Enriching new transplantable RGC-like cells from retinal organoids for RGC replacement therapy.

Optic neuropathies, such as glaucoma, are due to progressive retinal ganglion cells (RGCs) degeneration, result in irreversible vision loss. The promising RGCs replacement therapy for restoring vision are impeded by insufficient RGC-like cells sources. The present work was enriched one new type RGC-like cells using two surface markers CD184 and CD171 from human induced pluripotent stem cells (hiPSCs) by FACS sorting firstly. These new kind cells have well proliferation ability and possessed passage tolerance in vitro 2D or 3D spheroids culture, which kept expressing Pax6, Brn3b and ßIII-Tubulin and so on. The transplanted CD184+CD171+ RGC-like cells could survive and integrate into the normal and optic nerve crush (ONC) mice retina, especially they were more inclined to across the optic nerve head and extend to the damaged optic nerve. These data support the feasible application for cell replacement therapy in RGC degenerative diseases, as well as help to develop new commercial cells sorting reagents and establish good manufacturing practice (GMP) grade RGC-like donor cells for further clinical application.

Reversal of injury-associated retinal ganglion cell gene expression by a phosphodiesterase anchoring disruptor peptide.

Loss of retinal ganglion cells (RGCs) is central to the pathogenesis of optic neuropathies such as glaucoma. Increased RGC cAMP signaling is neuroprotective. We have shown that displacement of the cAMP-specific phosphodiesterase PDE4D3 from an RGC perinuclear compartment by expression of the modified PDE4D3 N-terminal peptide 4D3(E) increases perinuclear cAMP and protein kinase A activity in cultured neurons and in vivo RGC survival after optic nerve crush (ONC) injury. To explore mechanisms by which PDE4D3 displacement promotes neuroprotection, in this study mice intravitreally injected with an adeno-associated virus to express an mCherry-tagged 4D3(E) peptide were subjected to ONC injury and analyzed by single cell RNA-sequencing (scRNA-seq). 4D3(E)-mCherry expression was associated with an attenuation of injury-induced changes in gene expression, thereby supporting the hypothesis that enhanced perinuclear PKA signaling promotes neuroprotective RGC gene expression.

The Pulsed Nd:YAG Laser Therapy Enhanced Nerve Regeneration via Apoptosis Inhibition in a Rat Crushed Sciatic Nerve Model.

The study was aimed to validate the efficacy of the pulsed Nd:YAG laser on nerve regeneration in a rat sciatic nerve crushed model. 54 Wistar rats were randomly assigned into three groups: shame control, crush control, and laser treated group. For the laser treated group, the pulsed Nd:YAG laser (10 Hz) with 350 mJ per pulse in energy density and 50 J/cm2 in fluence was applied extracorporeally at the lesion site for 12 min to daily deliver 500 J immediately and consecutive 9 days following the crush injury. At week 1, the apoptosis-related activities in the injured nerve were examined (n = 8/each group). The sciatic functional index (SFI) was measured preoperatively and weekly until 4 weeks after the index procedure. The injured nerve and the innervated gastrocnemius muscle histology were assessed at week 4 (n = 10/each group). At week 1, the laser group showed the significant less TUNEL-positive ratio (P < 0.05), and the lower expression of cleaved caspase3/procaspase-3 and beclin-2/beclin-2-associated protein X ratios compared with the crush control. Furthermore, the laser group revealed significantly better SFI since week 1 and throughout the study (P < 0.05, all) compared with the crush control. At week 4, the laser group showed significantly higher axon density, lower myelin g-ratio, and the corresponding higher glycogen expression (P < 0.05, all) in the gastrocnemius muscle compared with those in the crush control. The pulsed Nd:YAG might enhance the injured nerve regeneration via apoptosis inhibition.

Evaluation of the regeneration process of the sciatic nerve of a mouse animal model after application of freezing, crushing or electrocoagulation damage / Ocena procesu regeneracji nerwu kulszowego mysiego modelu zwierzecego po zastosowaniu uszkodzenia metoda mrozenia, zmiazdzenia i elektrokoagulacji.

The problem of regeneration of damaged peripheral nerves is an ongoing topic and has long been the subject of intensive research worldwide. This study examined the morphological and functional evaluation of the regeneration process within the damaged sciatic nerve, a mouse animal model. The effect of impaired expression of the TSC-1 gene on the process of nerve regeneration was evaluated, depending on the mode of damage. The research object consisted of 48, 2-month-old male TSC lines. The test group consisted of animals that underwent damage to the sciatic nerve by crushing, freezing and electrocoagulation, while the control group includes mice whose sciatic nerve was not damaged. Behavioral tests were conducted to evaluate the functional return of the limb, after 3,5,7 and 14 days. The first changes in the regeneration process of the damaged neurite are observed as early as day 3 after the injury, while on day 14 after the injury the functional return of the damaged limb was noted.

Macrophages Modulate Optic Nerve Crush Injury Scar Formation and Retinal Ganglion Cell Function.

Purpose: Optic nerve (ON) injuries can result in vision loss via structural damage and cellular injury responses. Understanding the immune response, particularly the role of macrophages, in the cellular response to ON injury is crucial for developing therapeutic approaches which affect ON injury repair. The present study investigates the role of macrophages in ON injury response, fibrotic scar formation, and retinal ganglion cell (RGC) function. Methods: The study utilizes macrophage Fas-induced apoptosis (MaFIA) mice to selectively deplete hematogenous macrophages and explores the impact macrophages have on ON injury responses. Histological and immunofluorescence analyses were used to evaluate macrophage expression levels and fibrotic scar formation. Pattern electroretinogram (PERG) recordings were used to assess RGC function as result of ON injury. Results: Successful macrophage depletion was induced in MaFIA mice, which led to reduced fibrotic scar formation in the ON post-injury. Despite an increase in activated macrophages in the retina, RGC function was preserved, as demonstrated by normal PERG waveforms for up to 2 months post-injury. The study suggests a neuroprotective role for macrophage depletion in ON damage repair and highlights the complex immune response to ON injury. Conclusions: To our knowledge, this study is the first to use MaFIA mice to demonstrate that targeted depletion of hematogenous macrophages leads to a significant reduction in scar size and the preservation of RGC functionality after ON injury. These findings highlight the key role of hematogenous macrophages in the response to ON injury and opens new avenues for therapeutic interventions in ON injuries. Future research should focus on investigating the distinct roles of macrophage subtypes in ON injury and potential macrophage-associated molecular targets to improve ON regeneration and repair.

Effect of repeated sciatic nerve crush on the conditioning lesion response: Generating an experimental animal model to prolong the denervation period while maintaining peripheral nerve continuity.

Peripheral nerves exhibit long-term residual motor dysfunction following injury. The length of the denervation period before nerve and muscle reconnection is an important factor in motor function recovery. We aimed to investigate whether repeated nerve crush injuries to the same site every 7 days would preserve the conditioning lesion (CL) response and to determine the number of nerve crush injuries required to create an experimental animal model that would prolong the denervation period while maintaining peripheral nerve continuity. Rats were grouped according to the number of sciatic nerve crushes. A significant decrease in the soleus muscle fiber cross-sectional area was observed with increased crushes. After a single crush, macrophage accumulation and macrophage chemotaxis factor CCL2 expression in dorsal root ganglia were markedly increased, which aligned with the gene expression of Ccl2 and its receptor Ccr2. Macrophage numbers, histological CCL2 expression, and Ccl2 and Ccr2 gene expression levels decreased, depending on the number of repeated crushes. Histological analysis and gene expression analysis in the group with four repeated crushes did not differ significantly when compared with uninjured animals. Our findings indicated that repeated nerve crushes at the same site every 7 days sustained innervation loss and caused a loss of the CL response. The experimental model did not require nerve stump suturing and is useful for exploring factors causing prolonged denervation-induced motor dysfunction. SIGNIFICANCE STATEMENT: This study elucidates the effects of repeated nerve crush injury to the same site on innervation and conditioning lesion responses and demonstrates the utility of an experimental animal model that recapitulates the persistent residual motor deficits owing to prolonged denervation without requiring nerve transection and transection suturing.

Augmenting fibronectin levels in injured adult CNS promotes axon regeneration in vivo.

In an attempt to repair injured central nervous system (CNS) nerves/tracts, immune cells are recruited into the injury site, but endogenous response in adult mammals is insufficient for promoting regeneration of severed axons. Here, we found that a portion of retinal ganglion cell (RGC) CNS projection neurons that survive after optic nerve crush (ONC) injury are enriched for and upregulate fibronectin (Fn)-interacting integrins Itga5 and ItgaV, and that Fn promotes long-term survival and long-distance axon regeneration of a portion of axotomized adult RGCs in culture. We then show that, Fn is developmentally downregulated in the axonal tracts of optic nerve and spinal cord, but injury-activated macrophages/microglia upregulate Fn while axon regeneration-promoting zymosan augments their recruitment (and thereby increases Fn levels) in the injured optic nerve. Finally, we found that Fn's RGD motif, established to interact with Itga5 and ItgaV, promotes long-term survival and long-distance axon regeneration of adult RGCs after ONC in vivo, with some axons reaching the optic chiasm when co-treated with Rpl7a gene therapy. Thus, experimentally augmenting Fn levels in the injured CNS is a promising approach for therapeutic neuroprotection and axon regeneration of at least a portion of neurons.

Ficus carica L. (Fig) promotes nerve regeneration in a mouse model of sciatic nerve crush.

Peripheral nerve injuries result in significant loss of motor and sensory function, and the slow rate of nerve regeneration can prolong recovery time. Thus, approaches that promote axonal regeneration are critical to improve the outcomes for patients with peripheral nerve injuries. In this study, we investigated the effects of Ficus carica L. (fig) and Vaccinium macrocarpon Ait. (cranberry), which are rich in phytochemicals with demonstrable and diverse medicinal properties, on nerve regeneration in a mouse model of sciatic nerve crush. Our investigation revealed that fig extract, but not cranberry extract, prevented the decline in muscle weight and nerve conduction velocity induced by nerve crush. The fig extract also mitigated motor function impairment, myelin thinning, and axon diameter reduction, indicating its potential to promote nerve regeneration. Furthermore, the fig extract enhanced macrophage infiltration into the nerve tissue, suggesting that it could ameliorate nerve injury by promoting tissue repair via increased macrophage infiltration. The study provides valuable insights into the potential of the fig extract as a novel agent promoting nerve regeneration. Further investigation into the mechanisms underlying the action of fig extracts is needed to translate these findings into clinical applications for patients with peripheral nerve injuries.

Knockdown of programmed cell death factor 4 restores erectile function by attenuating apoptosis in rats with bilateral cavernous nerve crush injury.

BACKGROUND: Apoptosis is an important pathologic mechanism of erectile dysfunction after radical prostatectomy. Studies have shown that programmed cell death factor 4 is connected to the modulation of apoptosis in many cells. However, the programmed cell death factor 4 function in the cavernous nerve injury erectile dysfunction is unclear. OBJECTIVE: This investigation aimed to explore the programmed cell death factor 4 function in erectile dysfunction in rats with bilateral cavernous nerve crush. MATERIALS AND METHODS: The experiment used 30 male Sprague Dawley rats (18 months old) that were screened for normal erectile function by the apomorphine test. Ten rats were randomized into Sham and bilateral cavernous nerve crush groups to detect changes in programmed cell death factor 4 expression. The remaining 20 rats were distributed at random to four groups: the Sham group treated by sham surgery, the phosphate-buffered saline group, the lentivirus containing negative control short hairpin RNA group, and the lentivirus containing short hairpin RNA targeting programmed cell death factor 4 group underwent bilateral cavernous nerve crush and were afterward administered intracavernous injections of phosphate-buffered saline, lentivirus containing negative control short hairpin RNA, or lentivirus containing short hairpin RNA targeting programmed cell death factor 4. Electrical stimulation of the cavernous nerve was conducted 2 weeks later for penile erectile function assessment. The cavernous tissue was collected for histological analysis and western blotting. RESULTS: The apoptosis level in rat corpus cavernosum was elevated, and programmed cell death factor 4 expression was increased after bilateral cavernous nerve crush. Knockdown of programmed cell death factor 4 significantly improved erectile function in bilateral cavernous nerve crush rats. Furthermore, lentivirus containing short hairpin RNA targeting programmed cell death factor 4 treatment raised smooth muscle content and attenuated cavernous fibrosis and apoptotic levels. Additionally, programmed cell death factor 4 was found to mediate the PI3K/AKT pathway. DISCUSSION AND CONCLUSION: Elevated programmed cell death factor 4 expression may be an important pathogenetic mechanism for erectile dysfunction after bilateral cavernous nerve crush, and the knockdown of programmed cell death factor 4 enhanced erectile function in 18-month-old rats after cavernous nerve damage. The potential mechanism may be the stimulation of the PI3K/AKT pathway to attenuate the cavernous apoptosis level.

CD38 Deficiency Protects Mouse Retinal Ganglion Cells Through Activating the NAD+/Sirt1 Pathway in Ischemia-Reperfusion and Optic Nerve Crush Models.

Purpose: The purpose of this study was to investigate the protective effect of CD38 deletion on retinal ganglion cells (RGCs) in a mouse retinal ischemia/reperfusion (I/R) model and an optic nerve crush (ONC) model, and to elucidate the underlying molecular mechanisms. Methods: Retinal I/R and ONC models were constructed in mice. PCR was used to identify the deletion of CD38 gene in mice, hematoxylin and eosin (H&E) staining was used to evaluate the changes in retinal morphology, and electroretinogram (ERG) was used to evaluate the changes in retinal function. The survival of RGCs and activation of retinal macroglia were evaluated by immunofluorescence staining. The expression of Sirt1, CD38, Ac-p65, Ac-p53, TNF-α, IL-1ß, and Caspase3 proteins in the retina was further evaluated by protein imprinting. Results: In retinal I/R and ONC models, CD38 deficiency reduced the loss of RGCs and activation of macroglia and protected the retinal function. CD38 deficiency increased the concentration of NAD+, reduced the degree of acetylation of NF-κB p65 and p53, and reduced expression of the downstream inflammatory cytokines TNFα, IL-1ß, and apoptotic protein Caspase3 in the retina in the ONC model. Intraperitoneal injection of the Sirt1 inhibitor EX-527 partially counteracted the effects of CD38 deficiency, suggesting that CD38 deficiency acts at least in part through the NAD+/Sirt1 pathway. Conclusions: CD38 plays an important role in the pathogenesis of retinal I/R and ONC injury. CD38 deletion protects RGCs by attenuating inflammatory responses and apoptosis through the NAD+/Sirt1 pathway.

A combination of topical and systemic administration of brimonidine is neuroprotective in the murine optic nerve crush model.

Glaucoma is a multifactorial optic neuropathy that primarily affecting retinal ganglion cells (RGC). Brimonidine is an intraocular pressure-lowering drug with reported neuroprotective properties. This study aimed to compare the neuroprotective effects of topical and intraperitoneal (IP) brimonidine on RGCs from different retinal segments in a murine optic nerve crush (ONC) model. METHODS: forty-one Balb/c mice underwent unilateral ONC and were divided into three study groups: fifteen animals received saline drops twice per day and two additional IP injections of saline; fourteen mice received brimonidine drops twice per day; and 12 mice received brimonidine eye drops twice per day and two additional IP brimonidine injections. Animals were sacrificed seven days post-ONC, and immunohistochemical staining of retinal whole mounts was performed using neuronal NeuN and GFAP staining. Microscopic pictures of the central, middle, and peripheral regions of the retina were taken. The density of the retinal cells was assessed. RESULTS: The total RGC density after ONC and RGC densities in all retinal eccentricities were significantly higher in the brimonidine eye drop and IP combination treatment group than in the saline drop + saline IP, and brimonidine drop treatment groups. CONCLUSIONS: brimonidine eye drops supplemented with IP brimonidine injections improved RGC survival in a preclinical model of ONC.

Cytoprotective Small Compound M109S Attenuated Retinal Ganglion Cell Degeneration Induced by Optic Nerve Crush in Mice.

BAX plays an essential role in retinal ganglion cell (RGC) death induced by optic nerve injury. Recently, we developed M109S, an orally bioactive and cytoprotective small compound (CPSC) that inhibits BAX-mediated cell death. We examined whether M109S can protect RGC from optic nerve crush (ONC)-induced apoptosis. M109S was administered starting 5 h after ONC for 7 days. M109S was orally administered in two groups (5 mg/kg twice a day or 7.5 mg/kg once a day). The retina was stained with anti-BRN3A and cleaved Caspase-3 (active Caspase-3) that are the markers of RGC and apoptotic cells, respectively. ONC decreased the number of BRN3A-positive RGC and increased the number of active Caspase-3-expressing apoptotic cells. In ONC-treated retina, there were cells that were double stained with anti-BRN3A and ant-cleaved Caspase-3, indicating that apoptosis in BRN3A-positive RGCs occurred. M109S inhibited the decrease of BRN3A-positive cells whereas it inhibited the increase of active Caspase-3-positive cells in the retina of ONC-treated mice, suggesting that M109S inhibited apoptosis in RGCs. M109S did not induce detectable histological damage to the lungs or kidneys in mice, suggesting that M109S did not show toxicities in the lung or kidneys when the therapeutic dose was used. The present study suggests that M109S is effective in rescuing damaged RGCs. Since M109S is an orally bioactive small compound, M109S may become the basis for a portable patient-friendly medicine that can be used to prevent blindness by rescuing damaged optic nerve cells from death.

Efectividad del bloqueo de nervios cluneales para tratamiento de dolor lumbar crónico / Effectiveness of cluneal nerve block for the treatment of chronic low back pain

Introducción: El dolor lumbar representa una problemática de salud pública ante la discapacidad que genera, sea motora o sensitiva de etiología multifactorial, en la cual el atrapamiento de los nervios cluneales cumple un papel importante, encontrando como una alternativa al dolor por esta patología el manejo intervencionista. El objetivo principal del estudio fue establecer la efectividad del bloqueo de nervios cluneales en dolor lumbar crónico en pacientes mayores de 18 años de dos hospitales de Bogotá.Métodos: Estudio de tipo observacional, retrospectivo, realizado en pacientes diagnosticados con dolor lumbar crónico y signos y síntomas de atrapamiento de nervios cluneales o clunealgía llevados a bloqueo de nervios cluneales en quienes que se evaluó la intensidad del dolor y duración del efecto analgésico en cuatro momentos.Resultados: Se identificaron 45 pacientes; de estos, 11 no presentaban datos de seguimiento. El 93 % (n = 35) de los pacientes presentaron una EVA (escala visual análoga del dolor) mayor a 7 previo al procedimiento, el 28 % (n = 11) presentaron postbloqueo inmediato mejoría del dolor con una EVA menor a 6, en el primer control el 57 % (n = 22) conservaron la mejoría alcanzada, y el 10 % (n = 4) retornó a su estado basal de dolor. En el segundo, el 10 % (n = 4) de los pacientes no presentaron cambios en la intensidad, y el 78,9 % (n = 30) conservaba mejoría en la intensidad del dolor.Conclusiones: El bloqueo de los nervios cluneales es una alternativa vanguardista de manejo transitorio del dolor lumbar crónico que permitirá seleccionar con mayor objetividad los pacientes candidatos a intervencionismo guiado por fluoroscopia. Se propone la realización de estudios mediante estudios tipo III como los ensayos aleatorizados con grupos donde se administre placebo versus mezclas analgésicas en pacientes con clunealgia.(AU)

Introduction: Low back pain represents a public health problem due to the disability it generates, whether motor or sensory, of multifactorial etiology, in which cluneal nerve entrapment plays an important role, finding an alternative to pain from this pathology. interventional management. The main objective of the study was to establish the efficacy of cluneal nerve block in chronic low back pain in patients older than 18 years from two hospitals in Bogotá.Methods: Observational, retrospective study, carried out in patients diagnosed with chronic low back pain and signs and symptoms of cluneal nerve entrapment or clunealgia leading to cluneal nerve block in whom pain intensity and duration of the analgesic effect were evaluated in four moments.Results: 45 patients were identified; of these, 11 did not present follow-up data. 93 % (n = 35) of the patients presented a VAS (visual analogue pain scale) greater than 7 prior to the procedure, 28 % (n = 11) presented immediate post-block pain improvement with a VAS less than 6, 57 % at the first control (n = 22) maintained the improvement achieved, and 10 % (n = 4) returned to their baseline state of pain. In the second, 10 % (n = 4) of the patients did not show changes in intensity, and 78.9 % (n = 30) maintained improvement in pain intensity.Conclusions: Cluneal nerve blocks are an avant-garde alternative for the temporary management of chronic low back pain that will make it possible to more objectively select patients who are candidates for fluoroscopy-guided intervention. Studies are proposed using type III studies such as randomized trials with groups where placebo is administered versus analgesic mixtures in patients with clunealgia.(AU)

Uncommon causes of nerve compression in the distal forearm / Causas poco frecuentes de compresión nerviosa en el antebrazo distal

Introduction: Nerve compression by anomalous masses located at the wrist and distal forearm is an infrequent condition. They may compress underlying structures in the carpal tunnel region, causing pain and paresthesias, which leads to the wrong diagnosis of carpal tunnel syndrome. Clinical cases: We present three cases of patients with symptomatology and clinical tests compatible with compression of the median nerve in the carpal tunnel but whose physical examination showed a soft mass in the distal region of the forearm which was compressing the median nerve, as demonstrated by ultrasound evaluation. Discussion: The reported cases of accessory muscles or lipomas described in the literature as causes of median nerve compression clinic are mainly described only after the surgical decompression of the carpal tunnel, due to the maintenance of residual symptoms. Conclusion: Careful examination with an ultrasound evaluation prior to surgery may help to identify these cases and help planning surgical treatment.(AU)

Introducción: La compresión del nervio mediano por masas anómalas localizadas en la muñeca y en el antebrazo distal es una condición infrecuente. Las estructuras subyacentes en la región del túnel carpiano pueden ser comprimidas, causando dolor y parestesias, pudiendo llevar al diagnóstico erróneo de síndrome del túnel carpiano. Casos clínicos: Se presentan 3 casos de pacientes con sintomatología y pruebas clínicas compatibles con compresión del nervio mediano en el túnel carpiano. Sin embargo, a la inspección presentaban leve edema en la región proximal del canal, y en la evaluación por ultrasonido se detectó sendas tumoraciones que comprimían el nervio mediano previo a su ingreso en el canal carpiano. Discusión: En la literatura, los casos de músculos accesorios o lipomas como causas de compresión del nervio mediano son las causas más probables de persistencia de los síntomas tras la descompresión quirúrgica del canal carpiano. Conclusión: La exploración clínica detallada junto con la evaluación ultrasonográfica antes de la cirugía pueden ayudar a identificar estos casos y planificar un mejor abordaje quirúrgico.(AU)

Neuralgia del Trigémino / Trigeminal neuralgia

Resumen La neuralgia del trigémino (NT) es una enfermedad cuya prevalencia es alta y corresponde a un porcentaje importante de neuralgias faciales; en donde las personas más afectadas son mayores de 50 años. Su manifestación clínica suele ser de cuadros de dolor facial severo y recurrentes, unilateral; en la distribución de una o más divisiones del nervio trigémino y no se explica con otro diagnóstico. El diagnóstico se basa en el cuadro clínico y usualmente no se encuentra déficit sensorial, sin embargo, si está presente se deben hacer neuroimágenes para descartar otras causas. En primera instancia está el manejo farmacológico. La carbamazepina se ha establecido como efectivo, llegando a producir un alivio del dolor dentro de las 24 horas. Cuando la farmacoterapia falla, se opta por la cirugía que se divide generalmente en dos: técnicas que destruyen la porción sensitiva del nervio; y la descompresión microvascular (DMV), que es la que tiene mejores resultados.

Abstract Trigeminal neuralgia is a disease whose prevalence is high and corresponds to a significant percentage of facial neuralgia; where the most affected people are over 50 years old. The clinical picture is usually of episodes of severe and recurring facial pain, unilateral; in the distribution of one or more divisions of the trigeminal nerve and this is not explained with another diagnosis. Diagnosis is based on the clinic and usually no sensory deficit is found, however, if present, neuroimaging should be done to rule out other causes. In the first instance is the pharmacological management. Carbamazepine has been established as effective, leading to pain relief within 24 hours. When pharmacological therapy fails, surgery is generally divided into two: techniques that destroy the sensitive portion of the nerve and microvascular decompression, which has the best results.

Retinaculotomía endoscópica de doble portal en el síndrome del túnel carpiano / Dual-portal endoscopic release in carpal tunnel syndrome

NiResumen Objetivo: Evaluar los resultados de la retinaculotomía endoscópica para tratar el síndrome del túnel carpiano mediante la técnica de doble portal de Chow, entre enero de 2006 y diciembre de 2015. Materiales y Métodos: Estudio de 179 pacientes (edad promedio 48.2 años [rango 32-68]), con 217 casos de síndrome del túnel carpiano idiopático y un seguimiento promedio de 97.9 meses. Los pacientes eran 145 mujeres (81%) (31 bilaterales) y 34 hombres (19%) (7 bilaterales) y fueron evaluados con la Symptom Severity Scale (SSS) y la Functional Status Scale (FSS) del Boston Carpal Tunnel Questionnaire (BCTQ). Resultados: El puntaje medio de la SSS-BCTQ fue de 3,20 + 0,26 antes de la cirugía, mejoró a 1,30 + 0,12 a los 6 meses y se mantuvo en 1,25 + 0,11 a largo plazo. El puntaje medio de la FSS-BCTQ fue de 2,57 + 0,29 antes de la cirugía, mejoró a 1,28 + 0,18 a los 6 meses y se mantuvo en 1,20 + 0,09 a largo plazo. Hubo 7 casos (3,2%) de neuropraxia posquirúrgica transitoria. No hubo conversiones a técnica abierta. Conclusión: La liberación endoscópica del túnel carpiano con la técnica de Chow es un método quirúrgico eficaz y seguro para tratar el síndrome del túnel carpiano idiopático. Nivel de Evidencia; III

Objective: To evaluate the outcomes of endoscopic release of the transverse carpal ligament (TCL) in carpal tunnel syndrome (CTS) using the Chow dual-portal technique between January 2006 and December 2015. Materials and Methods: Study population consisted of 217 cases of idiopathic CTS, in 179 patients, 145 females (81%) (31 bilateral cases) and 34 males (19%) (7 bilateral cases), with an average age of 48.2 years (range, 32-68) and an average follow-up of 97.9 months. The symptom severity and functional evaluations were performed using the Boston Carpal Tunnel Questionnaire Symptoms Severity Scale (BCTQ-SSS) and the Functional Status Scale (BCTQ-FSS). Results: The average BCTQ-SSS was 3.20±0.26 in the preoperative period, which improved to 1.30±0.12 at the 6-month postoperative follow-up and remained at 1.25±0.11 in the long-term. The average BCTQ-FSS was 2.57±0.29 in the preoperative period, which improved to 1.28±0.12 at the 6-month postoperative follow-up and remained at 1.20±0.09 in the long-term. There were 7 cases (3.2%) of transient postoperative neurapraxia. No patient required to be converted to open technique. Conclusion: The endoscopic carpal tunnel release with Chow technique is an effective and safe surgical method for the treatment of idiopathic CTS. Level of Evidence; III

Changing Concepts for the Diagnosis of Carpal Tunnel Syndrome in Powerlifting Athletes with Disabilities / Mudando os conceitos para o diagnóstico da Síndrome do Túnel do Carpo em atletas do halterofilismo do esporte adaptado

Abstract Objective To examine the prevalence of carpal tunnel syndrome in powerlifting athletes with disabilities. Methods The present study evaluated the presence and intensity of pain (numerical scale), nocturnal paresthesia (self-report), and nerve compression (Tinel and Phalen signs) in wheelchair- and non-wheelchair-bound powerlifting athletes with disabilities. The clinical diagnosis of carpal tunnel syndrome was confirmed by the presence of two or more signs/symptoms. Results In total, 29 powerlifting athletes with disabilities were evaluated. None of the athletes reported the presence of pain or nocturnal paresthesia. The Tinel sign was present in 1 (3.45%) wheelchair-bound athlete. A positive Phalen test was present in 3 (10.35%) athletes (1 wheelchair-bound and 2 non-wheelchair-bound). Concurrent positive Tinel sign and Phalen sign tests were found in 2 (6.89%) athletes (1 wheelchair-bound and 1 non-wheelchair-bound). Conclusion Carpal tunnel syndrome was clinically diagnosed in 2 (6.89%) out of 29 powerlifting athletes with disabilities.

Resumo Objetivo Examinar a prevalência da síndrome do túnel do carpo em atletas do halterofilismo do esporte adaptado. Métodos Este estudo avaliou a presença e a intensidade da dor (escala numérica), a parestesia noturna (autorrelato), e a compressão nervosa (sinais de Tinel e de Phalen) em atletas do halterofilismo do esporte adaptado em cadeira de rodas e sem cadeira de rodas. O diagnóstico clínico da síndrome do túnel do carpo foi confirmado pela presença de dois ou mais sinais/sintomas. Resultados Vinte e nove atletas de halterofilismo de esporte adaptado foram avaliados. Nenhum dos atletas relatou a presença de dor ou parestesia noturna. O sinal de Tinel estava presente em 1 (3,45%) atleta de cadeira de rodas. O teste de Phalen positivo estava presente em 3 (10,35%) atletas (1 em cadeira de rodas e 2 sem cadeira de rodas). Testes positivos de sinais de Tinel e de Phalen foram encontrados concomitantemente em 2 (6,89%) atletas (1 em cadeira de rodas e 1 sem cadeira de rodas). Conclusão A síndrome do túnel do carpo foi diagnosticada clinicamente em 2 (6,89%) dos 29 atletas com deficiência física.

A possible role of endoneurial fibroblast-like cells in the resolution of endoneurial oedema following nerve crush injury / El posible rol de los fibroblastos endoneurales en la resolución del edema endoneural después de una lesión por aplastamiento nervioso

SUMMARY: Endoneurial oedema is a salient feature of all types of neuropathy. Its elimination is crucial during the complications of nerve recovery. The objective was to study a possible role of the endoneurial fibroblasts in the resolution of nerve edema. Forty-two albino male rats aged between 30 and 40 days (weight 200 g to 250 g) were used in this study. The left sural nerves of 36 rats were subjected to crush injury at one to three-week intervals with six animals per interval. The right and left sural nerves of the remaining six rats were used as controls. At the end of the second week after crush injury, the endoneurium showed channel-like spaces that were lined by fibroblast-like cells and collagen bundles that contained degenerated myelin, and were connected to the subperineurial spaces. Flattened fibroblast-like cells were arranged in several layers in the subperineurial, forming barrier-like cellular sheets localizing to the endoneurial oedema in the space. Fibroblast-like cells also wrapped around the regenerating nerve fibres with their branching cytoplasmic processes. During the third week, the flattened fibroblast-like cells formed nearly continuous cellular sheets in the subperineurial spaces. Macrophages were frequently observed between these cellular barrier-like sheets and in the subperineurial. The endoneurial fibroblast-like cells form barrier-like cellular sheets that probably localise the endoneurial oedema in the subperineurial space. It also appear to create endoneurial channel-like spaces containing degenerated myelin and endoneurial oedema, which may be helpful in localizing and resolving such oedema.

RESUMEN: El edema endoneural es una característica destacada de todos los tipos de neuropatía. Su eliminación es importante durante las complicaciones de la recuperación nerviosa. El objetivo fue estudiar un posible papel de los fibroblastos endoneurales en la resolución del edema nervioso. En este estudio se utilizaron 42 ratas macho albinas con edades entre los 30 y 40 días (peso 200 a 250 g). Los nervios surales izquierdos de 36 ratas se sometieron a lesiones por aplastamiento en intervalos de una a tres semanas con seis animales por intervalo. Se usaron los nervios surales derecho e izquierdo de las seis ratas restantes como controles. Al final de la segunda semana después de la lesión por aplastamiento, el endoneuro mostró espacios en forma de canal que estaban revestidos por células similares a fibroblastos y haces de colágeno que contenían mielina degenerada y se conectaron a los espacios subperineurales. Las células aplanadas de fibroblastos se dispusieron en varias capas en el subperineuro, formando láminas celulares de tipo barrera que se localizaban en el espacio del edema endoneural. Las células similares a fibroblastos también envolvían las fibras nerviosas regeneradoras con sus procesos citoplásmicos ramificados. Durante la tercera semana, las células aplanadas de fibroblastos formaron láminas celulares casi continuas en los espacios subperineurales. Los macrófagos se observaron con frecuencia entre estas láminas similares a barreras celulares y en el subperineuro. Las células de tipo fibroblasto endoneural formaban láminas celulares de tipo barrera que probablemente localizan el edema endoneural en el espacio subperineural. También parece que crea espacios en forma de canal endoneural que contienen mielina degenerada y edema endoneural, que pueden ser útiles para localizar y resolver este edema.

A case of cervical rib andneurovascular compression inRoman period

The possibility to study axial anomalies directly on a skeletal individual is not very frequent. One well preserved skeletal individual from an Italian site dating to the late antique period (5th -4th centuries CE) was studied. This individual shows some interesting skeletal changes in the vertebrae and ribs. A supernumerary rib was found. It is a cervical rib connected to the 1st thoracic rib, presumably with a fibrous bundle. The presence of cervical ribs can produce neurovascular compression of the brachial plexus and subclavian vessels. Because of this, it is often a cause of thoracic out-let syndrome (TOS). In our case the presence of a cervical rib articulated with the first thoracic rib through a probable fibrous band could have re-stricted the space where the brachial plexus and subclavian vessels pass through, creating a state of neurovascular compression, similar

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The action of sericin protein on initial nerve repair, associated or not with swimming in wistar rats / Ação da proteína sericina no reparo nervoso inicial, associada ou não à natação, em ratos wistar / Acción de la proteína sericina en la reparación nerviosa inicial, asociada o no a la natación, en ratones wistar

ABSTRACT Objective: To analyze the effects of sericin treatment, associated or not with swimming with load exercise, on initial sciatic nerve repair after compression in Wistar rats. Methods: Forty animals were divided into five groups: control, injury, injury-sericin, injury-swimming and injury-sericin-swimming. During the axonotmesis procedure, the sericin was applied to the injury-sericin and injury-sericin-swimming groups. The injury-swimming and injury-sericin-swimming groups performed the swimming with load exercise for five days, beginning on the third postoperative day (PO), and were evaluated for function, nociception and allodynia. Euthanasia was performed on the 8th PO day and fragments of the nerve were collected and prepared for quantitative and descriptive analysis in relation to the total amount of viable nerve fibers and non-viable nerve fibers, nerve fiber diameter, axon diameter and myelin sheath thickness. Results: There was no significant improvement in the sciatic functional index up to the eighth day. The Von Frey test of the surgical scar and plantar fascia indicated a reduction in pain and allodynia for the injury-swimming and injury-sericin-swimming groups. The morphological analysis presented similar characteristics in the injury-sericin, injury-swimming and injury-sericin-swimming groups, but there was a significant difference in the number of smaller non-viable nerve fibers in the injury-swimming and injury-sericin-swimming groups as compared to the others. Conclusions: Isolated sericin protein presented proinflammatory characteristics. There was improvement of allodynia and a decrease in the pain at the site of the surgical incision, possibly linked to an aquatic effect. There was no acceleration of nerve repair on the eighth day after the injury. Level of Evidence I; High quality randomized clinical trial with or without statistically significant difference, but with narrow confidence intervals.

RESUMO Objetivo: Analisar os efeitos do tratamento da sericina, associada ou não ao exercício de natação com sobrecarga, sobre o reparo inicial do nervo isquiático após compressão em ratos Wistar. Métodos: Foram separados 40 animais em cinco grupos, sendo eles: controle; lesão; lesão-sericina; lesão-natação e lesão-sericina-natação. Durante o procedimento de axonotmese, a sericina foi aplicada sobre a lesão nos grupos lesão-sericina e lesão-sericina-natação. Os grupos lesão-natação e lesão-sericina-natação realizaram o exercício de natação com sobrecarga durante cinco dias, iniciando no terceiro dia pós-operatório (PO), sendo avaliados quanto à função, nocicepção e alodinia. A eutanásia foi realizada no oitavo dia PO, sendo que dois fragmentos do nervo foram coletados e preparados para análise quantitativa e descritiva em relação a quantidade total de fibras nervosas viáveis, não viáveis, diâmetro da fibra nervosa, do axônio e espessura da bainha de mielina. Resultados: No índice funcional isquiático não houve melhora significativa até o oitavo dia. O teste de Von Frey na cicatriz cirúrgica e fáscia plantar indicaram redução do quadro álgico e alodinia para os grupos lesão-natação e lesão-sericina-natação. A análise morfológica apresentou características semelhantes nos grupos lesão-sericina, lesão-natação e lesão-sericina-natação, porém houve diferença significativa das fibras nervosas não viáveis menores nos grupos lesão-natação e lesão-sericina-natação em relação aos demais. Conclusões: A proteína sericina isolada apresentou características pró-inflamatórias. Houve melhora da alodinia e diminuição do quadro álgico no local da incisão cirúrgica relacionadas a possível efeito aquático. Não houve aceleração do reparo nervoso no oitavo dia após a lesão. Nível de Evidência I; Estudo clínico randomizado de alta qualidade com ou sem diferença estatisticamente significante, mas com intervalos de confiança estreitos.

RESUMEN Objetivo: Analizar los efectos del tratamiento de la sericina, asociada o no al ejercicio de natación con sobrecarga, sobre la reparación inicial del nervio isquiático después de compresión, en ratones Wistar. Métodos: Se separaron 40 animales en cinco grupos, siendo: control; lesión; lesión-sericina; lesión-natación y lesión-sericina-natación. Durante el procedimiento de axonotmesis, la sericina fue aplicada sobre la lesión en los grupos lesión-sericina y lesión-sericina-natación. Los grupos lesión-natación y lesión-sericina-natación realizaron el ejercicio de natación con sobrecarga durante cinco días, iniciándose en el tercer día postoperatorio (PO), siendo evaluados cuanto a la función, nocicepción y alodinia. La eutanasia fue realizada en el octavo día PO, siendo que dos fragmentos del nervio fueron recolectados y preparados para análisis cuantitativo y descriptivo, con relación a la cantidad total de fibras nerviosas viables, no viables, diámetro de la fibra nerviosa, del axón y espesor de la vaina de mielina. Resultados: En el índice funcional isquiático no hubo mejoría significativa hasta el octavo día. La prueba de "Von Frey" en la cicatriz quirúrgica y la fascia plantar indicaron reducción del cuadro álgico y alodinia, para los grupos lesión-natación y lesión-sericina-natación. El análisis morfológico presentó características similares en los grupos lesión-sericina, lesión-natación y lesión-sericina-natación, pero hubo diferencia significativa de las fibras nerviosas no viables menores en los grupos lesión-natación y lesión-sericina-natación con relación a los demás. Conclusiones: La proteína sericina aislada presentó características proinflamatorias. Hubo mejora de la alodinia y disminución del cuadro álgico en el lugar de la incisión quirúrgica, relacionadas al posible efecto acuático. No hubo aceleración de la reparación nerviosa en el octavo día después de la lesión. Nivel de Evidencia I; Ensayo clínico aleatorizado de alta calidad con o sin diferencia estadísticamente significativa, pero con intervalos de confianza estrechos.