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Neurophysiological testing of the pelvic floor is recognized as an essential tool to identify pathophysiological mechanisms of pelvic floor disorders, support clinical diagnosis, and aid in therapeutic decisions. Nevertheless, the diagnostic value of these tests in specific neurological diseases of the pelvic floor is not completely clarified. Seeking to fill this gap, the members of the Neurophysiology of the Pelvic Floor Study Group of the Italian Clinical Neurophysiology Society performed a systematic review of the literature to gather available evidence for and against the utility of neurophysiological tests. Our findings confirm the utility of some tests in specific clinical conditions [e.g. concentric needle electromyography, evaluation of sacral reflexes and of pudendal somatosensory evoked potentials (pSEPs) in cauda equina and conus medullaris lesions, and evaluation of pSEPs and perineal sympathetic skin response in spinal cord lesions], and support their use in clinical practice. Other tests, particularly those not currently supported by high-level evidence, when employed in individual patients, should be evaluated in the overall clinical context, or otherwise used for research purposes.

Peripheral nervous system injury is a frequent traumatic event, affecting a growing field of population, according to the change in lifestyle. Nerve autograph is still the golden standard, however it is invasive and limited in terms of amount and dimension of the available source. Various alternative therapeutic approaches have been proposed and results have been, so far, inconsistent, in terms of both quality and extent of nerve regeneration and re-innervation. Here, a novel technique is presented able to produce tubular collagen-based scaffolds, characterized by a radially/axially patterned microporosity (MPCS). The process has been modelled by means of the Lamm differential equation, according to appropriate scaling laws. In the present investigation, we tested in vivo the clinico-pathological impact of this MPCS over a 10-mm critical size defects in the adult rat sciatic nerve. Rats with transection of the sciatic nerve and implanted with either commercial collagen or silicon conduits were used as controls. MPCS-implanted rats showed significantly improved nerve regeneration at both neurophysiological and neuropathological levels, as compared to control rats. Our data demonstrate that this specific tubular scaffold micro-patterning orchestrates physiological regeneration in the adult rat sciatic nerve over a 10-mm critical size defect. Indeed, whole genome gene expression analyses confirm that the MPCS induces selective gene expression patterns and enhanced cells proliferation, motility and myelination, with a remarkable cell-instructing behavior. The development of morphogenesis phenomena during nerve regeneration process opens new perspectives towards the clinical application of MPCS in this field, owing to its ease of production, cost-effectiveness, favorable degradation rate and remarkable cell-instructing behavior.

Introduction Nerve injury is a frequent event especially after traumatic lesion, affecting mainly young people. Various therapeutic approaches have been proposed for patients suffering from peripheral nerve injuries. Despite the significant increase in the understanding of the pathophysiology of nerve, results have been, so far, inconsistent, in terms of both quality as well as extent of nerve regeneration and re-innervation. The use of a conduit to reconnect the proximal and distal stumps of a transected nerve and induce peripheral nervous system (PNS) regeneration has been the subject of a large number of investigations. While it is quite established that the presence of a conduit between the transected stumps allows PNS regeneration [1], the micro-structural, mechanical and compositional features of the conduit, as any material inserted within, might significantly affect the quality of regeneration [2, 3]. We have previously developed a micro-patterned collagen scaffold (MPCS), by a spinning technique [4], with a peculiar radially aligned porosity of the tube wall, and predicted that its microstructure might play a significant role in the regulation of cellular and molecular mechanisms sustaining cell behaviour inside the scaffold and, in turn, improving distal induced regeneration. In this work the clinico-pathological impact of this MPCS was evaluated in the adult rat sciatic nerve. Neurophysiological, morphological and whole genome expression studies were conducted to assess the major pathways regulating nerve development and morphogenesis. Materials & Methods A complete and detailed description of the process adopted to produce MPCS has been reported [4]. Scaffolds are prepared using a collagen-based slurry; spinning of the slurry in a proper apparatus and rapid freezing of the sedimented suspension in liquid nitrogen; freeze-drying of the solidified suspension to obtain the final MPCS. Nerve regeneration in MPCS-implanted transected rats was evaluated in vivo over a 10-mm critical size defect in the adult rat sciatic nerve. Rats with transection of the sciatic nerve and implanted with either commercial collagen (NeuraGen®) or silicon conduits were used as controls. To evaluate the degree of regeneration and re-myelination after nerve transection, neurophysiological and morphological studies were performed. Together with sciatic nerves, the tibial plantar nerves at the paw were also investigated, to establish the process of re-innervation at the distal part. Whole gene expression (GE) profiling studies on injured sciatic nerve rats were conducted to investigate the molecular changes and the regulation of biological processes provided by our MPCS. Results & Discussion A damage, which determines a detachment of two nerve stumps, like a traumatic lesion, needs a device that creates an ideal micro-environment in order to facilitate axonal regeneration and re-myelination. Thus, we have developed a MPCS under the hypothesis that the micro-structure of the wall conduit could create a favourable micro-environment for full nerve regeneration after experimental transection. Neurophysiological and morphological studies suggested a faster functional nerve recovery of MPCS-implanted rats compared to rats treated with other conduits, as well as a prompt restoration of a functional vasculature with a physiological blood-nerve barrier. Moreover, in the MPCS, the long-term analysis showed a normal development of nerve, consisting of normal axon diameters and myelin thickness. Up-regulation of the myelin specific-gene observed at early time only on MPCS suggested the ability of our scaffold in providing clues for Schwann cell differentiation. Whole genome gene expression analyses further confirmed that the MPCS induces selective gene expression patterns and enhanced cells proliferation, motility and myelination. Conclusion Our findings provide remarkable molecular and ultra-structural evidence that the optimal micro-patterning of the proposed collagen scaffold plays a key role in turning the inner micro-environment into hospitable for development, rather than induced regeneration, of the proximal nerve stump. Within these optimal conditions, the transected nerve recapitulates in a coordinated fashion its innate programs of differentiation, which ultimately lead to progressive substitution of non-neuronal with neuronal tissues. We hypothesize that the radially aligned porosity of the MPCS promotes nerve regeneration by inducing morphogenetic stimuli and orchestrating cell behaviour towards a physiological regeneration mode.

Objective To investigate the timing, course, and clinical characteristics of the response to intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Design Data were extracted from the ICE trial, a randomized, double-blind, placebo-controlled trial of immune globulin intravenous, 10% caprylate/chromatography purified (IGIV-C). Setting Multiple international centers. Participants One hundred seventeen individuals with CIDP. Intervention Treatment with IGIV-C (Gamunex, n = 59) or placebo (n = 58), with IGIV-C administered as a 2-g/kg loading dose followed by a 1-g/kg maintenance dose every 3 weeks, for up to 24 weeks. Main Outcome Measures The primary efficacy parameter was an improvement of 1 or more points in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Participants treated with IGIV-C were divided into subgroups based on meeting responder vs nonresponder definitions and by time to first improvement. Results Among 30 responders to IGIV-C, 14 (47%) patients had improved adjusted INCAT scores by week 3, and 16 (53%) patients improved at week 6 after a second infusion. Participants who improved by week 3 were more severely disabled at baseline than those who improved at 6 weeks. In patients who improved, the number of individuals reaching maximal improvement continued to increase during maintenance therapy for up to 24 weeks. For patients with first improvement by week 3, the change in dominant-hand grip strength over time tended to parallel the INCAT score. In patients with first improvement by week 6, however, the improvement in dominant-hand grip strength preceded initial improvement in INCAT score. Conclusions Data suggest that treatment with 2 courses of IGIV-C administered 3 weeks apart may be required for initial improvement, and continued maintenance therapy may be necessary to achieve a maximal therapeutic response. Trial Registration clinicaltrials.gov Identifier:NCT00220740

The aim of this work is to assess the clinical and functional outcome of patients who underwent different types of neck dissection, with special regards to the spinal accessory nerve, trapezius muscle and shoulder function. From February 2008 to July 2010, we evaluated 17 cases of neck dissection in patients affected by laryngeal carcinoma clinically staged N0. We performed selective neck dissection (IIA-IIBIII- IV) in 11 cases (group A) and superselective neck dissection in 6 cases (group B). All patients underwent clinical examination before surgery to evaluate shoulder function. They also underwent functional evaluation of the spinal accessory nerve through electromyography (study of muscular activity) and electroneurography (study of motor action potential). Patients were evaluated before surgery (T0), 8 days after surgery (T1) and 21 days after surgery (T2). In all cases, at the end of surgery it was possible to assess the integrity of the spinal accessory nerve. The average value of the MAP was 13.06 in group A and 10.98 in group B at T0. Eight days after surgery (T1) the value of MAP was reduced to 1.35 in group A and 6.15 in group B. Electromyography evaluation showed signs of denervation in 6 cases in group A and in 2 cases in group B. Voluntary activity was not detectable in 6 cases in group A, while it was present, even if reduced, in all cases in group B. At 21 days after surgery (T2), we found a value of MAP of 1.03 in group A and 6.43 in group B. Electromyography showed signs of denervation in 10 patients in group A and in 3 cases in group B. Voluntary activity was not detectable in 10 cases in group A, while it was present in all cases in group B. The arm abduction test was 2.5 in group A and 4.0 in group B. Neck dissection quality of life questionnaire showed a value of 24.17 in group A and a value of 25.5 in group B. Our data thus confirm that surgical manipulation of the nerve may be associated with severe impairment of nerve conduction when sublevel IIB is involved in the dissection.RIASSUNTOScopo di questo lavoro è stato valutare l'outcome clinico e funzionale di pazienti sottoposti a svuotamento linfonodale laterocervicale per tumori laringei in stadio clinico N0. In particolare l'attenzione è stata focalizzata sul nervo accessorio spinale e sulla funzionalità della spalla. Da Febbraio 2008 a Luglio 2010 sono stati studiati 17 casi di svuotamento linfonodale laterocervicale; in 11 casi è stato eseguito uno svuotamento selettivo (livelli IIA-IIB-III-IV)(gruppo A) e in 6 casi uno svuotamento superselettivo (livelli IIA-III-IV) (gruppo B). I pazienti sono stati valutati prima dell'intervento (T0) con un test clinico e con uno studio elettroneurografico (valutazione dell'attività muscolare) ed elettromiografico (studio del potenziale d'azione motorio). Quest'ultimo è stato ripetuto a 8 giorni (T1) e a 21 giorni (T2) dall'intervento. Una valutazione clinica è stata effettuata a distanza di un mese mediante il "neck dissection quality of life questionnaire" e l'"Arm abduction test". Nello studio elettroneurografico a T0 il valore medio del potenziale d'azione motorio (MAP) è risultato 13,06 nel gruppo A e 10,98 nel gruppo B. A T1 il MAP risultava 1,35 nel gruppo A e 6,15 nel gruppo B. Lo studio elettromiografico ha mostrato segni di denervazione in 6 casi del gruppo A e in 2 casi del gruppo B. L'attività volontaria non era registrabile in 6 casi del gruppo A mentre era presente, seppur ridotta, in tutti i casi del gruppo B. A T2 il valore del MAP è risultato di 1,03 nel gruppo A e di 6,43 nel gruppo B. L'elettromiografia ha confermato i segni di denervazione in 10 casi del gruppo A e in 3 casi del gruppo B. L'attività volontaria non era registrabile in 10 casi del gruppo A ed era invece presente in tutti i casi del gruppo B. L'"arm abduction" test è risultato di 2,5 nel gruppo A e 4 nel gruppo B. Il "Neck dissection quality of life questionnaire" ha mostrato un valore di 24,17 nel gruppo A e di 25,5 nel gruppo B. I nostri dati confermano che la manipolazione chirurgica del nervo accessorio può determinare una severa disfunzione quando il sottolivello IIB è compreso nella dissezione.

The peripheral nervous system (PNS) can regener- ate after injury but to fill a gap it needs to find a proper guide directing the axonal elongation. Many techni- ques and devices have been studied in order to pro- mote nerve regeneration but are still inadequate. The aim of this work is to validate an innovative high poros- ity collagen tube (medical devices, MD) in order to induce nerve regeneration in a 10-mm gap in the adult rat sciatic nerve. Nerves were retrieved for morpholog- ical and ultrastructural analysis at 8, 15, 30, 40 and 54, 90 and 120 days postoperatively and analyzed at differ- ent levels. Nerve conduction studies were also evalu- ated. At 8 days postoperatively fibroblast activation and extracellular matrix reorganization were already evident associated with a great number of mature endoneurial neovessels with tight junctions. In the fol- lowing time points an active process of axonal regen- eration was documented; after two months we showed, in the regenerated mid-graft, a normal num- ber of well myelinated axons with normal G-ratio and definite signs of reinnervation in the tibial and peroneal branch. No inflammatory cells were evident. Electro- physiological assessment showed a motor action potential at 90 days postoperatively distally, recordable at the paw. Overall, the neurophysiological and neuro- pathological data demonstrate the terrific quality of nerve regeneration using our MD which performs bet- ter in comparison to the collagen already available in clinical practice and the silicone tubes, used as a con- trol. These results make us confident in proposing our MD in clinical practice to treat injury of the PNS.

Bridging the gap after a nerve transection has always been a top challenge in the field of neuroscience. The peripheral nervous system can regenerate after injury but to fill a gap needs to find a proper guide directing the axonal elongation. Many techniques and devices have been studied in order to promote nerve regeneration but are still inade- quate. The aim of this work is validating an innovative high porosity collagen tube (medical devices, MD) and comparing the nerve outgrowth through this MD to the already avail- able in clinical practice NeuroGen IntegraÒ collagen and the silicone tubes, as a standard control, in an animal model of traumatic injury. The conduits were implanted in a 10 mm- gap in rat sciatic nerve and retrieved at different time points for morphological and ultrastructural analysis. Nerve conduc- tion studies were also evaluated. Nerve outgrowth through the NeuroGen IntegraÒ devices appeared to be similar to the one in the silicone tubes, being characterized by mini- fascicles containing less small axons with thin myelin and without a well-organized blood vessels distribution in the en- doneurium. In contrast, our MD showed, in the regenerated mid-graft, a normal size and number of nerve fibers with a normal myelination (G-ratio), already evident at 60 days postoperatively. Moreover, perineurium and blood vessels appeared absolutely normal with tight junction by EM. At 90 days postoperatively a nerve action potential was recordable distally, at the paw, in the sciatic nerves of the rats implanted with our MD or with the NeuroGen ones whereas was absent in the silicon group. Overall the neurophysiologi- cal and neuropathological data demonstrate the terrific qual- ity of nerve regeneration using our MD. These results make us confident in proposing our MD in the clinical practice to treat injury of the PNS.

The main functional factors related to lifelong premature ejaculation (PE) etiology have been suggested to be penile hypersensitivity, greater cortical penile representation, and disturbance of central serotoninergic neurotransmission. To quantitatively assess penile sensory thresholds in European Caucasian patients with lifelong PE using the Genito-Sensory Analyzer (GSA, Medoc, Ramat Yishai, Israel) as compared with those of an age-comparable sample of volunteers without any ejaculatory compliant. Forty-two consecutive right-handed, fully potent patients with lifelong PE and 41 right-handed, fully potent, age-comparable volunteers with normal ejaculatory function were enrolled. Each man was assessed via comprehensive medical and sexual history; detailed physical examination; subjective scoring of sexual symptoms with the International Index of Erectile Function; and four consecutive measurements of intravaginal ejaculatory latency time with the stopwatch method. All men completed a detailed genital sensory evaluation using the GSA; thermal and vibratory sensation thresholds were computed at the pulp of the right index finger, and lateral aspect of penile shaft and glans, bilaterally. Comparing quantitatively assessed penile thermal and vibratory sensory thresholds between men with lifelong PE and controls without any ejaculatory compliant. Patients showed significantly higher (P < 0.001) thresholds at the right index finger but similar penile and glans thresholds for warm sensation as compared with controls. Cold sensation thresholds were not significantly different between groups at the right index finger or penile shaft, but glans thresholds for cold sensation were bilaterally significantly lower (P = 0.01) in patients. Patients showed significantly higher (all P