Neuropathic arthrogryposis multiplex congenita and intrauterine ischemia of anterior horn cells: a hypothesis.
Three patients with multiple articular deformities due to arthrogryposis multiplex congenita (AMC) are presented. All had severe thalamic and tegmental degenerations with glial scars and shrunken ferruginated neurons; one had also unilateral porencephaly and polymicrogyri. The character and the pattern of the lesions were highly suggestive of in-utero hypotensive/ischemic insult. Marked attenuations of anterior spinal roots were mostly seen in the lumbosacral and cervical enlargements, where anterior horn cell loss and ferrugination were most severe. The changes in the anterior horns were situated peripherally, a distribution corresponding to the terminal ramifications of the sulcal (central) branches of the anterior spinal artery, an area known for its susceptibility to ischemia, especially in children. The changes in the brains and spinal cords could reasonably be explained on the basis of intra-uterine perfusion failure in early stages of fetal development. This assumption was supported by the fact that all three patients were subjected to unfavorable environmental factors during gestation. The first was the twin of a macerated infant; their entangled umbilical cords might have caused differential placental perfusion resulting in partial ischemia in the twin with AMC and severe ischemia in the other accounting for its early demise. The second patient had a single functional umbilical artery, a condition frequently associated with developmental anomalies. The third was born to a mother whose pregnancy was complicated by heavy substance abuse. Ischemic myelopathy during a critical phase of CNS developmental and muscle innervation is proposed as a cause of some cases of neuropathic AMC. Placental circulatory failure should be considered in the pathogenesis of AMC in such cases.
Horoupian
D S
DS
Department of Pathology (Neuropathology), Stanford University Medical Center, CA 94305.
Yoon
J J
JJ
D001176:Arthrogryposis / Q000209:etiology* / Q000473:pathology; D001921:Brain / Q000002:abnormalities*; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D013577:Syndrome