Cerebral vasospasm patterns following aneurysmal subarachnoid hemorrhage: an angiographic study comparing coils with clips.

BACKGROUND AND PURPOSE: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) results in significant morbidity due to ischemia. Subarachnoid hematoma evacuation during aneurysm clipping reduces the incidence of vasospasm. However, studies comparing endovascular coiling with open clipping have reported similar rates of spasm. We addressed the question of how coiling produces similar (if not less) vasospasm without the benefit of clot evacuation by evaluating vasospasm patterns among patients with aSAH. We hypothesize that cerebrospinal fluid (CSF) circulation plays a major role in clearing blood breakdown products, and that coiling may preserve CSF flow in the subarachnoid space. METHODS: A retrospective chart review identified 36 (18 coiled/18 clipped) patients with aSAH who developed angiographic vasospasm. The degree of spasm was quantified using an ordinal scale from 0 (none) to 5 (severe) for 26 anatomic vessel segments evaluated on 164 successive angiograms. Statistical analysis was performed using the Fisher exact test for proportions and the Wilcoxon and Student t tests on ordinal/continuous measures. Quadratic regression was also used as a model for spasm activity versus post-bleed days. RESULTS: In both the coiling and clipping groups the most severely spastic vessels were located adjacent to aneurysm rupture. Perianeurysmal spasm affected all subjects. However, whereas spasm remained largely confined in patients treated by clipping, those who underwent coiling developed stepwise progression distally over time. The distal vasospasm severity scores were higher among subjects treated by coiling, particularly in the most dependent regions of the subarachnoid space. CONCLUSIONS: Patients with aSAH treated by endovascular coiling and surgical clipping demonstrate distinct vasospasm patterns. While both initially exhibit perianeurysmal spasm, patients treated by coiling go on to develop stepwise progression distally over time. This finding may reflect dispersion of blood breakdown products along preserved CSF egress pathways in patients treated by endovascular coiling.

Pacinian corpuscle development involves multiple Trk signaling pathways.

The development of crural Pacinian corpuscles was explored in neonatal mutant mice lacking nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) or neurotrophin-4 (NT4), or their cognate Trk receptors. Deficits of the corpuscles and their afferents were greatest in NT3, less in BDNF, and least in NT4 null mice. Deletion of NGF or p75(NTR) genes had little or no impact. No Pacinian corpuscles were present in NT3;BDNF and NT3;NT4 double or NT3;BDNF;NT4 triple null mice. Deficits were larger in NT3 than TrkC mutants and were comparable to deficits observed in TrkB or TrkA mutants. Afferents of all corpuscles coexpressed TrkA and TrkB receptors, and some afferents coexpressed all three Trk receptors. Our results suggest that multiple neurotrophins, in particular NT3, regulate the density of crural Pacinian corpuscles, most likely by regulating the survival of sensory neurons. In addition, NT3/TrkB and/or NT3/TrkA signaling plays a greater role than NT3/TrkC signaling in afferents to developing Pacinian corpuscles.

Pluripotent neural crest stem cells in the adult hair follicle.

We report the presence of pluripotent neural crest stem cells in the adult mammalian hair follicle. Numerous neural crest cells reside in the outer root sheath from the bulge to the matrix at the base of the follicle. Bulge explants from adult mouse whisker follicles yield migratory neural crest cells, which in clonal culture form colonies consisting of over a thousand cells. Clones contain neurons, smooth muscle cells, rare Schwann cells and melanocytes, demonstrating pluripotency of the clone-forming cell. Targeted differentiation into Schwann cells and chondrocytes was achieved with neuregulin-1 and bone morphogenetic protein-2, respectively. Serial cloning in vitro demonstrated self-renewal capability. Together, the data show that the adult mouse whisker follicle contains pluripotent neural crest stem cells, termed epidermal neural crest cells (eNCSC). eNCSC are promising candidates for diverse cell therapy paradigms because of their high degree of inherent plasticity and due to their easy accessibility in the skin.

Formation of supernumerary muscle spindles at the expense of Golgi tendon organs in ER81-deficient mice.

ER81, a member of the ETS family of transcription factors, is essential for the formation of connections between sensory and motor neurons in the spinal cord. Mice lacking Er81 genes exhibit reduced monosynaptic sensory-motoneuron connectivity in response to muscle nerve stimulation. Proximal muscle nerve stimulation elicits fewer monosynaptic potentials than stimulation of distal nerves in hindlimbs, a deficit that is paralleled by a paucity of muscle spindles in proximal muscles (Arber et al., 2000). We examined whether a presence of spindles innervated by afferents in distal muscles correlated with the increased preservation of monosynaptic sensory-motor potentials in distal muscle nerves. Not only were spindles and Ia afferents present, but also they were supernumerary in distal muscles such as the soleus, medial gastrocnemius, and extensor hallucis longus. Concomitantly, a deficiency of Golgi tendon organs (GTOs) and Ib afferents was observed in distal muscles, as if supernumerary spindles formed at the expense of tendon organs in the absence of Er81. Thus, ER81 may be involved in mechanisms that regulate acquisition of the Ia and Ib phenotypes by subsets of proprioceptive muscle afferents. Segmental differences in muscle spindle and GTO dependence on ER81 suggest that more than one ETS transcription factor may participate in the regulation of limb proprioceptive system assembly in the mouse.

Development of mechanoreceptor numbers in embryonic chick-quail chimeras.

Our experiments addressed the problem of the regulation of the number of mechanoreceptors by sensory axons and/or their peripheral target tissues. According to a previous study (Zelená et al. 1997) white leghorn chickens have more muscle spindles in the plantaris muscle (45.4+/-7.8; mean+/-SD) than the Japanese quail (35.3+/-4.8) and significantly more Herbst corpuscles in the crural region (380.0+/-85.0) than the quail (124.9+/-32.8). Embryonic chick-quail chimeras were therefore used as a model with distinct recombinations of the nerve supply and peripheral tissue for studying the developmental control of these mechanoreceptors. The chick host leg bud was replaced with a quail leg bud of equal age and vice versa on embryonic day 3, prior to the onset of innervation of the periphery. Shortly before hatching the chimeras were sacrificed and muscle spindles and Herbst corpuscles counted. Recombinations of chicken nerves with quail limb buds have shown that the richer nerve supply by chick Ia axons induced a significant increase in the number of muscle spindles in the plantaris muscles (55.5+/-13.4) of the grafted quail limb. In some instances, a similar increase in spindle numbers was also found in control legs grafted onto hosts of the same species. In the reverse type of chimera where chick embryo legs were grafted onto quail hosts, spindles developed in lower numbers (27.3+/-3.2). In that case the lower number of Ia axons in quail nerves induced a lower number of spindles in the chicken muscle. The numbers of Herbst corpuscles were, however, low in both types of chimera. Quail legs grafted onto host chick embryos contained 126.8+/-26.4 corpuscles, presumably due to a restrictive influence of the smaller crural area in the quail. Chick legs grafted onto quail hosts had only 99.6+/-34.1 crural corpuscles; the target area in chick embryo legs failed to attract more quail axons and/or to induce axonal sprouting. The developmental regulation of the number of the two types of mechanoreceptors examined in our study thus differ. While sensory axons appear to play the dominant role in the development of muscle spindles, their role seems to be restricted by hitherto unknown peripheral factors during the development of Herbst corpuscles.

Reconstruction of elbow flexion by transposition of pedicled long head of triceps brachii muscle.

A new technique of restored flexion in the elbow joint in an inveterate injury of the brachial plexus is described. The insertion of the long head of the triceps brachii muscle was transferred with an intact nervous and vascular supply to the anterior brachial region and sutured above the radial tuberosity with the insertion tendon of the biceps brachii muscle. The muscle strength three months after surgery according to the muscle test was 4-. Flexion in the elbow joint was possible up to 85 degrees. Extension in the elbow joint was preserved, the muscle strength was 3. Anatomical investigation revealed that the mean length of the nerve of the long head of the triceps was 5.5 cm, the number of terminal branches was 3-4, 70% of the vascular supply was from the brachial artery, the length of the vascular bundle was 3.6 cm. In 33% there was an additional neurovascular hilus which was 2-3 cm distally from the main hilus. The investigation confirms that the neurovascular pedicle of the long head of the triceps brachii muscle is sufficiently mobile and damage by traction during transposition of the insertion tendon is therefore not likely. Transfer of the long head of the triceps brachii muscle in inveterate injuries of the brachial plexus is a suitable alternative for reconstruction of nerves or transfer of other muscles to restore flexion in the elbow joint.

Crural Herbst corpuscles in chicken and quail: numbers and structure.

Herbst corpuscles were studied in the crural region of perinatal and adult chicken and quail in order to find out their number and dimensions and to learn more about their structure, especially in relation to size. Crural corpuscles are arrayed in an encapsulated string between tibia and fibula. They are closely packed together; a small number of corpuscles is found apart from the string, often attached to the periost. The strings of corpuscles are approximately 40 mm long in adult chicken and 20 mm long in the quail. The crural region of the chicken contains 382.8 +/- 90.9 (mean +/- SD) corpuscles, the numbers ranging from 301 to 582; in the quail, the mean number is 119.2 +/- 27.9, with a range from 83 to 167 corpuscles. In the chicken, one axon supplies an average of 1.60 corpuscles; in the quail, the relation of axons to corpuscles is approximately 0.92. In both species, final numbers of crural corpuscles are already attained before hatching and no difference is found in the mean number and range of corpuscles between perinatal and adult birds. In both chicken and quail, individual strings contain corpuscles of various sizes, from large to very small. The chicken corpuscles are generally twice as large in diameter and often longer than those of the quail. The corpuscles are composed of an axon terminal that projects two rows of axonal spines into the clefts of the inner core and ends with an ultraterminal bulb; the terminal is surrounded with a bilaterally symmetrical inner core, amorphous inner space containing collagen fibrils of various thickness, and a capsule. Large chicken corpuscles contain inner cores composed of up to 100 lamellae, while quail inner cores have half that number at the most. The capsules are usually composed of 8 to 10 lamellar layers in both species, but they are thicker in the chicken than in the quail. The possible functional significance of individual structural components of Herbst corpuscles is discussed.