TY - JOUR
T1 - Central nervous system malformations induced by triamcinolone acetonide in nonhuman primates
T2 - Pathology
AU - Tarara, R. P.
AU - Cordy, D. R.
AU - Hendrickx, Andrew G
PY - 1989
Y1 - 1989
N2 - Triamcinolone acetonide (TAC) was administered to pregnant macaques (Macaca mulatta [15] and M. radiata [7]) during gestational days (GD) 23 to 41 using various dosing schedules. A daily dose of 10 mg/kg is ≅ 100 × the human dose equivalent. The brains of the fetuses and infants were studied grossly and histologically. All cases displayed either the mild form of the TAC‐induced syndrome (craniofacial dysmorphia, cranium bifidum occultum, meningocele, and mild distortion of the midbrain) or the more severe form (occipital encephalocele, hydrocephalus, severe distortion of the midbrain or midbrain “beaking,” shunting of cerebrospinal fluid, and craniofacial malformations). The dysmorphology was dose‐related, with severity increasing at higher doses or with increased numbers of treatments. Individual cases were assessed for the severity of the syndrome by comparison of like components between groups. The lesions observed were morphologically comparable to those described in spontaneous human cases; the TAC‐induced occipital encephaloceles were associated with brainstem and cerebellar abnormalities, and, with the less severe form of the syndrome, brainstem abnormalities were occasionally present, with occipital meningoceles. Controversy exists concerning the significance and temporal development of the midbrain changes. However, the associated alteration in aqueduct conformation may have been responsible for functional compromise and ensuing hydrocephalus.
AB - Triamcinolone acetonide (TAC) was administered to pregnant macaques (Macaca mulatta [15] and M. radiata [7]) during gestational days (GD) 23 to 41 using various dosing schedules. A daily dose of 10 mg/kg is ≅ 100 × the human dose equivalent. The brains of the fetuses and infants were studied grossly and histologically. All cases displayed either the mild form of the TAC‐induced syndrome (craniofacial dysmorphia, cranium bifidum occultum, meningocele, and mild distortion of the midbrain) or the more severe form (occipital encephalocele, hydrocephalus, severe distortion of the midbrain or midbrain “beaking,” shunting of cerebrospinal fluid, and craniofacial malformations). The dysmorphology was dose‐related, with severity increasing at higher doses or with increased numbers of treatments. Individual cases were assessed for the severity of the syndrome by comparison of like components between groups. The lesions observed were morphologically comparable to those described in spontaneous human cases; the TAC‐induced occipital encephaloceles were associated with brainstem and cerebellar abnormalities, and, with the less severe form of the syndrome, brainstem abnormalities were occasionally present, with occipital meningoceles. Controversy exists concerning the significance and temporal development of the midbrain changes. However, the associated alteration in aqueduct conformation may have been responsible for functional compromise and ensuing hydrocephalus.
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U2 - 10.1002/tera.1420390109
DO - 10.1002/tera.1420390109
M3 - Article
C2 - 2718142
AN - SCOPUS:0024532154
VL - 39
SP - 75
EP - 84
JO - Teratology
JF - Teratology
SN - 1542-0752
IS - 1
ER -