall. In: Diener HC, ed. Leitlinien fur Diagnostik und Therapie in der Neu-
support for walking after stroke. Cochrane Database Syst Rev. 2005;(4):CD002840. rologie. Stuttgart, Germany: Thieme; 2005. 4. Paci M. Physiotherapy based on the Bobath concept for adults with post- 13. Scheidtmann K, Fries W, Muller F, Koenig E. Effect of levodopa in combina-
stroke hemiplegia: a review of effectiveness studies. J Rehabil Med. 2003;35:
tion with physiotherapy on functional motor recovery after stroke: a prospective,
randomised, double-blind study. Lancet. 2001;358:787-790. 5. Zorowitz RD, Gross E, Polinski DM. The stroke survivor. Disabil Rehabil. 2002; 14. Horn SD, DeJong G, Smout RJ, Gassaway J, James R, Conroy B. Stroke reha-
bilitation patients, practice, and outcomes: is earlier and more aggressive therapy
6. Wolf SL, Winstein CJ, Miller JP, et al; for the EXCITE Investigators. Effect of
better? Arch Phys Med Rehabil. 2005;86(12 suppl 2):S101-S114.
constraint-induced movement therapy on upper extremity function 3 to 9 months
15. Liepert J, Bauder H, Miltner WH, Taub E, Weiller C. Treatment-induced cor-
after stroke: the EXCITE randomized clinical trial. JAMA. 2006;296:2095-2104.
tical reorganization after stroke in humans. Stroke. 2000;31:1210-1216. 7. Taub E, Uswatte G. Constraint-induced movement therapy: answers and ques- 16. Schaechter JD. Motor rehabilitation and brain plasticity after hemiparetic stroke.
tions after two decades of research. NeuroRehabilitation. 2006;21:93-95. Prog Neurobiol. 2004;73:61-72. 8. Hamzei F, Liepert J, Dettmers C, Weiller C, Rijntjes M. Two different reorga- 17. Luft AR, McCombe-Waller S, Whitall J, et al. Repetitive bilateral arm training
nization patterns after rehabilitative therapy: an exploratory study with fMRI and
and motor cortex activation in chronic stroke: a randomized controlled trial. JAMA.
TMS. Neuroimage. 2006;31:710-720. 9. Luft AR, Waller S, Forrester L, et al. Lesion location alters brain activation in 18. Bobath B. Adult Hemiplegia: Evaluation and Treatment. London, England:
chronically impaired stroke survivors. Neuroimage. 2004;21:924-935. Sudden Infant Death Syndrome Is Serotonin the Key Factor?
in SIDS cases and begins to address the sex disparity in SIDSincidence. Recognizing that 5-HT influences a broad range
of physiological systems including the regulation of breath-
EUROPATHOLOGICAL STUDIES HAVE IDENTIFIED A KEYrole for the serotonin (5-hydroxytryptamine
ing, the cardiovascular system, temperature, and the sleep-
[5-HT]) pathways in sudden infant death syn-
wake cycle, the study by Paterson et al4 extends the avail-
drome (SIDS). Panigrahy et al1 reported a de-
able literature in support of the underlying hypothesis that
crease in 5-HT receptor binding in the arcuate nucleus, raphe´
SIDS is the result of 5-HT–mediated dysregulation of the au-
obscurus, and other medullary regions that contain 5-HT
cell bodies in SIDS cases in the United States. Similarly, Ozawa
While the published neuropathological data are derived
and Okado2 reported a decrease in 5-HT receptor binding
from elegant studies, African American infants are one key
in the dorsal nucleus of the vagus, solitary nucleus, and ven-
group consistently underrepresented. Despite decreases in
trolateral medulla in SIDS cases in Japan. Subsequently, Kin-
the SIDS incidence in the United States with aggressive
ney et al3 confirmed their prior observations of altered 5-HT
Back to Sleep educational programs,5 the final 2003
receptor binding in medullary regions in Native American
National Vital Statistics indicate a SIDS rate of 0.424 per
Indians, a group at high risk for SIDS.
1000 live births for white infants but a rate of 1.152 per
In this issue of JAMA, Paterson and colleagues4 report that
1000 live births for African American infants.6 These data
“SIDS cases had a significantly higher number and density
reflect a 2.7-fold higher incidence among African American
of 5-HT neurons . . . and a significantly lower density of
infants compared with white infants. Although this limita-
tion of existing studies should not detract from the impor-
1A receptor binding sites . . . in regions of the medulla
involved in homeostatic function compared with controls”
tance of the results, and the study describing Native Ameri-
and that “the density of [5-HT transporter] binding rela-
can infants3 does represent an at-risk study population, it
tive to the number of 5-HT neurons in the medulla was sig-
suggests a need for expansion of the populations for future
nificantly lower in SIDS cases compared with controls.” Fur-
neuropathological studies from the primarily white and
ther, Paterson et al4 demonstrate that male infants who
Hispanic infants recruited from San Diego1,4 to those who
more specifically represent the ethnicities of those who suc-
sity in the raphe´ obscurus compared with female infants.
Taken together, the evidence strongly supports extensiveabnormalities in the 5-HT neuropathology of the medulla
Author Affiliation: Department of Pediatrics, Pediatric Respiratory Medicine, Rush University Medical Center, Chicago, Ill. Corresponding Author: Debra Ellyn Weese-Mayer, MD, Department of Pediat- See also p 2124.
rics, Pediatric Respiratory Medicine, Rush University Medical Center, 1653 W Con-gress Pkwy, Chicago, IL 60612 (firstname.lastname@example.org).
2006 American Medical Association. All rights reserved.
(Reprinted) JAMA, November 1, 2006—Vol 296, No. 17 2143
One solution is for medical examiners in regions with more
bedding materials, overheating, and exposure to prenatal
representative ethnicity for SIDS to join forces in provid-
and postnatal cigarette smoke should be avoided. Despite
ing autopsy specimens for neuropathological researchers.
remarkable progress made nationally in compliance with
An alternative solution is to encourage development of young
these known modifiable risk factors for SIDS, it is discour-
neuropathological investigators (particularly in universi-
aging that 65% of the infants who succumbed to SIDS in
ties serving ethnically diverse populations, including Afri-
the study by Paterson et al were in the prone or side sleep-
can Americans) to pursue the study of SIDS in their own
ing position at the time of death. These results emphasize
laboratories. In so doing, the next generation of neuropatho-
the critical need for reintroduction of the Back to Sleep cam-
logical scientists studying SIDS will be secured, and infants
paign to educate parents and caretakers of young infants.
more representative of the SIDS population can be in-
Alternatively, it may be time to introduce more innovative
interventions that focus on the different ethnic groups af-
Another key concern is the limited sample sizes for SIDS
cases and controls in the published neuropathological stud-
While the neuropathological studies in SIDS are provid-
ies. The opportunity to perform these important studies is
ing remarkable insight into the underlying mechanisms in
dependent on access to the neuropathological tissue. That
the 5-HT pathways, identification of the definitive cause for
access has been made possible, in part, under a California
SIDS will necessitate an expanded network of scientists and
law7 that renders it unnecessary to obtain informed con-
families working together toward the shared goal. They can
sent from individual parents if tissue samples from their child
join forces to influence legislation in their own states to rep-
are to be used for research on sudden and unexpected in-
licate the success of the California program. Likewise, cli-
fant death. This statute was visionary and has allowed for
nicians and researchers can gently inform parents who have
remarkable progress in understanding the neuropathology
lost an infant to SIDS about autopsy and the opportunity
of SIDS. If it were possible for more states to follow the lead
for their lost infant to contribute to the further understand-
of California, sample size and ethnic diversity for these es-
ing of SIDS. With 2162 infants dying from SIDS in the United
sential SIDS studies would be expanded, controls could be
States in 2003,6 there is no time to lose in determining if
matched in a 1:1 ratio with SIDS cases, and the desperately
serotonin is the key factor in the pathophysiology of SIDS.
sought answers as to why SIDS continues to occur mightbe elucidated at a faster pace. Financial Disclosures: None reported.
Currently, controls used in the neuropathological stud-
ies have typically died from a preceding illness or disease. Because of the possibility that current controls had an un-
derlying susceptibility that increased their vulnerability to
1. Panigrahy A, Filiano J, Sleeper LA, et al. Decreased serotonergic receptor bind-
that illness, to death, or both, or that sequelae from the ill-
ing in rhombic lip-derived regions of the medulla oblongata in the sudden infantdeath syndrome. J Neuropathol Exp Neurol. 2000;59:377-384.
ness might affect their neuropathological findings, it seems
2. Ozawa Y, Okado N. Alteration of serotonergic receptors in the brainstems of
possible that the reported controls may not reflect the “nor-
human patients with respiratory disorders. Neuropediatrics. 2002;33:142-149. 3. Kinney HC, Randall LL, Sleeper LA, et al. Serotonergic brainstem abnormalities
mal” condition. By broadening geographic sources, more con-
in Northern Plains Indians with the sudden infant death syndrome. J Neuropathol
trols who died from trauma or other unintended events with-
Exp Neurol. 2003;62:1178-1191. 4. Paterson DS, Trachtenberg FL, Thompson EG, et al. Multiple serotonergic brain-
out antecedent illness may be included.
stem abnormalities in sudden infant death syndrome. JAMA. 2006;296:2124-2132.
As Paterson et al4 clearly explain, data on infants in their
5. American Academy of Pediatrics Task Force on Sudden Infant Death Syndrome. The changing concept of sudden infant death syndrome: diagnostic coding shifts,
study were collected after the successful implementation of
controversies regarding the sleep environment, and new variables to consider in
the Back to Sleep message recommending that infants
reducing risk. Pediatrics. 2005;116:1245-1255.
younger than 1 year should be placed on their backs to sleep,
6. Hoyert DL, Heron MP, Murphy SL, Kung H-C. Death: final data from 2003. Natl Vital Stat Rep. 2006;54:99.
that they should be sleeping on firm surfaces, and that soft
7. California Law Chapter 955, Statutes of 1989 (SB 1069). 2144 JAMA, November 1, 2006—Vol 296, No. 17 (Reprinted)
2006 American Medical Association. All rights reserved.
Résumé de l’interview de B. Galliot : Définition cellules souches: 2 critères : • Self-renewal = Capables de se renouveler elles-mêmes de façon indéfinie. • Capable de produire des divisions asymétriques : une pour auto-reproduction du pool de cellules souches et l’autre qui rentre dans un chemin de différenciation. Autre critère : • Cellules souches (totipotente