Is ventriculomegaly and hindbrain herniation seen before and after prenatal neural tube defect repair associated with a worse functional level than anatomical level at birth?

OBJECTIVE: To determine if the evaluation of the fetal ventricular system and hindbrain herniation (HBH) is associated with motor outcome at birth in prenatally repaired open neural tube defect (NTD). METHODS: Retrospective cohort study of 47 patients with NTD who underwent prenatal repair (17 fetoscopic; 30 open-hysterotomy). At referral and 6 weeks postoperatively, the degree of HBH, ventricular atrial widths and ventricular volume were evaluated by MRI. Head circumference and ventricular atrial widths were measured on ultrasound at referral and during the last ultrasound before delivery. Anatomic level of the lesion (LL) was determined based on the upper bony spinal defect detected by ultrasound. We considered the functional level as worse than anatomical level at birth when the motor level was equal or worse than the anatomical LL. RESULTS: 26% (12/47) of the cases showed worse functional level than anatomical level at birth. Having a HBH below C1 at the time of referral was associated with a worse functional level than anatomical level at birth (OR = 9.7, CI95 [2.2-42.8], p < 0.01). None of the other brain parameters showed a significant association with motor outcomes at birth. CONCLUSIONS: HBH below C1 before surgery was associated with a worse functional level than anatomical level at birth.

Cryptic responses to tissue manipulations in avian embryos.

Experimental embryology performed on avian embryos combines tissue manipulations and cell-labeling methods with increasing opportunities and demands for critical assays of the results. These approaches continue to reveal unexpected complexities in the normal patterns of cell movement and tissue origins, documentation of which is critical to unraveling the intricacies of cell and tissue interactions during embryogenesis. Viktor Hamburger's many pioneering contributions helped launch and promote the philosophical as well as technical elements of avian experimental embryology. Furthermore, his scholarship and profoundly positive presence influenced not just those of us fortunate to have trained with him, but several generations of developmental biologists. The first part of this article presents examples of the opportunities and rewards that have occurred due to his influences. Surgical manipulation of avian embryonic tissues always introduces a greater number of variables than the experimenter can control for or, often, readily identify. We present the results of dorsal and ventral lesions of hindbrain segments, which include defects in structures within, beside, and also at a considerable distance from the site of lesion. Extramedullary loops of longitudinal tract axons exit and re-enter the neural tube, and intra-medullary proliferation of blood vessels is expanded. Peripherally, the coalescence of neural crest- and placode-derived neuroblasts is disrupted. As expected, motor neurons and their projections close to the sites of lesion are compromised. However, an unexpected finding is that the normal projections of cranial nerves located distant to the lesion site were also disrupted. Following brainstem lesions in the region of rhombomeres 3, 4 or 5, trigeminal or oculomotor axons penetrated the lateral rectus muscle. Surprisingly, the ability of VIth nerve axons to reach the lateral rectus muscle was not destroyed in most cases, even though the terrain through which they needed to pass was disrupted. These axons typically followed a more ventral course than normal, and usually, the axons emerging from individual roots failed to fasciculate into a common VIth nerve, which suggests that each rootlet contains pathfinder-competent axons. The lesson from these lesions is that surgical intervention in avian embryos may have substantial effects upon tissues within, adjacent to, and distant to those that are being manipulated.

The effect of embryonic cerebrospinal fluid pressure and morphogenetic brain expansion on wound healing in the midbrain of the chick embryo.

The role of increased cerebrospinal fluid pressure and morphogenetic brain expansion on midbrain wound healing was studied in chick embryos at stages 16-22. The embryos were divided into six groups as follows: group I (stages 16/17), group II (stages 18/19), group III (stages 20-22), group IV (stages 18/19), group V (stages 20-22) and group VI (stages 18/19). The mid-brains of embryos of groups I-III were wounded and the embryos re-incubated for varying periods up to 24 h. The neuroepithelial wounds of all group-I embryos healed completely within 24 h. However, complete healing was observed in only 25% of wounds in group II and 11.4% in group III by 24 h. To reduce cerebrospinal fluid pressure and thus slow down brain expansion, longitudinal wounds (about 0.8 mm long) were made in the hindbrain roof plate of group-IV and group-V embryos, and puncture wounds (0.1 mm in diameter) also in the hindbrain roof plate of group-VI embryos. This allowed cerebrospinal fluid to escape prior to wounding the midbrain. There was a significant increase in the proportion of group-IV and group-V embryos with completely healed midbrain neuroepithelial wounds (77.3% and 28.6% respectively). However, a comparison between groups II and VI embryos yielded no statistically significant difference in healing. Thus, increasing cerebrospinal fluid pressure and brain expansion adversely affect midbrain neuroepithelial wound healing.

Pontomedullary tears and other gross brainstem injuries after vehicular accidents.

In a series of 988 autopsied victims of road crashes, there were 36 (3.6%) cases of gross primary brainstem injury. These fell into three groups. The first comprised eight cases of pontomedullary tearing without other gross brain injury: in seven of these, there were associated atlanto-occipital dislocations and/or high cervical fracture-dislocations. The usual cause appeared to be facial impact inducing acute hyperextension. Second, there were 17 cases of pontomedullary tearing associated with other brainstem lacerations and/or major damage elsewhere in the brain: in all, there were fractures of the skull base, typically transverse middle fossa fractures. Most of these injuries appeared to be due to facial impacts transmitting force to the anterior skull base, although hyperextension was also a factor in some. There was a third heterogeneous group of 11 cases with brainstem lacerations in sites other than the pontomedullary junction: in some of these it appeared that the impacts had caused skull base fractures by inducing calvarial torsion. In this series, the proportion of motorcyclists (41.7%) was double the expected figure. The use of a helmet modifies the mechanisms of impact head injury; the overall benefits of helmet use are well established, but there is need for more research on helmet design.

Dendritic amputation redistributes sprouting evoked by axotomy in lamprey central neurons.

In the previous paper (Hall and Cohen, 1988), we showed that axotomy of anterior bulbar cells (ABCs) in the hindbrain of the larval lamprey results in the sprouting of axonlike neurites from either the end of the proximal axon stump, the dendritic tips, or both, depending on the site of axotomy. Here we show that, unlike axotomy, dendritic amputation (dendrotomy) does not by itself induce sprouting from ABCs. However, dendrotomy does induce sprouting from dendrites in the immediate vicinity of the dendritic lesion in cells that have been previously axotomized. We found that dendrotomy acts primarily to rearrange the distribution of sprouts induced by axotomy rather than serving as an additional stimulus to neurite outgrowth. We propose that (1) dendritic sprouting in ABCs occurs because the dendritic tips become attractive sites for sprout initiation when they are either directly injured (as with dendrotomy) or are situated relatively close to the site of injury (as with axotomy close to the soma), and (2) the axon stump, dendritic stumps, and uninjured dendritic tips of the cell compete to initiate a limited total amount of sprouting induced by axotomy. The probability that a given locus will support sprouting is determined both by its proximity to the nearest lesion site and by whether there are other attractive potential sprouting sites in the cell.

The pattern of dendritic sprouting and retraction induced by axotomy of lamprey central neurons.

We have investigated some of the factors controlling the distribution of axonal and dendritic sprouting following axotomy of a subset of Muller giant interneurons (anterior bulbar cells or ABCs) in the hindbrain of the larval sea lamprey (Petromyzon marinus). Sprouts originated from different sites in the cell depending on the distance of the axonal lesion from the soma. When the axon was cut close to the soma (within 500 microns), the dendritic tips sprouted profusely, whereas the proximal axon stump showed few sprouts and frequently disappeared entirely. Axotomy further from the soma (1000-1400 microns) resulted in less sprouting from the dendrites and more from the axon stump, with the total amount of dendritic plus axonal sprouting remaining constant. Axotomy at sites distant from the soma (1 cm or more) did not result in dendritic sprouting. No sprouts were ever observed emerging from the soma proper or from the axon stump except at the lesion site. Neuritic sprouts from dendrites and axon were similar in their gross morphology. Sprouts resembled axons rather than dendrites whatever their sites of origin; they followed linear, rostrocaudally oriented paths in the "basal plate" region of the hindbrain. Dendritic and axonal sprouts grew both rostrally and caudally within the brain. Either "close" or "distant" axotomy resulted in the retraction of the dendritic tree and of both dendritic and axonal sprouts by several months postaxotomy. Reaxotomy close to the soma 30 d after a distant axotomy accelerated the onset of this evoked dendritic retraction. Reaxotomy close to the soma also induced sprouting significantly sooner than did close axotomy alone. These results suggest that axotomy close to the soma causes axonal regeneration to be shunted into ectopic locations at the dendritic tips. The emerging sprouts then follow guidance cues appropriate for regenerating ABC axons.