Endoscopically assisted nerve decompression of rare nerve compression syndromes at the upper extremity

BACKGROUND Besides carpal tunnel and cubital tunnel syndrome, other nerve compression or constriction syndromes exist at the upper extremity. This study was performed to evaluate and summarize our initial experience with endoscopically assisted decompression. MATERIALS AND METHODS Between January 2011 and March 2012, six patients were endoscopically operated for rare compression or hour-glass-like constriction syndrome. This included eight decompressions: four proximal radial nerve decompressions, and two combined proximal median nerve and anterior interosseus nerve decompressions. Surgical technique and functional outcomes are presented. RESULTS There were no intraoperative complications in the series. Endoscopy allowed both identifying and removing all the compressive structures. In one case, the proximal radial neuropathy developed for 10 years without therapy and a massive hour-glass nerve constriction was observed intraoperatively which led us to perform a concurrent complementary tendon transfer to improve fingers and thumb extension. Excellent results were achieved according to the modified Roles and Maudsley classification in five out of six cases. All but one patient considered the results excellent. The poorest responder developed a CRPS II and refused post-operative physiotherapy. CONCLUSION Endoscopically assisted decompression in rare compression syndrome of the upper extremity is highly appreciated by patients and provides excellent functional results. This minimally invasive surgical technique will likely be further described in future clinical studies.

Papain-induced in vitro disc degeneration model for the study of injectable nucleus pulposus therapy

BACKGROUND CONTEXT Proteolytic enzyme digestion of the intervertebral disc (IVD) offers a method to simulate a condition of disc degeneration for the study of cell-scaffold constructs in the degenerated disc. PURPOSE To characterize an in vitro disc degeneration model (DDM) of different severities of glycosaminoglycans (GAG) and water loss by using papain, and to determine the initial response of the human mesenchymal stem cells (MSCs) introduced into this DDM. STUDY DESIGN Disc degeneration model of a bovine disc explant with an end plate was induced by the injection of papain at various concentrations. Labeled MSCs were later introduced in this model. METHODS Phosphate-buffered saline (PBS control) or papain in various concentrations (3, 15, 30, 60, and 150 U/mL) were injected into the bovine caudal IVD explants. Ten days after the injection, GAG content of the discs was evaluated by dimethylmethylene blue assay and cell viability was determined by live/dead staining together with confocal microscopy. Overall matrix composition was evaluated by histology, and water content was visualized by magnetic resonance imaging. Compressive and torsional stiffness of the DDM were also recorded. In the second part, MSCs were labeled with a fluorescence cell membrane tracker and injected into the nucleus of the DDM or a PBS control. Mesenchymal stem cell viability and distribution were evaluated by confocal microscopy. RESULTS A large drop of GAG and water content of the bovine disc were obtained by injecting >30 U/mL papain. Magnetic resonance imaging showed Grade II, III, and IV disc degeneration by injecting 30, 60, and 150 U/mL papain. A cavity in the center of the disc could facilitate later injection of the nucleus pulposus tissue engineering construct while retaining an intact annulus fibrosus. The remaining disc cell viability was not affected. Mesenchymal stem cells injected into the protease-treated DDM disc showed significantly higher cell viability than when injected into the PBS-injected control disc. CONCLUSIONS By varying the concentration of papain for injection, an increasing amount of GAG and water loss could be induced to simulate the different severities of disc degeneration. MSC suspension introduced into the disc has a very low short-term survival. However, it should be clear that this bovine IVD DDM does not reflect a clinical situation but offers exciting possibilities to test novel tissue engineering protocols.

Characteristics of rod regeneration in a novel zebrafish retinal degeneration model using N-methyl-N-nitrosourea (MNU)

Primary loss of photoreceptors caused by diseases such as retinitis pigmentosa is one of the main causes of blindness worldwide. To study such diseases, rodent models of N-methyl-N-nitrosourea (MNU)-induced retinal degeneration are widely used. As zebrafish (Danio rerio) are a popular model system for visual research that offers persistent retinal neurogenesis throughout the lifetime and retinal regeneration after severe damage, we have established a novel MNU-induced model in this species. Histology with staining for apoptosis (TUNEL), proliferation (PCNA), activated Müller glial cells (GFAP), rods (rhodopsin) and cones (zpr-1) were performed. A characteristic sequence of retinal changes was found. First, apoptosis of rod photoreceptors occurred 3 days after MNU treatment and resulted in a loss of rod cells. Consequently, proliferation started in the inner nuclear layer (INL) with a maximum at day 8, whereas in the outer nuclear layer (ONL) a maximum was observed at day 15. The proliferation in the ONL persisted to the end of the follow-up (3 months), interestingly, without ongoing rod cell death. We demonstrate that rod degeneration is a sufficient trigger for the induction of Müller glial cell activation, even if only a minimal number of rod cells undergo cell death. In conclusion, the use of MNU is a simple and feasible model for rod photoreceptor degeneration in the zebrafish that offers new insights into rod regeneration.

Effect of phrenic nerve palsy on early postoperative lung function after pneumonectomy: a prospective study

BACKGROUND The issue of phrenic nerve preservation during pneumonectomy is still an unanswered question. So far, its direct effect on immediate postoperative pulmonary lung function has never been evaluated in a prospective trial. METHODS We conducted a prospective crossover study including 10 patients undergoing pneumonectomy for lung cancer between July 2011 and July 2012. After written informed consent, all consecutive patients who agreed to take part in the study and in whom preservation of the phrenic nerve during operation was possible, were included in the study. Upon completion of lung resection, a catheter was placed in the proximal paraphrenic tissue on the pericardial surface. After an initial phase of recovery of 5 days all patients underwent ultrasonographic assessment of diaphragmatic motion followed by lung function testing with and without induced phrenic nerve palsy. The controlled, temporary paralysis of the ipsilateral hemidiaphragm was achieved by local administration of lidocaine 1% at a rate of 3 mL/h (30 mg/h) via the above-mentioned catheter. RESULTS Temporary phrenic nerve palsy was accomplished in all but 1 patient with suspected catheter dislocation. Spirometry showed a significant decrease in dynamic lung volumes (forced expiratory volume in 1 second and forced vital capacity; p < 0.05) with the paralyzed hemidiaphragm. Blood oxygen saturation levels did not change significantly. CONCLUSIONS Our results show that phrenic nerve palsy causes a significant impairment of dynamic lung volumes during the early postoperative period after pneumonectomy. Therefore, in these already compromised patients, intraoperative phrenic nerve injury should be avoided whenever possible.

The role of intercostal nerve preservation in pain control after thoracotomy

OBJECTIVES Pain control after thoracotomy is an important issue that affects the outcome in thoracic surgery. Intercostal nerve preservation (ICNP) has increased interest in the outcomes of conventional thoracotomy. The current study critically evaluates the role of preservation of the intercostal nerve in early and late pain control and its benefit in patients undergoing thoracotomy. METHODS Data obtained prospectively between January 2006 and December 2010 by a study colleague at our division of General Thoracic Surgery were retrospectively analysed. There were 491 patients who underwent thoracotomy. Eighty-one patients were excluded from the study due to incompatible data. Patients were divided into two groups according to the intercostal nerve state: Group I consisted of patients with ICNP and Group II consisted of patients with intercostal nerve sacrifice. RESULTS Group I consisted of 288 patients [206 male (71%), P < 0.001, mean age 66 years]. Group II consisted of 122 patients [79 male (64%), P = 0.001, mean age 66 years]. There was less use of opiate in Group I (P = 0.019). Early mobilization of the patients was significantly higher in Group I (P = 0.031). The rate of pneumonia and re-admission to the intensive care unit was higher in Group II (P = 0.017 and 0.023, respectively). The rate of pain-free patients at discharge was significantly higher in Group I (P = 0.028). A 2-week follow-up after hospital discharge showed parasternal hypoesthesia to be more in Group II (P = 0.034). Significant patient contentment in Group I was noticed (P = 0.014). Chronic post-thoracotomy pain (CPTP) was higher in Group II (P = 0.016). CONCLUSIONS ICNP without harvesting an intercostal muscle flap achieves excellent outcomes in controlling acute post-thoracotomy pain and CPTP. ICNP is an effective, simple method to perform, and it should be considered as standard in performing thoracotomy.

A papain-induced disc degeneration model for the assessment of thermo-reversible hydrogel-cells therapeutic approach

Nucleus pulposus (NP) regeneration by the application of injectable cell-embedded hydrogels is an appealing approach for tissue engineering. We investigated a thermo-reversible hydrogel (TR-HG), based on a modified polysaccharide with a thermo-reversible polyamide [poly(N-isopropylacrylamide), pNIPAM], which is made to behave as a liquid at room temperature and hardens at > 32 °C. In order to test the hydrogel, a papain-induced bovine caudal disc degeneration model (PDDM), creating a cavity in the NP, was employed. Human mesenchymal stem cells (hMSCs) or autologous bovine NP cells (bNPCs) were seeded in TR-HG; hMSCs were additionally preconditioned with rhGDF-5 for 7 days. Then, TR-HG was reversed to a fluid and the cell suspension injected into the PDDM and kept under static loading for 7 days. Experimental design was: (D1) fresh disc control + PBS injection; (D2) PDDM + PBS injection; (D3) PDDM + TR-HG (material control); (D4) PDDM + TR-HG + bNPCs; (D5) PDDM + TR-HG + hMSCs. Magnetic resonance imaging performed before and after loading, on days 9 and 16, allowed imaging of the hydrogel-filled PDDM and assessment of disc height and volume changes. In gel-injected discs the NP region showed a major drop in volume and disc height during culture under static load. The RT–PCR results of injected hMSCs showed significant upregulation of ACAN, COL2A1, VCAN and SOX9 during culture in the disc cavity, whereas the gene expression profile of NP cells remained unchanged. The cell viability of injected cells (NPCs or hMSCs) was maintained at over 86% in 3D culture and dropped to ~72% after organ culture. Our results underline the need for load-bearing hydrogels that are also cyto-compatible.

Feasibility of Using EMG for Early Detection of the Facial Nerve During Robotic Direct Cochlear Access

HYPOTHESIS Facial nerve monitoring can be used synchronous with a high-precision robotic tool as a functional warning to prevent of a collision of the drill bit with the facial nerve during direct cochlear access (DCA). BACKGROUND Minimally invasive direct cochlear access (DCA) aims to eliminate the need for a mastoidectomy by drilling a small tunnel through the facial recess to the cochlea with the aid of stereotactic tool guidance. Because the procedure is performed in a blind manner, structures such as the facial nerve are at risk. Neuromonitoring is a commonly used tool to help surgeons identify the facial nerve (FN) during routine surgical procedures in the mastoid. Recently, neuromonitoring technology was integrated into a commercially available drill system enabling real-time monitoring of the FN. The objective of this study was to determine if this drilling system could be used to warn of an impending collision with the FN during robot-assisted DCA. MATERIALS AND METHODS The sheep was chosen as a suitable model for this study because of its similarity to the human ear anatomy. The same surgical workflow applicable to human patients was performed in the animal model. Bone screws, serving as reference fiducials, were placed in the skull near the ear canal. The sheep head was imaged using a computed tomographic scanner and segmentation of FN, mastoid, and other relevant structures as well as planning of drilling trajectories was carried out using a dedicated software tool. During the actual procedure, a surgical drill system was connected to a nerve monitor and guided by a custom built robot system. As the planned trajectories were drilled, stimulation and EMG response signals were recorded. A postoperative analysis was achieved after each surgery to determine the actual drilled positions. RESULTS Using the calibrated pose synchronized with the EMG signals, the precise relationship between distance to FN and EMG with 3 different stimulation intensities could be determined for 11 different tunnels drilled in 3 different subjects. CONCLUSION From the results, it was determined that the current implementation of the neuromonitoring system lacks sensitivity and repeatability necessary to be used as a warning device in robotic DCA. We hypothesize that this is primarily because of the stimulation pattern achieved using a noninsulated drill as a stimulating probe. Further work is necessary to determine whether specific changes to the design can improve the sensitivity and specificity.

Refractory chronic pelvic pain syndrome in men: can transcutaneous electrical nerve stimulation help?

Objective To evaluate the effect of transcutaneous electrical nerve stimulation (TENS) for treating men with refractory chronic pelvic pain syndrome (CPPS). Patients and Methods A consecutive series of 60 men treated with TENS for refractory CPPS was evaluated prospectively at an academic tertiary referral centre. The effects of treatment were evaluated by a pain diary and by the quality of life item of the National Institutes of Health Chronic Prostatitis Symptom Index at baseline, after 12 weeks of TENS treatment, and at last known follow-up. Adverse events related to TENS were also assessed. Results The mean (95% confidence interval, CI; range) age of the 60 men was 46.9 (43.5–50.3; 21–82) years. TENS was successful after 12 weeks of treatment in 29 (48%) patients and a positive effect was sustained during a mean (95%, CI; range) follow-up of 43.6 (33.2–56; 6–88) months in 21 patients. After 12 weeks of TENS treatment, mean (95% CI) pain visual analogue scale decreased significantly (P < 0.001) from 6.6 (6.3–6.9) to 3.9 (3.2–4.6). Patients' quality of life changed significantly after TENS treatment (P < 0.001). Before TENS, all 60 patients felt mostly dissatisfied (n = 17; 28%), unhappy (n = 28; 47%) or terrible (n = 15; 25%). After 12 weeks of TENS treatment, 29 (48%) patients felt mostly satisfied (n = 5), pleased (n = 18) or delighted (n = 6). No adverse events related to TENS were noted. Conclusion TENS may be an effective and safe treatment for refractory CPPS in men, warranting randomized, placebo-controlled trials.

Transcutaneous electrical nerve stimulation: an effective treatment for refractory non-neurogenic overactive bladder syndrome?

PURPOSE: To assess the effect of transcutaneous electrical nerve stimulation (TENS) for treating refractory overactive bladder syndrome (OAB). PATIENTS AND METHODS: A consecutive series of 42 patients treated with TENS for refractory OAB was prospectively investigated at an academic tertiary referral centre. Effects were evaluated using bladder diary for at least 48 h and satisfaction assessment at baseline, after 12 weeks of TENS treatment, and at the last known follow-up. Adverse events related to TENS were also assessed. RESULTS: Mean age of the 42 patients (25 women, 17 men) was 48 years (range, 18-76). TENS was successful following 12 weeks of treatment in 21 (50 %) patients, and the positive effect was sustained during a mean follow-up of 21 months (range, 6-83 months) in 18 patients. Following 12 weeks of TENS treatment, mean number of voids per 24 h decreased significantly from 15 to 11 (p < 0.001) and mean voided volume increased significantly from 160 to 230 mL (p < 0.001). In addition, TENS completely restored continence in 7 (39 %) of the 18 incontinent patients. Before TENS, all 42 patients were dissatisfied or very dissatisfied; following 12 weeks of TENS treatment, 21 (50 %) patients felt satisfied or very satisfied (p < 0.001). No adverse events related to TENS were noted. CONCLUSIONS: TENS seems to be an effective and safe treatment for refractory OAB warranting randomized, placebo-controlled trials.

Immunohistochemical evaluation of heat shock protein expression in normal canine nerve and peripheral nerve sheath tumours

Abnormal expression of heat shock proteins (HSPs) has been observed in many human neoplasms and such expression has prognostic, predictive and therapeutic implications. The aim of this study was to evaluate immunohistochemically the expression of HSP 27, HSP 32 and HSP 90 in normal canine peripheral nerves and in four benign and 15 malignant canine peripheral nerve sheath tumours (PNSTs). In normal nerve, all of the HSPs were detected in axons, epineurial fibroblasts and scattered Schwann cell bodies. Cytoplasmic expression of HSP 27 was more widespread and intense in benign PNSTs compared with malignant PNSTs (P <0.05). Widespread and intense nuclear expression of HSP 32 was also associated with benign tumours (P <0.01), while high HSP 90 immunoreactivity was detected in all tumours, suggesting that HSP 90 might represent a new therapeutic target.

Microcystic macular edema: retrograde maculopathy caused by optic neuropathy

PURPOSE To investigate retrograde axonal degeneration for its potential to cause microcystic macular edema (MME), a maculopathy that has been previously described in patients with demyelinating disease. To identify risk factors for MME and to expand the anatomic knowledge on MME. DESIGN Retrospective case series. PARTICIPANTS We included 117 consecutive patients and 180 eyes with confirmed optic neuropathy of variable etiology. Patients with glaucoma were excluded. METHODS We determined age, sex, visual acuity, etiology of optic neuropathy, and the temporal and spatial characteristics of MME. Eyes with MME were compared with eyes with optic neuropathy alone and to healthy fellow eyes. With retinal layer segmentation we quantitatively measured the intraretinal anatomy. MAIN OUTCOME MEASURES Demographic data, distribution of MME in the retina, and thickness of retinal layers were analyzed. RESULTS We found MME in 16 eyes (8.8%) from 9 patients, none of whom had multiple sclerosis or neuromyelitis optica. The MME was restricted to the inner nuclear layer (INL) and had a characteristic perifoveal circular distribution. Compared with healthy controls, MME was associated with significant thinning of the ganglion cell layer and nerve fiber layer, as well as a thickening of the INL and the deeper retinal layers. Youth is a significant risk factor for MME. CONCLUSIONS Microcystic macular edema is not specific for demyelinating disease. It is a sign of optic neuropathy irrespective of its etiology. The distinctive intraretinal anatomy suggests that MME is caused by retrograde degeneration of the inner retinal layers, resulting in impaired fluid resorption in the macula.

Development of an ultrasound-guided technique for pudendal nerve block in cat cadavers.

The objective of this prospective experimental cadaveric study was to develop an ultrasound-guided technique to perform an anaesthetic pudendal nerve block in male cats. Fifteen fresh cadavers were used for this trial. A detailed anatomical dissection was performed on one cat in order to scrutinise the pudendal nerve and its ramifications. In a second step, the cadavers of six cats were used to test three different ultrasonographic approaches to the pudendal nerve: the deep dorso-lateral, the superficial dorso-lateral and the median transperineal. Although none of the approaches allowed direct ultrasonographical identification of the pudendal nerve branches, the deep dorso-lateral was found to be the most advantageous one in terms of practicability and ability to identify useful and reliable landmarks. Based on these findings, the deep dorso-lateral approach was selected as technique of choice for tracer injections (0.1 ml 1% methylene blue injected bilaterally) in six cat cadavers distinct from those used for the ultrasonographical study. Anatomical dissection revealed a homogeneous spread of the tracer around the pudendal nerve sensory branches in all six cadavers. Finally, computed tomography was performed in two additional cadavers after injection of 0.3 ml/kg (0.15 ml/kg per each injection sites, left and right) contrast medium through the deep dorso-lateral approach in order to obtain a model of volume distribution applicable to local anaesthetics. Our findings in cat cadavers indicate that ultrasound-guided pudendal nerve block is feasible and could be proposed to provide peri-operative analgesia in clinical patients undergoing perineal urethrostomy.

Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.

BACKGROUND: Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age-related macular degeneration (AMD), the most common cause of visual impairment in industrialized countries. METHODS/PRINCIPAL FINDINGS: We investigated the association between the LOC387715 A69S and complement component C3 R102G risk alleles in the Finnish case-control material and found a significant association with both variants (OR 2.98, p = 3.75 x 10(-9); non-AMD controls and OR 2.79, p = 2.78 x 10(-19), blood donor controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood donor controls), respectively. Previously, we have shown a strong association between complement factor H (CFH) Y402H and AMD in the Finnish population. A carrier of at least one risk allele in each of the three susceptibility loci (LOC387715, C3, CFH) had an 18-fold risk of AMD when compared to a non-carrier homozygote in all three loci. A tentative gene-gene interaction between the two major AMD-associated loci, LOC387715 and CFH, was found in this study using a multiplicative (logistic regression) model, a synergy index (departure-from-additivity model) and the mutual information method (MI), suggesting that a common causative pathway may exist for these genes. Smoking (ever vs. never) exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 genotype. Population attributable risks (PAR) for the CFH, LOC387715 and C3 variants were 58.2%, 51.4% and 5.8%, respectively, the summary PAR for the three variants being 65.4%. CONCLUSIONS/SIGNIFICANCE: Evidence for gene-gene interaction between two major AMD associated loci CFH and LOC387715 was obtained using three methods, logistic regression, a synergy index and the mutual information (MI) index.

Eomesodermin, a target gene of Pou4f2, is required for retinal ganglion cell and optic nerve development in the mouse.

The mechanisms regulating retinal ganglion cell (RGC) development are crucial for retinogenesis and for the establishment of normal vision. However, these mechanisms are only vaguely understood. RGCs are the first neuronal lineage to segregate from pluripotent progenitors in the developing retina. As output neurons, RGCs display developmental features very distinct from those of the other retinal cell types. To better understand RGC development, we have previously constructed a gene regulatory network featuring a hierarchical cascade of transcription factors that ultimately controls the expression of downstream effector genes. This has revealed the existence of a Pou domain transcription factor, Pou4f2, that occupies a key node in the RGC gene regulatory network and that is essential for RGC differentiation. However, little is known about the genes that connect upstream regulatory genes, such as Pou4f2 with downstream effector genes responsible for RGC differentiation. The purpose of this study was to characterize the retinal function of eomesodermin (Eomes), a T-box transcription factor with previously unsuspected roles in retinogenesis. We show that Eomes is expressed in developing RGCs and is a mediator of Pou4f2 function. Pou4f2 directly regulates Eomes expression through a cis-regulatory element within a conserved retinal enhancer. Deleting Eomes in the developing retina causes defects reminiscent of those in Pou4f2(-/-) retinas. Moreover, myelin ensheathment in the optic nerves of Eomes(-/-) embryos is severely impaired, suggesting that Eomes regulates this process. We conclude that Eomes is a crucial regulator positioned immediately downstream of Pou4f2 and is required for RGC differentiation and optic nerve development.