Attenuation of a DNA cruciform by a conserved regulator directs T3SS1 mediated virulence in Vibrio parahaemolyticus.

Pathogenic Vibrio species account for 3-5 million annual life-threatening human infections. Virulence is driven by bacterial hemolysin and toxin gene expression often positively regulated by the winged helix-turn-helix (wHTH) HlyU transcriptional regulator family and silenced by histone-like nucleoid structural protein (H-NS). In the case of Vibrio parahaemolyticus, HlyU is required for virulence gene expression associated with type 3 Secretion System-1 (T3SS1) although its mechanism of action is not understood. Here, we provide evidence for DNA cruciform attenuation mediated by HlyU binding to support concomitant virulence gene expression. Genetic and biochemical experiments revealed that upon HlyU mediated DNA cruciform attenuation, an intergenic cryptic promoter became accessible allowing for exsA mRNA expression and initiation of an ExsA autoactivation feedback loop at a separate ExsA-dependent promoter. Using a heterologous E. coli expression system, we reconstituted the dual promoter elements which revealed that HlyU binding and DNA cruciform attenuation were strictly required to initiate the ExsA autoactivation loop. The data indicate that HlyU acts to attenuate a transcriptional repressive DNA cruciform to support T3SS1 virulence gene expression and reveals a non-canonical extricating gene regulation mechanism in pathogenic Vibrio species.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months postdecentralization, eight underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 mo recovery (ObNT-ScNT Reinn). The remaining four were euthanized 18 mo postdecentralization (Decentralized). Results were compared with 18 Controls. Squat-and-void postures were tracked during awake cystometry. None showed squat-and-void postures during the decentralization phase. Seven of eight ObNT-ScNT Reinn began showing such postures by 6 mo postreinnervation; one showed a return of defecation postures. Retrograde dyes were injected into the bladder and urethra 3 wk before euthanasia, at which point, roots and transferred nerves were electrically stimulated to evaluate motor function. Upon L2-L6 root stimulation, five of eight ObNT-ScNT Reinn showed elevated detrusor pressure and four showed elevated urethral pressure, compared with L7-S3 root stimulation. After stimulation of sciatic-to-pudendal transferred nerves, three of eight ObNT-ScNT Reinn showed elevated urethral pressure; all showed elevated anal sphincter pressure. Retrogradely labeled neurons were observed in L2-L6 ventral horns (in laminae VI, VIII, and IX) of ObNT-ScNT Reinn versus Controls in which labeled neurons were observed in L7-S3 ventral horns (in lamina VII). This data supports the use of nerve transfer techniques for the restoration of bladder function.NEW & NOTEWORTHY This data supports the use of nerve transfer techniques for the restoration of bladder function.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral, and anal sphincter function in a dog model. Part 3. nicotinic receptor characterization.

Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: control (9 female and 11 male normal controls, 5 sham operated), Decentralized (9 females, decentralized 6-21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9-13 mo, then reinnervated with 8-12 mo recovery). Muscle strips were collected, mucosa-denuded, and mounted in muscle baths before incubation with neurotransmitter antagonists, and contractions to the nicotinic receptor agonist epibatidine were determined. Strip response to epibatidine, expressed as percent potassium chloride, was similar (∼35% in controls, 30% in Decentralized, and 24% in ObNT-Reinn). Differentially, epibatidine responses in Decentralized and ObNT-Reinn bladder strips were lower than controls after tetrodotoxin (TTX, a sodium channel blocker that inhibits axonal action potentials). Yet, in all groups, epibatidine-induced strip contractions were similarly inhibited by mecamylamine and hexamethonium (ganglionic nicotinic receptor antagonists), SR 16584 (α3ß4 neuronal nicotinic receptor antagonist), atracurium and tubocurarine (neuromuscular nicotinic receptor antagonists), and atropine (muscarinic receptor antagonist), indicating that nicotinic receptors (particularly α3ß4 subtypes), neuromuscular and muscarinic receptors play roles in bladder contractility. In control bladder strips, since tetrodotoxin did not inhibit epibatidine contractions, nicotinic receptors are likely located on nerve terminals. The tetrodotoxin inhibition of epibatidine-induced contractions in Decentralized and ObNT-Reinn suggests a relocation of nicotinic receptors from nerve terminals to more distant axonal sites, perhaps as a compensatory mechanism to recover bladder function.

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 2: correlation between histological changes and nerve evoked contractions.

We determined the effect of pelvic organ decentralization and reinnervation 1 yr later on urinary bladder histology and function. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, eight were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers, then euthanized 8-12 mo later. Four served as long-term decentralized only animals. Before euthanasia, pelvic or transferred nerves and L1-S3 spinal roots were stimulated and maximum detrusor pressure (MDP) recorded. Bladder specimens were collected for histological and ex vivo smooth muscle contractility studies. Both reinnervated and decentralized animals showed less or denuded urothelium, fewer intramural ganglia, and more inflammation and collagen, than controls, although percent muscle was maintained. In reinnervated animals, pgp9.5+ axon density was higher compared with decentralized animals. Ex vivo smooth muscle contractions in response to KCl correlated positively with submucosal inflammation, detrusor muscle thickness, and pgp9.5+ axon density. In vivo, reinnervated animals showed higher MDP after stimulation of L1-L6 roots compared with their transected L7-S3 roots, and reinnervated and decentralized animals showed lower MDP than controls after stimulation of nerves (due likely to fibrotic nerve encapsulation). MDP correlated negatively with detrusor collagen and inflammation, and positively with pgp9.5+ axon density and intramural ganglia numbers. These results demonstrate that bladder function can be improved by transfer of obturator nerves to pelvic nerves at 1 yr after decentralization, although the fibrosis and inflammation that developed were associated with decreased contractile function.

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 1: attenuation of purinergic bladder smooth muscle contractions.

This study determined the effect of pelvic organ decentralization and reinnervation 1 yr later on the contribution of muscarinic and purinergic receptors to ex vivo, nerve-evoked, bladder smooth muscle contractions. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, 8 were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers then euthanized 8-12 mo later. Four served as long-term decentralized only animals. Controls included six sham-operated and three unoperated animals. Detrusor muscle was assessed for contractile responses to potassium chloride (KCl) and electric field stimulation (EFS) before and after purinergic receptor desensitization with α, ß-methylene adenosine triphosphate (α,ß-mATP), muscarinic receptor antagonism with atropine, or sodium channel blockade with tetrodotoxin. Atropine inhibition of EFS-induced contractions increased in decentralized and reinnervated animals compared with controls. Maximal contractile responses to α,ß-mATP did not differ between groups. In strips from decentralized and reinnervated animals, the contractile response to EFS was enhanced at lower frequencies compared with normal controls. The observation of increased blockade of nerve-evoked contractions by muscarinic antagonist with no change in responsiveness to purinergic agonist suggests either decreased ATP release or increased ecto-ATPase activity in detrusor muscle as a consequence of the long-term decentralization. The reduction in the frequency required to produce maximum contraction following decentralization may be due to enhanced nerve sensitivity to EFS or a change in the effectiveness of the neurotransmission.

Bladder reinnervation by somatic nerve transfer to pelvic nerve vesical branches does not reinnervate the urethra.

AIMS: We sought to determine whether somatic lumbar nerve transfer to the pelvic nerve's anterior vesical branch after sacral decentralization for detrusor muscle reinnervation also leads to aberrant innervation of the bladder outlet. METHODS: Twenty-six female mongrel hound dogs underwent transection of sacral dorsal and ventral spinal roots (ie, sacral decentralization). Immediately afterward, 12 received genitofemoral nerve transfer and 9 received femoral nerve branch transfer. Five were left sacrally decentralized. Controls included 3 sham-operated and 6 unoperated. Eight months postsurgery, the bladder and urethra were injected with retrograde tracing dyes cystoscopically. After 3 weeks, detrusor and urethral pressures were assayed electrophysiologically immediately before euthanasia and characterization of neural reinnervation. RESULTS: Electrical stimulation of spinal cords or roots did not lead to increased urethral sphincter pressure in nerve transfer animals, compared with decentralized animals, confirming a lack of functional reinnervation of the bladder outlet. In contrast, mean detrusor pressure increased after lumbar cord/root stimulation. In sham/unoperated animals, urethral and bladder dye injections resulted in labeled neurons in sacral level neural structures (dorsal root ganglia [DRG], sympathetic trunk ganglia [STG], and spinal cord ventral horns); labeling absent in decentralized animals. Urethral dye injections did not result in labeling in lumbar or sacral level neural structures in either nerve transfer group while bladder dye injections lead to increased labeled neurons in lumbar level DRG, STG, and ventral horns, compared to sacrally decentralized animals. CONCLUSION: Pelvic nerve transfer for bladder reinnervation does not impact urethral sphincter innervation.

Determining integrity of bladder innervation and smooth muscle function 1 year after lower spinal root transection in canines.

AIMS: To assess bladder smooth muscle function and innervation after long-term lower spinal root transection in canines. METHODS: Thirteen female mixed-breed hound dogs underwent bladder decentralization, which included transection of all sacral dorsal and ventral roots caudal to L7 and hypogastric nerves, bilaterally (n = 3); all sacral roots and hypogastric nerves plus transection of L7 dorsal roots, bilaterally (n = 4); or a sham operation (n = 6). At a year after initial surgery, bladder function was assessed in vivo by stimulation of the pelvic plexus. The bladder tissue was harvested for ex vivo smooth muscle contractility studies. Remaining bladder was evaluated for nerve morphology immunohistochemically using neuronal marker PGP9.5, apoptotic activity using terminal deoxynucleotidyl transferase dUTP nick end labeling, and histopathology using a hematoxylin and eosin stain. RESULTS: Sacral root decentralization did not reduce maximum strength of pelvic plexus stimulation-induced bladder contraction, although long-term sacral dorsal and ventral root plus L7 dorsal root transection significantly decreased contraction strength. Electric field stimulation-induced contractions of the detrusor from all decentralized animals were preserved, compared to controls. Viable nerves and intramural ganglia were visualized in the bladder wall, regardless of group. There was no difference in amount of apoptosis in bladder smooth muscle between groups. CONCLUSION: Bladder smooth muscle cells maintain their function after long-term bladder decentralization. While pelvic plexus-induced bladder contractions were less robust at 1 year after lower spinal root transection, the absence of atrophy and preservation of at least some nerve activity may allow for successful surgical reinnervation after long-term injury.

Evidence of vagus nerve sprouting to innervate the urinary bladder and clitoris in a canine model of lower motoneuron lesioned bladder.

AIMS: Complete spinal cord injury does not block perceptual responses or inferior solitary nucleus activation after genital self-stimulation, even though the vagus is not thought to innervate pelvic structures. We tested if vagus nerve endings sprout after bladder decentralization to innervate genitourinary structures in canines with decentralized bladders. METHODS: Four reinnervation surgeries were performed in female hounds: bilateral genitofemoral nerve transfer to pelvic nerve with vesicostomy (GNF-V) or without (GFN-NV); and left femoral nerve transfer (FNT-V and FNT-NV). After 8 months, retrograde dyes were injected into genitourinary structures. Three weeks later, at euthanasia, reinnervation was evaluated as increased detrusor pressure induced by functional electrical stimulation (FES). Controls included un-operated, sham-operated, and decentralized animals. RESULTS: Increased detrusor pressure was seen in 8/12 GFNT-V, 4/5 GFNT-NV, 5/5 FNT-V, and 4/5 FNT-NV animals after FES, but not decentralized controls. Lumbar cord segments contained cells labeled from the bladder in all nerve transfer animals with FES-induced increased detrusor pressure. Nodose ganglia cells labeled from the bladder were observed in 5/7 nerve transfer animals (1/2 GNT-NV; 4/5 FNT-V), and from the clitoris were in 6/7 nerve transfer animals (2/2 GFNT-NV; 4/5 FNT-V). Dorsal motor nucleus vagus cells labeled from the bladder were observed in 3/5 nerve transfer animals (1/2 GFNT-NV; 2/3 FNT-V), and from the clitoris in 4/5 nerve transfer animals (1/2 GFNT-NV; 3/3 FNT-V). Controls lacked this labeling. CONCLUSIONS: Evidence of vagal nerve sprouting to the bladder and clitoris was observed in canines with lower motoneuron lesioned bladders. Neurourol. Urodynam. 36:91-97, 2017. © 2015 Wiley Periodicals, Inc.

Analyzing cost-effectiveness of ulnar and median nerve transfers to regain forearm flexion.

OBJECTIVE Peripheral nerve transfers to regain elbow flexion via the ulnar nerve (Oberlin nerve transfer) and median nerves are surgical options that benefit patients. Prior studies have assessed the comparative effectiveness of ulnar and median nerve transfers for upper trunk brachial plexus injury, yet no study has examined the cost-effectiveness of this surgery to improve quality-adjusted life years (QALYs). The authors present a cost-effectiveness model of the Oberlin nerve transfer and median nerve transfer to restore elbow flexion in the adult population with upper brachial plexus injury. METHODS Using a Markov model, the authors simulated ulnar and median nerve transfers and conservative measures in terms of neurological recovery and improvements in quality of life (QOL) for patients with upper brachial plexus injury. Transition probabilities were collected from previous studies that assessed the surgical efficacy of ulnar and median nerve transfers, complication rates associated with comparable surgical interventions, and the natural history of conservative measures. Incremental cost-effectiveness ratios (ICERs), defined as cost in dollars per QALY, were calculated. Incremental cost-effectiveness ratios less than $50,000/QALY were considered cost-effective. One-way and 2-way sensitivity analyses were used to assess parameter uncertainty. Probabilistic sampling was used to assess ranges of outcomes across 100,000 trials. RESULTS The authors' base-case model demonstrated that ulnar and median nerve transfers, with an estimated cost of $5066.19, improved effectiveness by 0.79 QALY over a lifetime compared with conservative management. Without modeling the indirect cost due to loss of income over lifetime associated with elbow function loss, surgical treatment had an ICER of $6453.41/QALY gained. Factoring in the loss of income as indirect cost, surgical treatment had an ICER of -$96,755.42/QALY gained, demonstrating an overall lifetime cost savings due to increased probability of returning to work. One-way sensitivity analysis demonstrated that the model was most sensitive to assumptions about cost of surgery, probability of good surgical outcome, and spontaneous recovery of neurological function with conservative treatment. Two-way sensitivity analysis demonstrated that surgical intervention was cost-effective with an ICER of $18,828.06/QALY even with the authors' most conservative parameters with surgical costs at $50,000 and probability of success of 50% when considering the potential income recovered through returning to work. Probabilistic sampling demonstrated that surgical intervention was cost-effective in 76% of cases at a willingness-to-pay threshold of $50,000/QALY gained. CONCLUSIONS The authors' model demonstrates that ulnar and median nerve transfers for upper brachial plexus injury improves QALY in a cost-effective manner.

A neurophysiological approach to nerve transfer to restore upper limb function in cervical spinal cord injury.

A successful nerve transfer surgery can provide a wealth of benefits to a patient with cervical spinal cord injury. The process of surgical decision making ideally uses all pertinent information to produce the best functional outcome. Reliance on clinical examination and imaging studies alone can miss valuable information on the state of spinal cord health. In this regard, neurophysiological evaluation has the potential to effectively gauge the neurological status of even select pools of anterior horn cells and their axons to small nerve branches in question to determine the potential efficacy of their use in a transfer. If available preoperatively, knowledge gained from such an evaluation could significantly alter the reconstructive surgical plan and avoid poor results. The authors describe their institution's approach to the assessment of patients with cervical spinal cord injury who are being considered for nerve transfer surgery in both the acute and chronic setting and broadly review the neurophysiological techniques used.

Establishing reconstructive neurosurgery as a subspecialty.

Neurosurgery is experiencing the emergence of a new subspecialty focused on function restoration. New, evolving, and reappraised surgical procedures have provided an opportunity to restore function to many patients with previously undertreated disorders. Candidates for reconstruction were previously limited to those with peripheral nerve and brachial plexus injuries, but this has been expanded to include stroke, spinal cord injury, and a host of other paralyzing disorders affecting both upper and lower motor neurons. Similar to the recent evolution of the well-established subdisciplines of spinal and vascular neurosurgery, reconstructive neurosurgery requires the adaptation of techniques and skills that were not traditionally a part of neurosurgical training. Neurosurgeons-as the specialists who already manage this patient population and possess the requisite surgical skills to master the required techniques-have a unique opportunity to lead the development of this field. The full development of this subspecialty will lay the foundation for the subsequent addition of emerging treatments, such as neuroprosthetics and stem cell-based interventions. As such, reconstructive neurosurgery represents an important aspect of neurosurgical training that can ameliorate many of the deficits encountered in the traditional practice of neurosurgery.

Nerve transfer versus muscle transfer to restore elbow flexion after pan-brachial plexus injury: a cost-effectiveness analysis.

OBJECTIVE Pan-brachial plexus injury (PBPI), involving C5-T1, disproportionately affects young males, causing lifelong disability and decreased quality of life. The restoration of elbow flexion remains a surgical priority for these patients. Within the first 6 months of injury, transfer of spinal accessory nerve (SAN) fascicles via a sural nerve graft or intercostal nerve (ICN) fascicles to the musculocutaneous nerve can restore elbow flexion. Beyond 1 year, free-functioning muscle transplantation (FFMT) of the gracilis muscle can be used to restore elbow flexion. The authors present the first cost-effectiveness model to directly compare the different treatment strategies available to a patient with PBPI. This model assesses the quality of life impact, surgical costs, and possible income recovered through restoration of elbow flexion. METHODS A Markov model was constructed to simulate a 25-year-old man with PBPI without signs of recovery 4.5 months after injury. The management options available to the patient were SAN transfer, ICN transfer, delayed FFMT, or no treatment. Probabilities of surgical success rates, quality of life measurements, and disability were derived from the published literature. Cost-effectiveness was defined using incremental cost-effectiveness ratios (ICERs) defined by the ratio between costs of a treatment strategy and quality-adjusted life years (QALYs) gained. A strategy was considered cost-effective if it yielded an ICER less than a willingness-to-pay of $50,000/QALY gained. Probabilistic sensitivity analysis (PSA) was performed to address parameter uncertainty. RESULTS The base case model demonstrated a lifetime QALYs of 22.45 in the SAN group, 22.0 in the ICN group, 22.3 in the FFMT group, and 21.3 in the no-treatment group. The lifetime costs of income lost through disability and interventional/rehabilitation costs were $683,400 in the SAN group, $727,400 in the ICN group, $704,900 in the FFMT group, and $783,700 in the no-treatment group. Each of the interventional modalities was able to dramatically improve quality of life and decrease lifelong costs. A Monte Carlo PSA demonstrated that at a willingness-to-pay of $50,000/QALY gained, SAN transfer dominated in 88.5% of iterations, FFMT dominated in 7.5% of iterations, ICN dominated in 3.5% of iterations, and no treatment dominated in 0.5% of iterations. CONCLUSIONS This model demonstrates that nerve transfer surgery and muscle transplantation are cost-effective strategies in the management of PBPI. These reconstructive neurosurgical modalities can improve quality of life and lifelong earnings through decreasing disability.

Contralateral C-7 transfer: is direct repair really superior to grafting?

It is not uncommon for a severe traumatic brachial plexus injury to involve all 5 roots, resulting in a flail upper limb. In such cases, surgical reconstruction is often palliative, providing only rudimentary function. Nerve transfers are the mainstay of reconstructive strategies due to the predominance of root avulsions. Consistent results are obtained only for restoration of shoulder stability and elbow flexion, whereas restoring useful hand function remains a challenge. The transfer of the contralateral C-7 (cC-7) is commonly used in an attempt to restore basic hand function, but results are notoriously unreliable and inconsistent. Shu-feng Wang and colleagues recently proposed a potentially more successful permutation of this procedure. They advocated direct approximation of the cC-7 to the lower trunk on the paralyzed side, thus avoiding the interposition of nerve grafts. This technique involves a lengthy dissection of the cC-7 transfer across the midline via a prespinal route, as well as extensive mobilization of the ipsilateral lower trunk by cutting a subset of its branches, adducting the arm, and (if necessary) shortening the humerus. Each of these steps is indispensable to achieve direct approximation of the nerve ends. Many surgeons have tried to emulate Wang's strategy. However, the technical difficulties involved have forced recourse to interposition of nerve grafts once again. The authors report their observations in the first 22 patients in whom they performed this procedure. Direct cC-7 repair via the prespinal route was performed in 12 patients. Shortening of the humerus was necessary in 9 of these 12 patients. In 10 patients, a direct repair was not feasible and nerve grafting was performed. The median follow-up period was 26 months for the direct coaptation group and 28.5 months for the nerve graft group. In the direct repair group, 10 of the 12 patients regained Medical Research Council Grade 3 flexion of the wrist and of the middle, ring, and little fingers, while the remaining 2 patients had Grade 2 function. Flexion appeared 12-14 months after the operation. At the latest follow-up, these patients could activate the wrist and hand without requiring significant augmentation maneuvers in the donor limb. In contrast, repair requiring interposition grafts resulted in Grade 3 strength in only 2 of 10 patients, while 7 had Grade 2 strength, and 1 experienced failure. In all grafted cases, the patient had to forcibly contract the contralateral pectoralis major and triceps muscles to produce the weak movements on the reconstructed side. In this small series, the authors demonstrated a distinct advantage associated with the avoidance of grafts when transferring the cC-7 to restore hand function. The authors conclude that efforts to achieve direct approximation of the donor C-7 and the recipient lower trunk are necessary and justified.

Heterozygous congenital Factor VII deficiency with the 9729del4 mutation, associated with severe spontaneous intracranial bleeding in an adolescent male.

BACKGROUND: In congenital Factor (F) VII deficiency bleeding phenotype and intrinsic FVII activity levels don't always correlate. Patients with FVII activity levels <30% appear to have a higher bleeding propensity, but bleeding can also occur at higher FVII activity levels. Reasons for bleeding at higher FVII activity levels are unknown, and it remains challenging to manage such patients clinically. CASE: A 19year old male with spontaneous intracranial hemorrhage and FVII activity levels of 44%, requiring emergent surgical intervention and a strategy for FVII replacement. Genotyping showed the rare heterozygous FVII 9729del4 mutation. Bleed evacuation was complicated by epidural abscess requiring craniectomy, bone graft procedures, and prolonged administration of recombinant human (rh) activated FVII (FVIIa). The patient recovered without neurological deficits, and remains on prophylactic low dose treatment with rhFVIIa in relation to risky athletic activities. CONCLUSION: For clinicians, it is important to recognize that effects of rhFVIIa within these pathways are independent of its contribution to blood clot formation and cannot be assessed by clotting assays. Reduced FVII levels should therefore not be dismissed, as even a mild reduction may result in spontaneous bleeding. Treatment of mild FVII deficiency requires a careful case-by-case approach, based on the clinical scenario.

Neuromuscular nicotinic receptors mediate bladder contractions following bladder reinnervation with somatic to autonomic nerve transfer after decentralization by spinal root transection.

PURPOSE: We investigated whether the reinnervated neuronal pathway mediates contraction via the same neurotransmitter and receptor mechanisms as the original pathway. MATERIALS AND METHODS: After decentralizing the bladder by transecting the sacral roots in dogs we performed peripheral nerve transfer, including bilateral genitofemoral to pelvic nerve transfer and unilateral left femoral nerve to bilateral pelvic nerve transfer. Reinnervation was assessed 7.5 months postoperatively by monitoring bladder pressure during electrical stimulation of the transferred nerves, spinal ventral roots and spinal cord. RESULTS: Of the 17 dogs with genitofemoral to pelvic nerve transfer 14 (82%) demonstrated functional bladder reinnervation as evidenced by increased bladder pressure during stimulation of the transferred genitofemoral nerve, or L3 or L4 spinal ventral roots. Lumbar spinal cord stimulation caused increased bladder pressure in 9 of 10 dogs (90%) with unilateral left femoral nerve to bilateral pelvic nerve transfer. Succinylcholine virtually eliminated the bladder pressure increases induced by electrical stimulation of the transferred somatic nerves or of the lumbar spinal segments that contribute axons to these donor nerves. In unoperated or sham operated controls succinylcholine had no effect on nerve evoked bladder pressure increases but it substantially decreased the urethral and anal sphincter pressure induced by stimulating the lumbosacral spinal cord or the S2-S3 spinal ventral roots. The reinnervated detrusor muscles of dogs with genitofemoral to pelvic nerve transfer and unilateral left femoral nerve to bilateral pelvic nerve transfer also showed increased α1 nicotinic receptor subunit immunoreactivity in punctate dots on detrusor muscle fascicles and in neuronal cell bodies. This staining was not observed in controls. CONCLUSIONS: Succinylcholine sensitive nicotinic receptors, which normally mediate only skeletal muscle neuromuscular junction neurotransmission, appeared in the new neuronal pathway after genitofemoral to pelvic and unilateral femoral nerve to bilateral pelvic nerve transfer. This suggests end organ neuroplasticity after reinnervation by somatic motor axons.

Bladder reinnervation using a primarily motor donor nerve (femoral nerve branches) is functionally superior to using a primarily sensory donor nerve (genitofemoral nerve).

PURPOSE: We determined whether transfer of a primarily motor nerve (femoral) to the anterior vesicle branch of the pelvic nerve would allow for more effective bladder reinnervation than transfer of a primarily sensory nerve (genitofemoral). MATERIALS AND METHODS: A total of 41 female mongrel dogs underwent bladder decentralization and then bilateral nerve transfer, or served as sham operated or unoperated controls. Decentralization was achieved by bilateral transection of all sacral roots that induced bladder contraction upon electrical stimulation. Retrograde neuronal labeling dye was injected in the bladder 3 weeks before sacrifice. RESULTS: Increased detrusor pressure after direct stimulation of the transferred nerve, lumbar spinal cord or spinal root was observed in 12 of 17 dogs with genitofemoral nerve transfer and in 9 of 10 with femoral nerve transfer (mean ± SEM 7.6 ± 1.4 and 11.7 ± 3.1 cm H2O, respectively). Mean detrusor pressure after direct electrical stimulation of transferred femoral nerves was statistically significantly greater than after stimulation of transferred genitofemoral nerves. Retrograde labeled neurons from the bladder observed in upper lumbar cord segments after genitofemoral and femoral nerve transfer confirmed bladder reinnervation, as did labeled axons at the nerve transfer site. CONCLUSIONS: While transfer of a mixed sensory and motor nerve (genitofemoral) or a primarily motor nerve (femoral) can reinnervate the bladder, using the primarily motor nerve provided greater return of nerve evoked detrusor contraction. This surgical approach may be useful to achieve bladder emptying in patients with lower motor spinal cord injury.

Atom interferometry in an optical cavity.

We propose and demonstrate a new scheme for atom interferometry, using light pulses inside an optical cavity as matter wave beam splitters. The cavity provides power enhancement, spatial filtering, and a precise beam geometry, enabling new techniques such as low power beam splitters (<100 µW), large momentum transfer beam splitters with modest power, or new self-aligned interferometer geometries utilizing the transverse modes of the optical cavity. As a first demonstration, we obtain Ramsey-Raman fringes with >75% contrast and measure the acceleration due to gravity, g, to 60 µg/sqrt[Hz] resolution in a Mach-Zehnder geometry. We use >10(7) cesium atoms in the compact mode volume (600 µm 1/e(2) waist) of the cavity and show trapping of atoms in higher transverse modes. This work paves the way toward compact, high sensitivity, multiaxis interferometry.

Robot-assisted triple neurectomy for iatrogenic inguinal pain: a technical note.

BACKGROUND: Painful neuromas are a relatively common complication of hernia and abdominal wall surgery. OBJECTIVE: Surgical neurectomy has the potential to to provide durable relief for chronic pain; however, current surgical approaches are not without morbidity or anatomical challenges.We sought a surgical alternative. METHODS: In the treatment of a case of incapacitating inguinal pain, we performed an anterior transperitoneal approach using a surgical robot. RESULTS: This approach was facile and provided elegant anatomical visualization. CONCLUSION: This case describes the first known robot-assisted laparoscopic triple neurectomy and details a simplified, transperitoneal approach.

Supinator to Posterior Interosseous Nerve Transfer for Recovery of Hand Opening in the Tetraplegic Patient: A Case Series.

BACKGROUND AND OBJECTIVES: Cervical spinal cord injury results in devastating loss of function. Nerve transfers can restore functional use of the hand, the highest priority function in this population to gain independence. Transfer of radial nerve branches innervating the supinator to the posterior interosseous nerve (SUP-PIN) has become a primary intervention for the recovery of hand opening, but few outcome reports exist to date. We report single-surgeon outcomes for this procedure. METHODS: The SUP-PIN transfer was performed on adults with traumatic spinal cord injury resulting in hand paralysis. Outcome measures include Medical Research Council strength grade for extension of each digit, and angles representing critical apertures: the first web space opening of the thumb, and metacarpophalangeal angle of the remaining fingers. Factors affecting these measurements, including preserved tone and spasticity of related muscles, were also assessed. RESULTS: Twenty-three adult patients with a C5-7 motor level underwent SUP-PIN transfers on 36 limbs (median age 31 years, interquartile range [21.5, 41]). The median interval from injury to surgery was 10.5 (8.2, 6.5) months, with 9 (7.5, 11) months for the acute injuries and 50 (32, 66) months for the chronic (>18 months) injuries. Outcomes were observed at a mean follow-up of 22 (14, 32.5) months. 30 (83.3%) hands recovered at least antigravity extension of the thumb and 34 (94.4%) demonstrated successful antigravity strength for the finger extensors, providing adequate opening for a functional grasp. Chronic patients (>18 months after injury) showed similar outcomes to those who had earlier surgery. Supination remained strong (at least M4) in all but a single patient and no complications were observed. CONCLUSION: SUP-PIN is a reliable procedure for recovery of finger extension. Chronic patients remain good candidates, provided innervation of target muscles is preserved. Higher C5 injuries were more likely to have poor outcomes.

Anatomical Location of the Vesical Branches of the Inferior Hypogastric Plexus in Human Cadavers.

We have demonstrated in canines that somatic nerve transfer to vesical branches of the inferior hypogastric plexus (IHP) can be used for bladder reinnervation after spinal root injury. Yet, the complex anatomy of the IHP hinders the clinical application of this repair strategy. Here, using human cadavers, we clarify the spatial relationships of the vesical branches of the IHP and nearby pelvic ganglia, with the ureteral orifice of the bladder. Forty-four pelvic regions were examined in 30 human cadavers. Gross post-mortem and intra-operative approaches (open anterior abdominal, manual laparoscopic, and robot-assisted) were used. Nerve branch distances and diameters were measured after thorough visual inspection and gentle dissection, so as to not distort tissue. The IHP had between 1 to 4 vesical branches (2.33 ± 0.72, mean ± SD) with average diameters of 0.51 ± 0.06 mm. Vesical branches from the IHP arose from a grossly visible pelvic ganglion in 93% of cases (confirmed histologically). The pelvic ganglion was typically located 7.11 ± 6.11 mm posterolateral to the ureteral orifice in 69% of specimens. With this in-depth characterization, vesical branches from the IHP can be safely located both posterolateral to the ureteral orifice and emanating from a more proximal ganglionic enlargement during surgical procedures.