Immune response in peripheral axons delays disease progression in SOD1G93A mice.

BACKGROUND: Increasing evidence suggests that the immune system has a beneficial role in the progression of amyotrophic lateral sclerosis (ALS) although the mechanism remains unclear. Recently, we demonstrated that motor neurons (MNs) of C57SOD1G93A mice with slow disease progression activate molecules classically involved in the cross-talk with the immune system. This happens a lot less in 129SvSOD1G93A mice which, while expressing the same amount of transgene, had faster disease progression and earlier axonal damage. The present study investigated whether and how the immune response is involved in the preservation of motor axons in the mouse model of familial ALS with a more benign disease course. METHODS: First, the extent of axonal damage, Schwann cell proliferation, and neuromuscular junction (NMJ) denervation were compared between the two ALS mouse models at the disease onset. Then, we compared the expression levels of different immune molecules, the morphology of myelin sheaths, and the presence of blood-derived immune cell infiltrates in the sciatic nerve of the two SOD1G93A mouse strains using immunohistochemical, immunoblot, quantitative reverse transcription PCR, and rotating-polarization Coherent Anti-Stokes Raman Scattering techniques. RESULTS: Muscle denervation, axonal dysregulation, and myelin disruption together with reduced Schwann cell proliferation are prominent in 129SvSOD1G93A compared to C57SOD1G93A mice at the disease onset, and this correlates with a faster disease progression in the first strain. On the contrary, a striking increase of immune molecules such as CCL2, MHCI, and C3 was seen in sciatic nerves of slow progressor C57SOD1G93A mice and this was accompanied by heavy infiltration of CD8+ T lymphocytes and macrophages. These phenomena were not detectable in the peripheral nervous system of fast-progressing mice. CONCLUSIONS: These data show for the first time that damaged MNs in SOD1-related ALS actively recruit immune cells in the peripheral nervous system to delay muscle denervation and prolong the lifespan. On the contrary, the lack of this response has a negative impact on the disease course.

Polysialic acid expression is not necessary for motor neuron target selectivity.

INTRODUCTION: Recovery after peripheral nerve lesions depends on guiding axons back to their targets. Polysialic acid upregulation by regrowing axons has been proposed recently as necessary for this target selectivity. METHODS: We reexamined this proposition using a cross-reinnervation model whereby axons from obturator motor neurons that do not upregulate polysialic acid regenerated into the distal femoral nerve. Our aim was to assess their target selectivity between pathways to muscle and skin. RESULTS: After simple cross-repair, obturator motor neurons showed no pathway preference, but the same repair with a shortened skin pathway resulted in selective targeting of these motor neurons to muscle by a polysialic acid-independent mechanism. CONCLUSION: The intrinsic molecular differences between motor neuron pools can be overcome by manipulation of their access to different peripheral nerve pathways such that obturator motor neurons preferentially project to a terminal nerve branch to muscle despite not upregulating the expression of polysialic acid.

The Spread of Ultrasound-Guided Injectate From the Adductor Canal to the Genicular Branch of the Posterior Obturator Nerve and the Popliteal Plexus: A Cadaveric Study.

BACKGROUND AND OBJECTIVES: The popliteal nerve plexus contributes to afferent knee-pain conduction. It is mainly formed by genicular branches from the posterior obturator and the tibial nerves, innervating the intra-articular and posterior knee region. A subinguinal obturator nerve block alleviates pain after total knee arthroplasty. Reduced hip adductor motor function could be avoided by a posterior obturator nerve block inside the popliteal fossa.The aim of this study was to evaluate the spread of dye after a distal adductor canal (AC) injection to the popliteal fossa and coloring of the popliteal plexus and the genicular branch of the posterior obturator nerve by dissection. We also assessed the spread of dye into the popliteal fossa after a distal femoral triangle injection. METHODS: Ten milliliters of dye was injected into the distal part of the AC in 10 cadaver sides and into the distal part of the femoral triangle in 3 sides. Dissection was used to assess the spread of the injectate and coloring of the popliteal plexus and the genicular branch of the posterior obturator nerve, as well as the saphenous and medial vastus nerves. RESULTS: The popliteal plexus and the genicular branch of the posterior obturator nerve were dyed in all 10 dissections after AC injections. No dye spread into the popliteal fossa after femoral triangle injections. CONCLUSIONS: Injection of 10 mL of dye into the distal part of the AC spreads into the popliteal fossa and colors the popliteal plexus and the genicular branch of the posterior obturator nerve.

Local anesthetic injection deep to the fascia iliaca at the level of the inguinal ligament: the pattern of distribution and effects on the obturator nerve.

STUDY OBJECTIVE: The femoral, lateral femoral cutaneous, and obturator nerves (ONs) can reportedly be blocked using a single-injection deep to the fascia iliaca (FI) at the level of the inguinal ligament. Two commonly used methods (the FI compartment and 3-in-1 blocks) have produced inconsistent results with respect to local anesthetic distribution and effect on the ON. To date, no study of either method has been performed using advanced imaging techniques to document both needle placement and local anesthetic distribution. We report the outcome of a series of 3-in-1 and FI blocks performed using ultrasound to guide needle position and magnetic resonance imaging (MRI) to define local anesthetic distribution. DESIGN: Patients were prospectively studied, and images were interpreted using a randomized and blinded protocol. SETTING: The study was performed in the perioperative area of an academic orthopedic specialty hospital. PATIENTS: Ten patients (ASA 1-2) having anterior cruciate ligament reconstruction received either 3-in-1 or FI compartment blocks for postoperative analgesia using the surface landmarks described for these techniques. INTERVENTIONS: Ultrasound was used to position the injecting needle immediately deep to the FI. Local anesthetic distribution was studied using MRI. MEASUREMENTS: Patients were examined for motor and/or sensory function of the femoral, obturator, and lateral femoral cutaneous nerves. Magnetic resonance imaging was used to document the limits of injectate distribution. MAIN RESULTS: Magnetic resonance imaging showed distribution of injectate over the surface of the iliacus and psoas muscles to the level of the retroperitoneum. No patient showed medial extension of injectate to the ON. At the level of the inguinal ligament, injectate extended laterally toward the anterior superior iliac spine and medially to the femoral vein. All patients had significant weakness with extension of the knee and sensory loss over the anterior, lateral, and medial thigh. No patient demonstrated decreased hip adductor strength. CONCLUSIONS: Ultrasound and MRI show consistent superior extension of local anesthetic to the level of the retroperitoneum for both techniques. There was reliable clinical effect on the femoral and lateral femoral cutaneous nerves. However, none of the injections produced evidence of ON block either at the level of the retroperitoneum or the inguinal ligament.

Femoral nerve "sheath" for inguinal paravascular lumbar plexus block is not found in human cadavers.

STUDY OBJECTIVE: To determine if a femoral nerve sheath capable of conveying local anesthetic to the lumbar plexus and the obturator nerve exists in human cadavers. DESIGN: Injection of methylene blue dye into the femoral nerves of human cadavers followed by dissection and observation of dye distribution. SETTING: University medical center pathology department autopsy room. PATIENTS: Six fresh adult cadavers about to undergo postmortem examination. INTERVENTIONS: Both femoral nerves of six fresh cadavers were injected with either 20 ml or 40 ml of dye. The abdomen was opened and distribution of the dye was observed. MEASUREMENTS AND MAIN RESULTS: In all of the cadavers studied there was no evidence of a femoral nerve sheath capable of conveying methylene blue dye to the lumbar plexus. Both 20 ml and 40 ml of dye injected into the femoral nerve failed to reach the lumbar plexus or the obturator nerve. When 40 ml of dye was injected it always stained the femoral nerves, it usually stained the lateral femoral cutaneous nerves, but it never stained the obturator nerves. CONCLUSIONS: A femoral nerve sheath capable of conveying a solution to the cadaver lumbar plexus does not exist in human cadavers. Dye injected into the cadaver femoral nerve does not reach either the lumbar plexus or the obturator nerve. When 40 ml of methylene blue dye is injected into the cadaver femoral nerve, some dye usually diffuses under the iliacus muscle fascia to the lateral femoral cutaneous nerve. This study indicates that in patients the "3-in-1 block" always blocks the femoral nerve, it usually blocks the lateral femoral cutaneous nerve, but it probably does not block the lumbar plexus or the obturator nerve.

Bloqueo intraarticular y de ramas sensoriales de los nervios obturador y femoral en cuadro de osteonecrosis y artrosis de cabeza femoral / Joint and sensory branch block of the obturator and femoral nerves in a case of femoral head osteonecrosis and arthritis

La inervación sensitiva de la articulación de la cadera es compleja. El bloqueo intraarticular y de las ramas sensitivas de los nervios obturador y femoral es eficaz para tratar el dolor producido por diversas enfermedades de cadera, y pudiera ser una opción a considerar en determinadas circunstancias. Estas circunstancias pueden ser alto riesgo quirúrgico-anestésico por el estado basal del paciente o la existencia de sobrepeso importante, en otras ocasiones el médico traumatólogo considera que es mejor retrasar la artroplastia, al menos durante algún tiempo (AU)

The sensory innervation of the hip joint is complex. The joint and sensory branch block of the obturator and femoral nerves is effective for treating the pain caused due to different hip diseases. This could be an option to be considered in certain circumstances such as, being a surgical-anaesthetic high risk, or if there is significant overweight, It could also be useful on other occasions if the traumatoligist considers that it is better to delay hip replacement for a limited period (AU)