Clinical aspects of ballistic peripheral nerve injury: shrapnel versus gunshot

Objectives

Ballistic injuries to peripheral nerves pose special challenges in terms of indications, timing and type of surgical intervention. The aim of the present work was to analyze our experience in the surgical treatment of peripheral nerve ballistic injuries with respect to the mechanism of injury (gunshot versus shrapnel), and identify common and dissimilar prognostic factors in both types of injury.

Methods

This study was conducted on 42 patients totaling 58 nerves. Twenty-two patients (32 nerves) were injured by gunshot and 20 patients (26 nerves) by shrapnel. Median postoperative follow-up was 33 months (range 12 months to 14 years).

Results

Overall postoperative outcome appears to be more favorable for gunshot-wound (GSW) patients than shrapnel-injured patients, especially in terms of neuropathic pain relief (75 % vs. 58 % respectively, p < 0.05). Presence of foreign particles in shrapnel injured patients has a negative impact on the surgical outcome in terms of rate of pain improvement (28 % compared to 67 % in patients with and without foreign particles, respectively). Nerve graft reconstruction, rather than neurolysis, seems to be the more beneficial treatment for shrapnel-induced neuropathic pain (100 % vs. 47 % in improvement rate, respectively). Early surgical intervention (median 2 months after injury) significantly relieved neuropathic pain in 83 % of shrapnel-injured patients compared to 58 % in patients operated later.

Conclusions

This study suggests that shrapnel injury is more destructive for nerve tissue than gunshot injury. Our impression is that early surgical intervention in shrapnel injuries and split nerve grafting (especially when small fragments are recognized in the nerve) significantly improve the patient’s functional activity and quality of life.     

Aldosterone-sensitive neurons in the nucleus of the solitary: efferent projections

The nucleus of the solitary tract (NTS) contains a subpopulation of neurons that express the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2), which makes them uniquely sensitive to aldosterone. These neurons may drive sodium appetite, which is enhanced by aldosterone. Anterograde and retrograde neural tracing techniques were used to reveal the efferent projections of the HSD2 neurons in the rat. First, the anterograde tracer Phaseolus vulgaris leucoagglutinin was used to label axonal projections from the medial NTS. Then, NTS-innervated brain regions were injected with a retrograde tracer, cholera toxin beta subunit, to determine which sites are innervated by the HSD2 neurons. The HSD2 neurons project mainly to the ventrolateral bed nucleus of the stria terminalis (BSTvl), the pre-locus coeruleus (pre-LC), and the inner division of the external lateral parabrachial nucleus (PBel). They also send minor axonal projections to the midbrain ventral tegmental area, lateral and paraventricular hypothalamic nuclei, central nucleus of the amygdala, and periaqueductal gray matter. The HSD2 neurons do not innervate the ventrolateral medulla, a key brainstem autonomic site. Additionally, our tracing experiments confirmed that the BSTvl receives direct axonal projections from the neighboring A2 noradrenergic neurons in the NTS, and from the same pontine sites that receive major inputs from the HSD2 neurons (PBel and pre-LC). The efferent projections of the HSD2 neurons may provide new insights into the brain circuitry responsible for sodium appetite.     

Aldosterone-sensitive neurons in the nucleus of the solitary tract: bidirectional connections with the central nucleus of the amygdala

The HSD2 (11-beta-hydroxysteroid dehydrogenase type 2-expressing) neurons in the nucleus of the solitary tract (NTS) of the rat are aldosterone-sensitive and have been implicated in sodium appetite. The central nucleus of the amygdala (CeA) has been shown to modulate salt intake in response to aldosterone, so we investigated the connections between these two sites. A prior retrograde tracing study revealed only a minor projection from the HSD2 neurons directly to the CeA, but these experiments suggested that a more substantial projection may be relayed through the parabrachial nucleus. Small injections of cholera toxin beta subunit (CTb) into the external lateral parabrachial subnucleus (PBel) produced both retrograde cell body labeling in the HSD2 neurons and anterograde axonal labeling in the lateral subdivision of the CeA. Also, injections of either CTb or Phaseolus vulgaris leucoagglutinin into the medial subdivision of the CeA labeled a descending projection from the amygdala to the medial NTS. Axons from the medial CeA formed numerous varicosities and terminals enveloping the HSD2 neurons. Complementary CTb injections, centered in the HSD2 subregion of the NTS, retrogradely labeled neurons in the medial CeA. These bidirectional projections could form a functional circuit between the HSD2 neurons and the CeA. The HSD2 neurons may represent one of the functional inputs to the lateral CeA, and their activity may be modulated by a return projection from the medial CeA. This circuit could provide a neuroanatomical basis for the modulation of salt intake by the CeA.     

Sodium deprivation and salt intake activate separate neuronal subpopulations in the nucleus of the solitary tract and the parabrachial complex

Salt intake is an established response to sodium deficiency, but the brain circuits that regulate this behavior remain poorly understood. We studied the activation of neurons in the nucleus of the solitary tract (NTS) and their efferent target nuclei in the pontine parabrachial complex (PB) in rats during sodium deprivation and after salt intake. After 8-day dietary sodium deprivation, immunoreactivity for c-Fos (a neuronal activity marker) increased markedly within the aldosterone-sensitive neurons of the NTS, which express the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2). In the PB, c-Fos labeling increased specifically within two sites that relay signals from the HSD2 neurons to the forebrain--the pre-locus coeruleus and the innermost region of the external lateral parabrachial nucleus. Then, 1-2 hours after sodium-deprived rats ingested salt (a hypertonic 3% solution of NaCl), c-Fos immunoreactivity within the HSD2 neurons was virtually eliminated, despite a large increase in c-Fos activation in the surrounding NTS (including the A2 noradrenergic neurons) and area postrema. Also after salt intake, c-Fos activation increased within pontine nuclei that relay gustatory (caudal medial PB) and viscerosensory (rostral lateral PB) information from the NTS to the forebrain. Thus, sodium deficiency and salt intake stimulate separate subpopulations of neurons in the NTS, which then transmit this information to the forebrain via largely separate relay nuclei in the PB complex. These findings offer new perspectives on the roles of sensory information from the brainstem in the regulation of sodium appetite.     

Delimiting subterritories of the human subthalamic nucleus by means of microelectrode recordings and a Hidden Markov Model

Positive therapeutic response without adverse side effects to subthalamic nucleus deep brain stimulation (STN DBS) for Parkinson's disease (PD) depends to a large extent on electrode location within the STN. The sensorimotor region of the STN (seemingly the preferred location for STN DBS) lies dorsolaterally, in a region also marked by distinct beta (13–30 Hz) oscillations in the parkinsonian state. In this study, we present a real‐time method to accurately demarcate subterritories of the STN during surgery, based on microelectrode recordings (MERs) and a Hidden Markov Model (HMM). Fifty‐six MER trajectories were used, obtained from 21 PD patients who underwent bilateral STN DBS implantation surgery. Root mean square (RMS) and power spectral density (PSD) of the MERs were used to train and test an HMM in identifying the dorsolateral oscillatory region (DLOR) and nonoscillatory subterritories within the STN. The HMM demarcations were compared to the decisions of a human expert. The HMM identified STN‐entry, the ventral boundary of the DLOR, and STN‐exit with an error of ?0.09 ± 0.35, ?0.27 ± 0.58, and ?0.20 ± 0.33 mm, respectively (mean ± standard deviation), and with detection reliability (error < 1 mm) of 95, 86, and 91%, respectively. The HMM was successful despite a very coarse clustering method and was robust to parameter variation. Thus, using an HMM in conjunction with RMS and PSD measures of intraoperative MER can provide improved refinement of STN entry and exit in comparison with previously reported automatic methods, and introduces a novel (intra‐STN) detection of a distinct DLOR‐ventral boundary. © 2009 Movement Disorder Society     

Healing Kinetics of Periapical Lesions Enhanced by the Apexum Procedure: A Clinical Trial

The new Apexum procedure (Apexum Ltd, Or-Yehuda, Israel) is based on a minimally invasive removal of periapical chronically inflamed tissues through a root canal access. Its goal is to enhance healing kinetics of periapical lesions. This clinical study was conducted to explore the safety and efficacy of this procedure. The Apexum procedure was applied, as a supplementary step, during conventional root canal treatment in 48 teeth with periapical lesions. Safety and efficacy were clinically and radiographically assessed and teeth of the Apexum-treated group were compared with 39 similar teeth treated by the same endodontic procedure with no additional intervention. No adverse events occurred in either the Apexum-treated or conventional treatment groups. Furthermore, healing kinetics was significantly enhanced in the Apexum-treated group (p < 0.005). At 3 and 6 months, 87% and 95% of the lesions in the Apexum-treated group, respectively, presented advanced or complete healing, whereas only 22% and 39% of the lesions in the conventional treatment group presented this degree of healing at 3 and 6 months, respectively.     

Three‐Dimensional Ultrasonography of the Fetal Vermis at 18 to 26 Weeks' Gestation

Objective. The purpose of this study was to establish the normality of the fetal vermis, ie, the time of appearance of the primary fissure, as well as its measurements between 18 and 26 weeks' gestation, using 3‐dimensional (3D) ultrasonography. Methods. A prospective cross‐sectional study of normal singleton pregnancies was conducted. Examinations were performed with high‐resolution transabdominal ultrasonography using the axial plane in 173 fetuses between 18 and 26 weeks' gestation. Postprocessing measurements of the fetal vermis were done with 4‐dimensional software using static volume contrast imaging and tomographic ultrasound imaging in the C‐plane. Detection of the primary fissure was evaluated in all cases, and the time of appearance was documented. Results. Adequate vermis measurements were obtained in 173 fetuses. Vermian length as a function of gestational age was expressed by regression equations, and the correlation coefficients were found to be highly statistically significant (P < .001). The normal mean ± 2 SD for each gestational week was defined. The primary fissure was observed at 24 weeks' gestation in all cases, at 22 weeks in 94% of cases, and as early as 18 weeks in 40%. Conclusions. This 3D study documents the appearance of the primary fissure and presents the normal range of vermian measurements, confirming normal development of the fetal vermis starting as early as 18 weeks' gestation. It also shows an easy method for visualizing the vermis with 3D ultrasonography at every gestational week regardless of fetal presentation.     

Fractionated radiation facilitates repair and functional motor recovery after spinal cord transection in rat

Previous studies suggest that motor recovery does not occur after spinal cord injury because reactive glia abort the natural repair processes. A permanent wound gap is left in the cord and the brain-cord circuitry consequently remains broken. Single-dose x-irradiation destroys reactive glia at the damage site in transected adult rat spinal cord. The wound then heals naturally, and a partially functional brain-cord circuitry is reconstructed. Timing is crucial; cell ablation is beneficial only within the third week after injury. Data presented here point to the possibility of translating these observations into a clinical therapy for preventing the paralysis following spinal cord injury in the human. The lesion site (at low thoracic level) in severed adult rat spinal cord was treated daily, over the third week postinjury, with protocols of fractionated radiation similar to those for treating human spinal cord tumors. This resulted, as with the single-dose protocol, in wound healing and restoration of some hindquarter motor function; in addition, the beneficial outcome was augmented. Of the restored hindlimb motor functions, weight-support and posture in stance was the only obvious one. Recovery of this motor function was partial to substantial and its incidence was 100% instead of about 50% obtained with the single-dose treatment. None of the hindlimbs, however, regained frequent stepping or any weight-bearing locomotion. These data indicate that the therapeutic outcome may be further augmented by tuning the radiation parameters within the critical time-window after injury. These data also indicate that dose-fractionation is an effective strategy and better than the single-dose treatment for targeting of reactive cells that abort the natural repair, suggesting that radiation therapy could be developed into a therapeutic procedure for repairing injured spinal cord.