Modeling optical design parameters for fine stimulation in sciatic nerve of optogenetic mice.

Optogenetics presents an alternative method for interfacing with the nervous system over the gold-standard of electrical stimulation. While electrical stimulation requires electrodes to be surgically embedded in tissue for in vivo studies, optical stimulation offers a less-invasive approach that may yield more specific, localized stimulation. The advent of optogenetic laboratory animals-whose motor neurons can be activated when illuminated with blue light-enables research into refining optical stimulation of the mammalian nervous system where subsets of nerve fibers within a nerve may be stimulated without embedding any device directly into the nerve itself. However, optical stimulation has a major drawback in that light is readily scattered and absorbed in tissue thereby limiting the depth with which a single emission source can penetrate. We hypothesize that the use of multiple, focused light emissions deployed around the circumference of a nerve can overcome these light-scattering limitations. To understand the physical parameters necessary to produce pinpointed light stimulation within a single nerve, we employed a simplified Monte Carlo simulation to estimate the size of nerves where this technique may be successful, as well as the necessary optical lens design for emitters to be used during future in vivo studies. By modeling multiple focused beams, we find that only fascicles within a nerve diameter less than 1 mm are fully accessible to focused optical stimulation; a minimum of 4 light sources is required to generate a photon intensity at a point in a nerve over the initial contact along its surface. To elicit the same effect in larger nerves, focusing lenses would require a numerical aperture [Formula: see text]. These simulations inform on the design of instrumentation capable of stimulating disparate motor neurons in mouse sciatic nerve to control hindlimb movement.

Nerve conduction assessment and magnetic resonance imaging for the diagnosis of localized hypertrophic neuropathy of the sciatic nerve and the lumbo-sacral plexus.

Localized hypertrophic neuropathy (LHN) are slowly growing nerve lesions causing progressive nerve deficit and weakness. We present the case of a 32-year old woman with long history of motor and sensory deficit complains along the sciatic nerve territory. The muscles involved were featured by delay in F waves at nerve conduction assessment. Magnetic resonance imaging (MRI) showed specific patterns, low intense on T1 and abnormally hyper intense on short tau inversion recovery (STIR) and T2, with no obvious enhancement, features compatible with either LHN or intraneural perineurioma (IP) of the sciatic nerve and/or the lumbosacral plexus. Focal thickening and hypertrophy of the sciatic nerve with preserved fascicular configuration and progressive enlargement of the right lumbosacral plexus could be noted. A nerve conduction assessment followed by an MRI eventually allowed to diagnose LHN, without performing a nerve biopsy. Although similar, LHN and IP are two distinct lesions which should be diagnosed and differentiated as soon as possible, to avoid potential complications due to delayed diagnosis and/or misdiagnosis.

Quantitative assessment of sciatic nerve changes in Charcot-Marie-Tooth type 1A patients using magnetic resonance neurography.

BACKGROUND AND PURPOSE: Nerve tissue alterations have rarely been quantified in Charcot-Marie-Tooth type 1A (CMT1A) patients. The aim of the present study was to quantitatively assess the magnetic resonance imaging (MRI) anomalies of the sciatic and tibial nerves in CMT1A disease using quantitative neurography MRI. It was also intended to seek for correlations with clinical variables. METHODS: Quantitative neurography MRI was used in order to assess differences in nerve volume, proton density and magnetization transfer ratio in the lower limbs of CMT1A patients and healthy controls. Disease severity was evaluated using the Charcot-Marie-Tooth Neuropathy Score version 2, Charcot-Marie-Tooth examination scores and Overall Neuropathy Limitations Scale scores. Electrophysiological measurements were performed in order to assess the compound motor action potential and the Motor Unit Number Index. Clinical impairment was evaluated using muscle strength measurements and Charcot-Marie-Tooth examination scores. RESULTS: A total of 32 CMT1A patients were enrolled and compared to 13 healthy subjects. The 3D nerve volume, magnetization transfer ratio and proton density were significantly different in CMT1A patients for the whole sciatic and tibial nerve volume. The sciatic nerve volume was significantly correlated with the whole set of clinical scores whereas no correlation was found between the tibial nerve volume and the clinical scores. CONCLUSION: Nerve injury could be quantified in vivo using quantitative neurography MRI and the corresponding biomarkers were correlated with clinical disability in CMT1A patients. The sensitivity of the selected metrics will have to be assessed through repeated measurements over time during longitudinal studies to evaluate structural nerve changes under treatment.

Ultrasonographic Assessment of the Distance of Sciatic Nerve Bifurcation from the Popliteal Crease and its Depth from Skin in Volunteers.

Background Sciatic nerve block used for various surgeries below knee and for maintenance of analgesia demonstrates wide variability regarding its bifurcation into tibial and common peroneal nerves, frequently accounting for incomplete nerve blocks. Objective To determine the variation of sciatic nerve bifurcation among Nepalese volunteers. Method This cross sectional study was conducted in the Department of Anesthesiology of Kathmandu Medical College Teaching Hospital from March to May 2019, where 110 healthy volunteers underwent ultrasonography of sciatic nerve starting from popliteal fossa to its bifurcation. The distance between the bifurcation of sciatic nerve from popliteal crease and depth of the nerve at that point from the skin were measured. Result The mean distance at which sciatic nerve bifurcated from the popliteal crease was 5.42 ± 1.37 cm. Most commonly, the sciatic nerve bifurcated at a distance of 5-7 cm from the popliteal crease in 110 limbs (50.45%). However, in 80 limbs (36.69%), the bifurcation was found at less than 5 cm from the popliteal crease. The depth of the nerve from the skin at the point of bifurcation was 1.72 ± 0.54 cm, with results showing it was deeper in females compared to males (p value < 0.001). Conclusion This study showed that though the distance of sciatic nerve bifurcation from the popliteal crease in our study group was coherent with the published literature of 5-12 cm; many volunteers also had this bifurcation at distances less than 5 cm. Females showed nerves to be deeper at the point of bifurcation than males.

Low frequency oscillating gradient spin-echo sequences improve sensitivity to axon diameter: An experimental study in viable nerve tissue.

Mapping axon diameters within the central and peripheral nervous system could play an important role in our understanding of nerve pathways, and help diagnose and monitor an array of neurological disorders. Numerous diffusion MRI methods have been proposed for imaging axon diameters, most of which use conventional single diffusion encoding (SDE) spin echo sequences. However, a growing number of studies show that oscillating gradient spin echo (OGSE) sequences can provide additional advantages over conventional SDE sequences. Recent theoretical results suggest that this is especially the case in realistic scenarios, such as when fibres have unknown or dispersed orientation. In the present study, we adopt the ActiveAx approach to experimentally investigate the extent of these advantages by comparing the performances of SDE and trapezoidal OGSE in viable nerve tissue. We optimise SDE and OGSE ActiveAx protocols for a rat peripheral nerve tissue and test their performance using Monte Carlo simulations and a 800 mT/m gradient strength pre-clinical imaging experiment. The imaging experiment uses excised sciatic nerve from a rat's leg placed in a MRI compatible viable isolated tissue (VIT) maintenance chamber, which keeps the tissue in a viable physiological state that preserves the structural complexity of the nerve and enables lengthy scan times. We compare model estimates to histology, which we perform on the nerve post scanning. Optimisation produces a three-shell SDE and OGSE ActiveAx protocol, with the OGSE protocol consisting of one SDE sequence and two low-frequency oscillating gradient waveform sequences. Both simulation and imaging results show that the OGSE ActiveAx estimates of the axon diameter index have a higher accuracy and a higher precision compared to those from SDE. Histology estimates of the axon diameter index in our nerve tissue samples are 4-5.8 µm and these are excellently matched with the OGSE estimates 4.2-6.5 µm, while SDE overestimates at 5.2-8 µm for the same sample. We found OGSE estimates to be more precise with on average a 0.5 µm standard deviation compared to the SDE estimates which have a 2 µm standard deviation. When testing the robustness of the estimates when the number of the diffusion gradient directions reduces, we found that both OGSE and SDE estimates are affected, however OGSE is more robust to these changes than the SDE. Overall, these results suggest, quantitatively and in in vivo conditions, that low-frequency OGSE sequences may provide improved accuracy of axon diameter mapping compared to standard SDE sequences.

Is diffusion tensor imaging useful in the assessment of the sciatic nerve and its pathologies? Our clinical experience.

OBJECTIVE: To evaluate the usefulness of diffusion tensor imaging (DTI) in the clinical setting as a complementary tool to conventional MRI in the study and assessment of the sciatic nerve and its pathologies. METHODS: 17 patients diagnosed with different types of sciatic neuropathy and 10 healthy controls underwent a conventional MRI and a DTI study in a 3-T MR scanner (Achieva(®) 3-T X-Series; Philips Healthcare, Netherlands). RESULTS: In the control group, we were able to track and visualize the common sciatic nerve and its main branches from hip to foot. In the patient group, the affected sciatic nerves presented statistically significant lower fractional anisotropy values and higher apparent diffusion coefficient values when compared with controls, suggesting nerve damage. In all cases, DTI offered complementary information for diagnosis and/or confirmation of the suspected pathology. When compared with conventional MRI, DTI showed higher sensitivity for nerve damage detection. CONCLUSION: DTI offers a significant improvement and an important complement to visualize the sciatic nerve and its main branches. In patients with sciatic nerve pathology DTI allows to a better detection and characterization of the nerve damage. ADVANCES IN KNOWLEDGE: DTI enables in vivo dissection of the sciatic nerve white matter fibres; its use offers a significant improvement and complement to conventional MRI.

Non-invasive assessment of sciatic nerve stiffness during human ankle motion using ultrasound shear wave elastography.

Peripheral nerves are exposed to mechanical stress during movement. However the in vivo mechanical properties of nerves remain largely unexplored. The primary aim of this study was to characterize the effect of passive dorsiflexion on sciatic nerve shear wave velocity (an index of stiffness) when the knee was in 90° flexion (knee 90°) or extended (knee 180°). The secondary aim was to determine the effect of five repeated dorsiflexions on the nerve shear wave velocity. Nine healthy participants were tested. The repeatability of sciatic nerve shear wave velocity was good for both knee 90° and knee 180° (ICCs ≥ 0.92, CVs ≤ 8.1%). The shear wave velocity of the sciatic nerve significantly increased (p<0.0001) during dorsiflexion when the knee was extended (knee 180°), but no changes were observed when the knee was flexed (90°). The shear wave velocity-angle relationship displayed a hysteresis for knee 180°. Although there was a tendency for the nerve shear wave velocity to decrease throughout the repetition of the five ankle dorsiflexions, the level of significance was not reached (p=0.055). These results demonstrate that the sciatic nerve stiffness can be non-invasively assessed during passive movements. In addition, the results highlight the importance of considering both the knee and the ankle position for clinical and biomechanical assessment of the sciatic nerve. This non-invasive technique offers new perspectives to provide new insights into nerve mechanics in both healthy and clinical populations (e.g., specific peripheral neuropathies).

Intraneural or extraneural: diagnostic accuracy of ultrasound assessment for localizing low-volume injection.

BACKGROUND AND OBJECTIVES: When one is performing ultrasound-guided peripheral nerve blocks, it is common to inject a small amount of fluid to confirm correct placement of the needle tip. If an intraneural needle tip position is detected, the needle can then be repositioned to prevent injection of a large amount of local anesthetic into the nerve. However, it is unknown if anesthesiologists can accurately discriminate intraneural and extraneural injection of small volumes. Therefore, this study was conducted to determine the diagnostic accuracy of ultrasound assessment using a criterion standard and to compare experts and novices in ultrasound-guided regional anesthesia. METHODS: A total of 32 ultrasound-guided infragluteal sciatic nerve blocks were performed on 21 cadaver legs. The injections were targeted to be intraneural (n = 18) or extraneural (n = 14), and 0.5 mL of methylene blue 1% was injected. Cryosections of the nerve and surrounding tissue were assessed by a blinded investigator as "extraneural" or "intraneural." Ultrasound video clips of the injections were reviewed by 10 blinded observers (5 experts, 5 novices) independently who scored each injection as either "intraneural," "extraneural," or "undetermined." RESULTS: The mean sensitivity of experts and novices was measured to be 0.84 (0.80-0.88) and 0.65 (0.60-0.71), respectively (P = 0.006), whereas mean specificity was 0.97 (0.94-0.98) and 0.98 (0.96-0.99) (P = 0.53). CONCLUSIONS: Discrimination of intraneural or extraneural needle tip position based on an injection of 0.5mL is possible, but even experts missed 1 of 6 intraneural injections. In novices, the sensitivity of assessment was significantly lower, highlighting the need for focused education.

Assessment of postoperative analgesia after application of ultrasound-guided regional anesthesia for surgery in a swine femoral fracture model.

Management of pain in research swine used for studies involving painful procedures is a considerable challenge. Here we assessed whether a regional anesthesia method is effective for pain control of hindlimb injuries in pigs used for research in bone fracture healing. For this randomized controlled study, we administered regional anesthesia before an experimental femoral injury was produced. Using ultrasound guidance, we placed sterile infusion catheters near the sciatic and femoral nerves and administered local anesthetic (bupivacaine) for the first 24 h after surgery. We evaluated various behavioral and physiologic parameters to test the hypothesis that this regional anesthesia would provide superior analgesia compared with systemic analgesia alone. We also collected blood samples to evaluate serum levels of cortisol and fentanyl postoperatively. At the end of the study period, we collected sciatic and femoral nerves and surrounding soft tissues for histopathologic evaluation. Treatment pigs had lower subjective pain scores than did control animals. Control pigs had a longer time to first feed consumption and required additional analgesia earlier in the postoperative period than did treatment pigs. Ultrasound-guided regional anesthesia is a viable and effective adjunct to systemic analgesics for providing pain control in swine with experimental femoral fractures.

Is ultrasound guidance mandatory when performing paediatric regional anaesthesia?

PURPOSE OF REVIEW: Since Kapral in 1994 first described the use of real-time ultrasound-guided regional anaesthesia, this novel technique has gained widespread recognition in adult practice and has been shown to be associated with clinically relevant advantages. The aim of this manuscript is to review the currently published paediatric data associated with the use of ultrasound-guided regional anaesthesia. RECENT FINDINGS: Compared with alternative techniques ultrasound guidance is associated with an increased success rate, reduced onset time, moderately prolonged duration, reduced need for local anaesthetics and lower costs, and may also be considered to reduce the risk for complications. SUMMARY: Based on current data the use of ultrasound guidance is strongly recommended when performing peripheral nerve blocks in infants and children. Concerning ultrasound assistance in relation to paediatric neuroaxial blocks there is currently not enough supporting evidence to issue a general recommendation regarding its routine use.

[Neurolymphomatosis: diagnosis of extension and assessment of response to treatment with PET-CT]. / Neurolinfomatosis: diagnóstico de extensión y valoración de la respuesta al tratamiento mediante PET-TAC.

Neurolymphomatosis is a rare neurological manifestation of non-Hodgkin's lymphoma (NHL) and it may be its first and sole manifestation. Diagnosis is often difficult and nerve biopsy is generally required. However, this it is not always possible to perform or is not conclusive. We present the case of a 66-year-old woman diagnosed with giant B-cell NHL. After 6 cycles of chemotherapy, imaging and molecular biology techniques showed complete remission. At four months after treatment, the patient complained of low back pain of radicular distribution. CT and MRI imaging showed signs of lymphoproliferative activity of L5 and also lesions to thoracic nerve roots. A PET-CT was requested in order to complete the diagnosis and plan the treatment. Imaging confirmed the presence of tumor recurrence with neurolymphomatosis and also indicated lesions on the chest and abdominal level. Thus, it was decided to start a new line of chemotherapy, without performing the histological study through biopsy. This case illustrates the important role played by PET-CT imaging in neurolymphomatosis diagnosis. This technique can help the patient avoid more aggressive procedures, such as a biopsy, and can also be useful in the follow-up and assessment of the treatment response to NHL-diagnosed patients.

Ultrasonographic assessment of the canine sciatic nerve.

To describe the ultrasonographic technique for investigation of the canine sciatic nerve, four canine cadaver pelvic limbs, two live healthy dogs, and five canine patients with suspected peripheral sciatic nerve lesions were examined with a high-resolution linear ultrasound transducer. The caudal part of the lumbosacral trunk and the origin of the sciatic nerve were visualized through the greater ischiatic foramen. The two components of the sciatic nerve, common peroneal and tibial nerves, were distinguished along the entire length of the nerve, until they branched at the level of the distal femur. In healthy live dogs they appeared as two adjacent hypoechoic tubular structures with internal echotexture of discontinuous hyperechoic bands, surrounded by a thin rim of highly echogenic tissue. The common peroneal component had a smaller diameter and was on the cranial aspect of the tibial component. An ultrasonographic lesion compatible with a peripheral nerve sheath tumor was found in one dog. Improved understanding of the ultrasonographic anatomy of the sciatic nerve supports clinical use of this modality.

Increased sciatic nerve blood flow in diabetic rats: assessment by "molecular" vs. particulate microspheres.

Sciatic nerve blood flow in diabetic rats in typically increased or unchanged when assessed by the reference sample microsphere method in our laboratory. In contrast, blood flow is generally reported to be decreased approximately 50% when assessed with laser Doppler flowmetry or hydrogen clearance polarography. To address concerns that increased blood flow observed with microspheres might be anomalous because of their particulate nature and/or because insufficient numbers of microspheres are captured in the nerve, a plasma-soluble "molecular microsphere" ([3H]desmethylimipramine, mol wt = 266) and 11.3-micron 153Gd-labeled microspheres were injected sequentially to assess blood flow in rats with streptozotocin diabetes of 2-4 wk duration. Nerve blood flows in diabetic rats were increased 1.5- to 2-fold (vs. control rats) with both tracers; these increases were prevented by tolrestat, an inhibitor of aldose reductase. These observations indicate that blood flow in sciatic nerve (like that in retina and kidney) is increased early after the onset of diabetes and is 1) demonstrable with a plasma-soluble tracer as well as with particulate microspheres and 2) linked to increased metabolism of glucose via the sorbitol pathway.