Anatomic Variation of Rami Communicantes in the Upper Thoracic Sympathetic Chain: A Human Cadaveric Study.

BACKGROUND: Hyperhidrosis is secondary to over activation of the sympathetic nervous system and surgical sympathectomy is the treatment of choice when other modalities have failed. This study investigated anatomic variation in the upper thoracic sympathetic chain and associated rami communicantes among cadaveric specimens. It considers the implications of these findings on surgical techniques to treat hyperhidrosis. METHODS: The upper 4 thoracic sympathetic ganglia, intercostal nerves, and connecting rami were dissected, measured and mapped in 40 sides of 20 adult human cadavers. Ganglia location was recorded. The incidence, orientation, and distance travelled by rami communicantes was compared across different ganglionic levels and between sides. RESULTS: The percentage of ganglia located below their associated intercostal space was 6.25% with stellate ganglions present in 70% of specimens and Kuntz fibers noted in 40%. There was a stepwise reduction in incidence of rami from superior to inferior placed ganglia. The number of rami identified across all levels was significantly greater on the right (P = 0.03). The horizontal distance between the sympathetic chain and union of the rami on the intercostal nerves was significantly greater on the right across all levels (P = 0.04). CONCLUSIONS: There was substantial variation in the rami communicantes across the upper 4 ganglia and between right and left sides. Consideration of this variation should be given when planning surgical sympathectomy for hyperhidrosis particularly to avoid symptom recurrence.

FRS2 alpha 2F/2F mice lack carotid body and exhibit abnormalities of the superior cervical sympathetic ganglion and carotid sinus nerve.

The docking protein FRS2 alpha is an important mediator of fibroblast growth factor (FGF)-induced signal transduction, and functions by linking FGF receptors (FGFRs) to a variety of intracellular signaling pathways. We show that the carotid body is absent in FRS2 alpha(2F/2F) mice, in which the Shp2-binding sites of FRS2 alpha are disrupted. We also show that the carotid body rudiment is not formed in the wall of the third arch artery in mutant embryos. In wild-type mice, the superior cervical ganglion of the sympathetic trunk connects to the carotid body in the carotid bifurcation region, and extends thick nerve bundles into the carotid body. In FRS2 alpha(2F/2F) mice, the superior cervical ganglion was present in the lower cervical region as an elongated feature, but failed to undergo cranio-ventral migration. In addition, few neuronal processes extended from the ganglion into the carotid bifurcation region. The number of carotid sinus nerve fibers that reached the carotid bifurcation region was markedly decreased, and baroreceptor fibers belonging to the glossopharyngeal nerve were absent from the basal part of the internal carotid artery in FRS2 alpha(2F/2F) mutant mice. In some of the mutant mice (5 out of 14), baroreceptors and some glomus cells were distributed in the wall of the common carotid artery, onto which the sympathetic ganglion abutted. We propose that the sympathetic ganglion provides glomus cell precursors into the third arch artery derivative in the presence of sensory fibers of the glossopharyngeal nerve.

[Superior cervical ganglion: an anatomical variant. Are variations of the cranial carotid artery a risk factor for accidental intravascular injection?]. / Ganglion cervicale superius: eine anatomische Besonderheit. Variationen der A. carotis interna als Risiko einer akzidentellen intravasalen Injektion?

A variation of the cranial carotid artery is demonstrated in an anatomical specimen revealing possible complications of ganglionic local opioid analgesia at the superior cervical ganglion. Located in the area of the puncture site, a loop of the aberrant carotid artery adheres closely to the pharyngeal wall in the medial position, shortening the distance between the arterial lumen and the oral cavity to 5 mm. With an incidence of 25%, an aberrant carotid artery could possibly facilitate an accidental intravascular injection during ganglionic local opioid application at the superior cervical ganglion.

Abnormal sympathoadrenal development and systemic hypotension in PHD3-/- mice.

Cell culture studies have implicated the oxygen-sensitive hypoxia-inducible factor (HIF) prolyl hydroxylase PHD3 in the regulation of neuronal apoptosis. To better understand this function in vivo, we have created PHD3(-/-) mice and analyzed the neuronal phenotype. Reduced apoptosis in superior cervical ganglion (SCG) neurons cultured from PHD3(-/-) mice is associated with an increase in the number of cells in the SCG, as well as in the adrenal medulla and carotid body. Genetic analysis by intercrossing PHD3(-/-) mice with HIF-1a(+/-) and HIF-2a(+/-) mice demonstrated an interaction with HIF-2alpha but not HIF-1alpha, supporting the nonredundant involvement of a PHD3-HIF-2alpha pathway in the regulation of sympathoadrenal development. Despite the increased number of cells, the sympathoadrenal system appeared hypofunctional in PHD3(-/-) mice, with reduced target tissue innervation, adrenal medullary secretory capacity, sympathoadrenal responses, and systemic blood pressure. These observations suggest that the role of PHD3 in sympathoadrenal development extends beyond simple control of cell survival and organ mass, with functional PHD3 being required for proper anatomical and physiological integrity of the system. Perturbation of this interface between developmental and adaptive signaling by hypoxic, metabolic, or other stresses could have important effects on key sympathoadrenal functions, such as blood pressure regulation.

Hirschsprung's disease: genetic mutations in mice and men.

Hirschsprung's disease is a neuronal dysplasia of the hindgut, characterised by a loss of neurones, which affects about 1 in 5000 live births. Genetic factors have been implicated in the aetiology of this disease in about 20% of cases and a dominant pattern of inheritance has been revealed in several families. The pathogenesis of the aganglionosis is often attributed to a failure of migration of neural crest cells, although this has not been proven. Recently, mutations in a developmentally regulated receptor tyrosine kinase gene, ret, and mutations in the endothelin receptor-B gene (ENDR-B) have both been linked to familial Hirschsprung's disease in humans. Moreover, certain mutant mouse strains--namely piebald lethal and lethal spotted--exhibit striking similarities to the human condition. The mutation which gives rise to piebald lethal has now been found to be in the ENDR-B gene, and the mutation associated with lethal spotted occurs in the gene for endothelin-3 (ET-3), a ligand for ENDR-B. Two transgenic mouse lines have been developed which also reflect the human disease: ret-k-, which has a loss of function mutation of the ret gene, and ENDR-B null. In addition, the introduction of a Lac-Z reporter gene into neural crest cells of aganglionic mice has made it possible to study directly the fate of enteric neuroblasts which are affected by "Hirschsprung's-like" mutations. Here, we review the possible roles of RET and endothelin in the normal development of the enteric nervous system, and the significance of their mutated forms in the pathogenesis of familial aganglionosis. This review focuses on recent advances in our understanding of the genetic basis of the lesions which have been implicated in congenital forms of Hirschsprung's disease. Disruption of these genes in the mouse, either by transgenic "knockout" approaches or in mutant mouse lines, offers the prospect of greater understanding of both the cellular and developmental bases of the human disease.