Investigating the effects of dopamine on short- and long-latency afferent inhibition.

Short- and long-latency afferent inhibition (SAI and LAI respectively) are phenomenon whereby the motor evoked potential induced by transcranial magnetic stimulation (TMS) is inhibited by a sensory afferent volley consequent to nerve stimulation. It remains unclear whether dopamine participates in the genesis or modulation of SAI and LAI. The present study aimed to determine if SAI and LAI are modulated by levodopa (l-DOPA). In this placebo-controlled, double-anonymized study Apo-Levocarb (100 mg l-DOPA in combination with 25 mg carbidopa) and a placebo were administered to 32 adult males (mean age 24 ± 3 years) in two separate sessions. SAI and LAI were evoked by stimulating the median nerve and delivering single-pulse TMS over the motor hotspot corresponding to the first dorsal interosseous muscle of the right hand. SAI and LAI were quantified before and 1 h following ingestion of drug or placebo corresponding to the peak plasma concentration of Apo-Levocarb. The results indicate that Apo-Levocarb increases SAI and does not significantly alter LAI. These findings support literature demonstrating increased SAI following exogenous dopamine administration in neurodegenerative disorders. KEY POINTS: Short- and long-latency afferent inhibition (SAI and LAI respectively) are measures of corticospinal excitability evoked using transcranial magnetic stimulation. SAI and LAI are reduced in conditions such as Parkinson's disease which suggests dopamine may be involved in the mechanism of afferent inhibition. 125 mg of Apo-Levocarb (100 mg dopamine) increases SAI but not LAI. This study increases our understanding of the pharmacological mechanism of SAI and LAI.

Prognostic factors in carpal tunnel syndrome treated with 5% dextrose perineural injection: A retrospective study.

Background: Perineural injection therapy with 5% dextrose water (D5W) is a potential and innovative treatment with long-term efficacy for carpal tunnel syndrome (CTS). However, the prognostic factors of this management are lacking; hence, the aim of this retrospective study was to identify the prognostic factors of D5W perineural injection therapy for mild-to-moderate CTS. Methods: A total of 52 patients (52 wrists) diagnosed with mild-to-moderate CTS and treated with a single ultrasound-guided 5cc D5W perineural injection were retrospectively reviewed. Patient-reported injection outcomes (visual analog scale, VAS) at 6 months post-injection were categorized into two groups; (1) Good outcome, when symptom relief ≥50% compared to pre-injection and (2) Poor outcome, when symptom relief < 50% compared to pre-injection. Significant variables between groups were entered into a binary logistic regression with forward stepwise regression to determine the prognostic factors for these outcomes. Results: The treatment outcome was significantly related to body height and sensory nerve conduction velocity (SNCV) (159.1 ± 1.0 vs. 155.0 ± 1.8, p=0.04; 33.6 ± 0.8 vs. 28.3 ± 1.2, p=0.001, good vs. poor outcomes). However, only SNCV remained significantly correlated with the outcomes after conducting stepwise logistic regression (ORs: 1.201; 95% CI 1.05-1.38; p=0.01). Conclusions: SNCV was found to be a significant prognostic factor of treatment outcome for patients with mild-to-moderate CTS 6 months after a D5W perineural injection.

Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray.

Adequate pain management remains an unmet medical need. We previously revealed an opioid-independent analgesic mechanism mediated by orexin 1 receptor (OX1R)-initiated 2-arachidonoylglycerol (2-AG) signaling in the ventrolateral periaqueductal gray (vlPAG). Here, we found that low-frequency median nerve stimulation (MNS) through acupuncture needles at the PC6 (Neiguan) acupoint (MNS-PC6) induced an antinociceptive effect that engaged this mechanism. In mice, MNS-PC6 reduced acute thermal nociceptive responses and neuropathy-induced mechanical allodynia, increased the number of c-Fos-immunoreactive hypothalamic orexin neurons, and led to higher orexin A and lower GABA levels in the vlPAG. Such responses were not seen in mice with PC6 needle insertion only or electrical stimulation of the lateral deltoid, a nonmedian nerve-innervated location. Directly stimulating the surgically exposed median nerve also increased vlPAG orexin A levels. MNS-PC6-induced antinociception (MNS-PC6-IA) was prevented by proximal block of the median nerve with lidocaine as well as by systemic or intravlPAG injection of an antagonist of OX1Rs or cannabinoid 1 receptors (CB1Rs) but not by opioid receptor antagonists. Systemic blockade of OX1Rs or CB1Rs also restored vlPAG GABA levels after MNS-PC6. A cannabinoid (2-AG)-dependent mechanism was also implicated by the observations that MNS-PC6-IA was prevented by intravlPAG inhibition of 2-AG synthesis and was attenuated in Cnr1-/- mice. These findings suggest that PC6-targeting low-frequency MNS activates hypothalamic orexin neurons, releasing orexins to induce analgesia through a CB1R-dependent cascade mediated by OX1R-initiated 2-AG retrograde disinhibition in the vlPAG. The opioid-independent characteristic of MNS-PC6-induced analgesia may provide a strategy for pain management in opioid-tolerant patients.

Carpal tunnel syndrome and associated nail changes: Review and examples from the author's practice.

Carpal tunnel syndrome (CTS) is commonly seen by general practitioners and often presents with neurologic symptoms of nocturnal pain and paresthesia along the median nerve distribution. Approximately 20% of patients also present with cutaneous findings (ulcerations, blistering, sclerodactyly, nail dystrophy) characterizing a severe form called necrotic CTS. Necrotic CTS can also be associated with bone changes (acro-osteolysis). In the author's practice, combined nail and skin findings are not an uncommon presentation of CTS, although this form remains overlooked and underreported in the dermatological textbooks and studies. This manuscript aims to review the literature on CTS cases, with a specific focus on using associated nail findings as diagnostic clues. The literature review along with a few additional recent cases from the author's practice demonstrate that CTS is frequently accompanied by a variety of nail changes including koilonychia, longitudinal fissuring, Beau's lines, onychomadesis, melanonychia, nail thickening, hyperkeratosis, and ischemic ulcerations with paronychia. Furthermore, when these changes are limited to the second and third fingernails, they should prompt the diagnosis of CTS. Once suspected, diagnostic evaluation is not difficult and surgical management can resolve cutaneous findings and prevent irreversible changes such as acro-osteolysis.

Comparison of Corticosteroid Injection Dosages in Mild to Moderate Idiopathic Carpal Tunnel Syndrome: A Randomized Controlled Trial.

OBJECTIVES: To evaluate whether the therapeutic effect of ultrasound-guided injections with 10 mg or 40 mg triamcinolone acetonide (TA) was dose-dependent in patients with idiopathic mild to moderate carpal tunnel syndrome (CTS). DESIGN: Prospective, double-blind, randomized controlled study with 12 weeks of follow-up. SETTING: Rehabilitation outpatient clinic of a single medical center. PARTICIPANTS: Patients with CTS (N=56). INTERVENTION: Participants were randomly assigned to 2 treatment groups for injection: (A) 40 mg TA+2% lidocaine hydrochloride or (B) 10 mg TA+2% lidocaine hydrochloride. MAIN OUTCOME MEASURES: Participants were evaluated using visual analog scale (VAS) and Boston Carpal Tunnel Questionnaire (BCTQ, including Symptom Severity Scale [SSS] and Functional Status Scale [FSS]) at baseline and 6 and 12 weeks after injection). Nerve conduction studies, including parameters of distal motor latency, amplitude of compound motor action potential, amplitude of sensory nerve action potential and sensory nerve conduction velocity of median nerve, and the patient's subjective impression of improvement, were recorded before injection and 6 and 12 weeks after injection. RESULTS: No significant differences were observed in baseline demographic characteristics and clinical evaluations. The parameters in group A and B at baseline, 6 weeks, and 12 weeks were (1) SSS: 2.17±0.14, 1.19±0.04, and 1.34±0.09 and 1.87±0.11, 1.21±0.07, and 1.26±0.04; (2) FSS: 1.63±0.07, 1.27±0.06, and 1.33±0.08 and 1.50±0.10, 1.18±0.05, and 1.26±0.05; (3) VAS: 6.4±0.3, 2.2±0.3, and 3.0±0.1 and 6.7±0.3, 2.0±0.3, and 3.1±0.3, respectively, and significantly decreased after 6 and 12 weeks in both treatment groups (P<.05). All parameters of nerve conduction studies improved in both groups after 12 weeks (P<.05). VAS, BCTQ, and nerve conduction studies did not show significant intergroup differences after 6 and 12 weeks. CONCLUSION: In patients with idiopathic mild to moderate CTS, ultrasound-guided injection with 10 and 40 mg TA yield similar improvements in BCTQ, VAS, and nerve conduction studies at the 12-week follow-up.

A randomized controlled trial: comparing extracorporeal shock wave therapy versus local corticosteroid injection for the treatment of carpal tunnel syndrome.

PURPOSE: Extracorporeal shock wave therapy (ESWT) has been reported as a new therapy for carpal tunnel syndrome (CTS). However, few studies have compared ESWT with the local corticosteroid injection (LCI). METHODS: In this study, a randomized controlled trial comparing 30 patients with ESWT and 25 patients treated with LCI was conducted. The clinical outcomes were obtained with tests including the visual analog scale (VAS) for pain and paresthesia, the Boston Carpal Tunnel Questionnaire (BQ), and a nerve conduction study, before the study started and at three, nine, and 12 weeks after the start of the treatment. RESULTS: Significantly greater improvement in the VAS and BQ scores was noted for the ESWT group than for the LCI group (P < 0.05). For the nerve conduction study, there was a significant improvement in the median nerve sensory nerve action potential distal latency at the nine and 12-week follow-ups for the ESWT group. CONCLUSIONS: ESWT is a useful noninvasive short-term treatment for mild to moderate carpal tunnel syndrome and elicits a better recovery than LCI does, but more research is needed to test the clinical outcomes of ESWT.

Randomized double-blinded clinical trial of 5% dextrose versus triamcinolone injection for carpal tunnel syndrome patients.

OBJECTIVE: Perineural injection with 5% dextrose (D5W) is a novel strategy in the treatment of carpal tunnel syndrome (CTS). In contrast, perineural injection with corticosteroid has been used for decades for treating CTS, but possible neurotoxicity has been a major concern. No studies investigating the comparative effects have been published so far. The authors performed a prospective, randomized, double-blinded, head-to-head comparative trial to compare these two approaches for patients having mild-to-moderate CTS. METHODS: Fifty-four participants with mild-to-moderate CTS were randomly divided into dextrose and steroid groups. The patients were administered 1 session of perineural injection with 5ml D5W (dextrose group) or 3ml triamcinolone acetonide mixed with 2ml normal saline (steroid group), under ultrasound guidance. A visual analog scale was assigned to assess the primary outcome. The secondary outcomes were assessed using the Boston Carpal Tunnel Syndrome Questionnaire, cross-sectional area of the median nerve, and electrophysiological studies. The assessment was performed prior to injection and 1, 3, 4, and 6 months postinjection. RESULTS: All patients (27 wrists per group) completed the study. Compared with the steroid group, the dextrose group exhibited a significant reduction in pain and disability through the 4th to the 6th month (p < 0.01). INTERPRETATION: Our study demonstrates that perineural injection of D5W is more beneficial than that of corticosteroid in patients with mild-to-moderate CTS at 4 to 6 months postinjection. Ann Neurol 2018;84:601-610.

Nerve hydrodissection for carpal tunnel syndrome: A prospective, randomized, double-blind, controlled trial.

INTRODUCTION: In this study we explored the efficacy of nerve hydrodissection for mild-to-moderate carpal tunnel syndrome (CTS). METHODS: Thirty-four participants were randomly assigned to an intervention group or a control group. One 5-ml dose of normal saline was injected into the intracarpal and subcutaneous regions in subjects of both groups, respectively. The primary outcome measure was the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) score. Secondary outcomes were cross-sectional area of the median nerve and electrophysiological studies. Assessments were performed before the injection and at 1, 2, 3, and 6 months postintervention. RESULTS: Compared with the control group, the intervention group showed significantly greater improvement at the second and third posttreatment months according to BCTQ severity score and at all time-points for cross-sectional area of the median nerve (P < 0.01). DISCUSSION: Our study demonstrates the therapeutic effects of nerve hydrodissection for mild-to-moderate CTS. Muscle Nerve 59:174-180, 2019.

New basic insights on the potential of a chitosan-based medical device for improving functional recovery after radical prostatectomy.

OBJECTIVES: To evaluate: (i) the neuro-regenerative potential of chitosan membrane (CS-Me) on acutely axotomised autonomic neurones in vitro; (ii) to exclude the possibility that a pro-regenerative biomaterial could interfere with the proliferation activity of prostate cancer cell lines; (iii) to provide an in vivo proof of the biocompatibility and regeneration promoting effect of CS-Me in a standardised rat model of peripheral nerve injury and repair; (iv) finally, to evaluate the tissue reaction induced by the degrading material; as previous studies have shown promising effects of CS-Me for protection of the neurovascular bundles for potency recovery in patients that undergo nerve-sparing radical prostatectomy (RP). MATERIALS AND METHODS: Addressing aim (i), the neuro-regenerative potential, organotypic cultures derived from primary sympathetic ganglia were cultured on CS-Me over 3 days and neurite extension and axonal sprouting were evaluated. Addressing aim (ii), effects of CS on cancer cells, different human prostate cancer cell lines (PC3, DU-145, LN-Cap) were seeded on CS-coated plates or cultured in the presence of CS-Me dissolution products. Addressing aims (iii) and (iv), functional recovery of peripheral nerve fibres and tissue reaction with the biomaterial, CS-Me and CS nerve guides were used to repair a median nerve injury in the rat. Functional recovery was evaluated during the post-recovery time by the behavioural grasping test. RESULTS: CS-Me significantly stimulated axon elongation from autonomic ganglia in comparison to control conditions in organotypic three-dimensional cultures. CS coating, as well as the dissolution products of CS-Me, led to a significantly lower proliferation rate of prostate cancer cell lines in vitro. Tissue reaction towards CS-Me and standard CS nerve guides was similar in the rat median nerve model, as was the outcome of nerve fibre regeneration and functional recovery. CONCLUSION: The results of this study provide the first experimental evidence in support of the clinical safety of CS-Me and of their postulated effectiveness for improving functional recovery after RP. The presented results are coherent in demonstrating that acutely axotomised autonomic neurones show increased neurite outgrowth on CS-Me substrate, whilst the same substrate reduces prostate cancer cell line proliferation in vitro. Furthermore, CS-Me do not demonstrate any disadvantage for peripheral nerve repair in a standard animal model.

Liraglutide treatment reduced interleukin-6 in adults with type 1 diabetes but did not improve established autonomic or polyneuropathy.

AIMS: Type 1 diabetes can be complicated with neuropathy that involves immune-mediated and inflammatory pathways. Glucagon-like peptide-1 receptor agonists such as liraglutide, have shown anti-inflammatory properties, and thus we hypothesized that long-term treatment with liraglutide induced diminished inflammation and thus improved neuronal function. METHODS: The study was a randomized, double-blinded, placebo-controlled trial of adults with type 1 diabetes and confirmed symmetrical polyneuropathy. They were randomly assigned (1:1) to receive either liraglutide or placebo. Titration was 6 weeks to 1.2-1.8 mg/d, continuing for 26 weeks. The primary endpoint was change in latency of early brain evoked potentials. Secondary endpoints were changes in proinflammatory cytokines, cortical evoked potential, autonomic function and peripheral neurophysiological testing. RESULTS: Thirty-nine patients completed the study, of whom 19 received liraglutide. In comparison to placebo, liraglutide reduced interleukin-6 (-22.6%; 95% confidence interval [CI]: -38.1, -3.2; P = .025) with concomitant numerical reductions in other proinflammatory cytokines. However neuronal function was unaltered at the central, autonomic or peripheral level. Treatment was associated with -3.38 kg (95% CI: -5.29, -1.48; P < .001] weight loss and a decrease in urine albumin/creatinine ratio (-40.2%; 95% CI: -60.6, -9.5; P = .02). CONCLUSION: Hitherto, diabetic neuropathy has no cure. Speculations can be raised whether mechanism targeted treatment, e.g. lowering the systemic level of proinflammatory cytokines may lead to prevention or treatment of the neuroinflammatory component in early stages of diabetic neuropathy. If ever successful, this would serve as an example of how fundamental mechanistic principles are translated into clinical practice similar to those applied in the cardiovascular and nephrological clinic.

Effects of lorazepam and baclofen on short- and long-latency afferent inhibition.

KEY POINTS: Short-latency afferent inhibition (SAI) is modulated by GABAA receptor activity, whereas the pharmacological origin of long-latency afferent inhibition remains unknown. This is the first study to report that long-latency afferent inhibition (LAI) is reduced by the GABAA positive allosteric modulator lorazepam, and that both SAI and LAI are not modulated by the GABAB agonist baclofen. These findings advance our understanding of the neural mechanisms underlying afferent inhibition. ABSTRACT: The afferent volley evoked by peripheral nerve stimulation has an inhibitory influence on transcranial magnetic stimulation induced motor evoked potentials. This phenomenon, known as afferent inhibition, occurs in two phases: short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI). SAI exerts its inhibitory influence via cholinergic and GABAergic activity. The neurotransmitter receptors that mediate LAI remain unclear. The present study aimed to determine whether LAI is contributed by GABAA and/or GABAB receptor activity. In a double-blinded, placebo-controlled study, 2.5 mg of lorazepam (GABAA agonist), 20 mg of baclofen (GABAB agonist) and placebo were administered to 14 males (mean age 22.7 ± 1.9 years) in three separate sessions. SAI and LAI, evoked by stimulation of the median nerve and recorded from the first dorsal interosseous muscle, were quantified before and at the peak plasma concentration following drug ingestion. Results indicate that lorazepam reduced LAI by ∼40% and, in support of previous work, reduced SAI by ∼19%. However, neither SAI, nor LAI were altered by baclofen. In a follow-up double-blinded, placebo-controlled study, 10 returning participants received placebo or 40 mg of baclofen (double the dosage used in Experiment 1). The results obtained indicate that SAI and LAI were unchanged by baclofen. This is the first study to show that LAI is modulated by GABAA receptor activity, similar to SAI, and that afferent inhibition does not appear to be a GABAB mediated process.

Sonographic median nerve change after steroid injection for carpal tunnel syndrome.

INTRODUCTION: The sonographic changes of the median nerve after steroid injection for carpal tunnel syndrome (CTS) still require investigation. METHODS: Sixty-two patients with CTS were included. The Boston Carpal Tunnel Questionnaire was administered, and ultrasonographic examinations were performed before and at 2, 6, and 12 weeks after steroid injection. At 12 weeks, general improvement was scored on a 6-point Likert scale. RESULTS: After treatment, the cross-sectional area (CSA) of the median nerve was significantly reduced at 2-, 6-, and 12-week follow-ups (for each, P < 0.001, analysis of variance). The "significant improvement" group (n = 39) had a significantly greater reduction in the CSA at the carpal tunnel inlet (P = 0.014) and CSA in the proximal carpal tunnel (P = 0.003) compared with the "little/no improvement" group (n = 23). DISCUSSION: Sonographic measurement of CSA may be considered complementary to the standard clinical evaluation in monitoring of treatment response in patients with CTS. Muscle Nerve 58: 402-406, 2018.

Is pharmacologic treatment better than neural mobilization for cervicobrachial pain? A randomized clinical trial.

Purpose: This study aim was to compare the effectiveness of the median nerve neural mobilization (MNNM) and cervical lateral glide (CLG) intervention versus oral ibuprofen (OI) in subjects who suffer cervicobrachial pain (CP). Methods: This investigation was a, multicenter, blinded, randomized controlled clinical trial (NCT02595294; NCT02593721). A number of 105 individuals diagnosed with CP were enrolled in the study and treated in 2 different medical facilities from July to November 2015. Participants were recruited and randomly assigned into 3 groups of 35 subjects. Intervention groups received MNNM or CLG neurodynamic treatments, and the (active treatment) control group received an OI treatment for 6 weeks. Primary outcome was pain intensity reported through the Numeric Rating Scale for Pain (NRSP). Secondary outcomes were physical function involving the affected upper limb using the Quick DASH scale, and ipsilateral cervical rotation (ICR) using a cervical range of motion (CROM) device. Assessments were performed before and 1 hour after treatment for NRSP (baseline, 3 and 6 weeks) and CROM (baseline and 6 weeks), as well as only 1 assessment for Quick DASH (baseline and 6 weeks). Results: Repeated-measures ANOVA intergroup statistically significant differences were shown for CP intensity (F(2,72) = 22.343; P < .001; Eta2 = 0.383) and Quick DASH (F(2,72) = 15.338; P < .001; Eta2 = 0.299), although not for CROM (F(2,72) = 1.434; P = .245; Eta2 = 0.038). Indeed, Bonferroni´s correction showed statistically significant differences for CP intensity (P < .01; 95% CI = 0.22 - 3.26) and Quick DASH reduction (P < .01; 95% CI = 8.48 - 24.67) in favor of the OI treatment at all measurement moments after baseline. Conclusions: OI pharmacologic treatment may reduce pain intensity and disability with respect to neural mobilization (MNNM and CLG) in patients with CP during six weeks. Nevertheless, the non-existence of between-groups ROM differences and possible OI adverse effects should be considered.

Efficacy of Combined Ultrasound-Guided Steroid Injection and Splinting in Patients With Carpal Tunnel Syndrome: A Randomized Controlled Trial.

OBJECTIVE: To compare the effectiveness of local steroid injection plus splinting with that of local steroid injection alone using clinical and electrophysiological parameters in patients with carpal tunnel syndrome (CTS). DESIGN: Randomized controlled study with 12 weeks of follow-up. SETTING: Tertiary care center. PARTICIPANTS: Volunteer sample of patients (N=52) diagnosed with CTS. INTERVENTIONS: Participants were randomly assigned to the steroid injection group (n=26) or the steroid injection-plus-splinting group (n=26). Patients of both groups received ultrasound-guided steroid injection with 1mL of 10mg (10mg/mL) triamcinolone acetonide (Shincort) and 1mL of 2% lidocaine hydrochloride (Xylocaine). Participants in the second group also wore a volar splint in the neutral position while sleeping and also during daytime whenever possible for the 12-week intervention period. MAIN OUTCOME MEASURES: Participants were evaluated before the treatment and at 6 and 12 weeks after the onset of treatment. The primary outcome measure was Boston Carpal Tunnel Questionnaire scores. The secondary outcome measures were as follows: scores on the visual analog scale for pain; electrophysiological parameters, including median nerve distal motor latency, sensory nerve conduction velocity (SNCV), and compound muscle action potential and sensory nerve action potential (SNAP) amplitudes; and patient's subjective impression of improvement. RESULTS: At 12-week follow-up, improvements in symptom severity and functional status scores on the Boston Carpal Tunnel Questionnaire as well as SNCV and SNAP amplitudes were greater in the group that received steroid injection combined with splinting than in the group that received steroid injection alone. The between-group difference was .48 points (95% confidence interval [CI], .09-.88 points; P=.032) in the Symptom Severity Scale score, .37 points (95% CI, .06-.67 points; P=.019) in the Functional Status Scale score, 3.38m/s (95% CI, 0.54-6.22m/s; P=.015) in the SNCV amplitude, and 3.21µV (95% CI, 0.00-6.46µV; P=.025) in the SNAP amplitude. CONCLUSIONS: In people with CTS, steroid injection combined with splinting resulted in modestly greater reduction of symptoms, superior functional recovery, and greater improvement in nerve function at 12-week follow-up as compared with steroid injection alone. However, these small differences are of unclear clinical significance.

Contribution of tactile dysfunction to manual motor dysfunction in type II diabetes.

INTRODUCTION: Changes in sensory and motor functions of the hand in type II diabetes (T2D) patients have been reported; there is speculation that these changes are driven by tactile dysfunction. The purpose of this study was to evaluate the effects of tactile feedback on manual function in T2D patients. METHODS: T2D patients and healthy controls underwent median nerve blocks at the wrist and elbow. All participants underwent traditional timed motor evaluations, force dynamometry, laboratory-based kinetic evaluations, and sensory evaluation. RESULTS: Tactile sensation in the T2D group at baseline was found to be equivalent to tactile function of the control group after median nerve block. Traditional timed evaluation results were negatively impacted by anesthesia, but more sensitive kinetic measures were not impacted. CONCLUSIONS: These data suggest that mechanisms outside of tactile dysfunction play a significant role in motor dysfunction in T2D. Muscle Nerve 54: 895-902, 2016.

Trainee anaesthetist diagnosis of intraneural injection-a study comparing B-mode ultrasound with the fusion of B-mode and elastography in the soft embalmed Thiel cadaver model.

BACKGROUND: The incidence of intraneural injection during trainee anaesthetist ultrasound guided nerve block varies between 16% in experts and up to 35% in trainees. We hypothesized that elastography, an ultrasound-based technology that presents colour images of tissue strain, had the potential to improve trainee diagnosis of intraneural injection during UGRA, when integrated with B-Mode ultrasound onto a single image. METHODS: We recorded 40 median nerve blocks randomly allocated to 0.25 ml, 0.5 ml, 1 ml volumes to five sites, on both arms of two soft embalmed cadavers, using a dedicated B-Mode ultrasound and elastography transducer. We wrote software to fuse elastogram and B-Mode videos, then asked 20 trainee anaesthetists whether injection was intraneural or extraneural when seeing B-Mode videos, adjacent B-Mode and elastogram videos, fusion elastography videos or repeated B-Mode ultrasound videos. RESULTS: Fusion elastography improved the diagnosis of intraneural injection compared with B-Mode ultrasound, Diagnostic Odds Ratio (DOR) (95%CI) 21.7 (14.5 - 33.3) vs DOR 7.4 (5.2 - 10.6), P < 0.001. Compared with extraneural injection, intraneural injection was identified on fusion elastography as a distinct, brighter translucent image, geometric ratio 0.33 (95%CI: 0.16 - 0.49) P < 0.001. Fusion elastography was associated with greater trainee diagnostic confidence, OR (95%CI) 1.89 (1.69 - 2.11), P < 0.001, and an improvement in reliability, Kappa 0.60 (0.55 - 0.66). CONCLUSIONS: Fusion elastography improved the accuracy, reliability and confidence of trainee anaesthetist diagnosis of intraneural injection.

Sonoelastographic Findings of Carpal Tunnel Injection.

PURPOSE: The objectives of this study were to compare sonoelastographic color findings of the perineural area between carpal tunnel syndrome patients and healthy volunteers, and to analyze elastographic findings in that area before and immediately after intracarpal tunnel injection in carpal tunnel syndrome patients. MATERIALS AND METHODS: We studied both hands of 15 healthy volunteers (7 men, 8 women; mean age: 60.1 years, range: 41 - 88 years) and 72 hands from 70 patients with symptomatic carpal tunnel syndrome (24 men, 46 women; mean age: 54.2 years, range: 24 - 83 years). Sonoelastographic color distribution was assessed in the perineural area between the median nerve and adjacent flexor tendons. The color elastograms were graded using the following system: Grade 1 as red (softest), grade 2 as yellow (soft), grade 3 as green (hard), grade 4 as blue (hardest). The patients were treated with corticosteroid injection and were reassessed with sonoelastography immediately after the injection. RESULTS: The median color grading in the perineural area of carpal tunnel syndrome patients was grade 3 (3.1 ±â€Š0.3, mean ±â€Š95 % Cl), which was stiffer than that of healthy volunteers (grade 1, 1.9 ±â€Š0.4) (p < 0.0001). Immediately after injection, the diffusion of the injected fluid was observed as having a softer appearance (grade 1, 1.4 ±â€Š0.2) (p < 0.0001). CONCLUSION: The perineural area surrounding the median nerve in carpal tunnel syndrome patients was stiffer than that in healthy volunteers. Diffusion of the injected fluid in the carpal tunnel was seen as a softer finding after injection in real time using sonoelastography.

High-resolution MRI predicts steroid injection response in carpal tunnel syndrome patients.

OBJECTIVES: To correlate median nerve T2 signal and shape at the carpal tunnel with steroid injection (SI) response in carpal tunnel syndrome (CTS) patients. METHODS: One hundred and sixty-three CTS wrists of 92 consecutive patients who were scheduled to undergo SI were prospectively evaluated with 3-T magnetic resonance imaging (MRI) and a nerve conduction study. All patients underwent axial high-resolution T2-weighted MRI (in-plane resolution of 0.25 × 0.25 mm). The CTS wrists were classified into three groups according to the nerve T2 signal and the flattening ratio at the hook of hamate level: group 1, high and oval; group 2, high and flat; group 3, low and flat. Clinical response to SI was evaluated at 6 months after injection. RESULTS: One hundred and thirteen of the 163 wrists (69.3%) responded well to SI. The percentage of improvement was 81.7% (49/60) in group 1, 69.9% (51/73) in group 2, and 43.3% (13/30) in group 3 (P < 0.01). On stepwise logistic regression analysis high-resolution MRI was the only significant independent factor for SI response in CTS patients (P < 0.01). CONCLUSIONS: High-resolution MRI correlates well with SI response in CTS patients and seems useful for predicting SI response. KEY POINTS: • MRI may help determine appropriate care in carpal tunnel syndrome. • MRI helps in therapeutic decision-making whenever steroid injection is considered. • T2 signal decrease of the median nerve correlates with poor outcome. • T2 signal decrease of median nerve may reflect fibrosis and amyloid deposition.

Ischemic block of the forearm abolishes finger movements but not their associated anticipatory postural adjustments.

Voluntary movement is known to induce postural perturbations that are counteracted by unconscious anticipatory postural adjustments (APAs). Thus, for every movement, two motor commands are dispatched: a voluntary command recruiting the prime mover and a postural command driving the APAs. These commands are classically thought to be separated; this study investigates whether they could be instead considered as two elements within the same motor program. We analyzed the APAs in biceps brachii, triceps brachii and anterior deltoid that stabilize the arm when briskly flexing the index finger (prime mover flexor digitorum superficialis). APAs and prime mover activation were recorded before, under and after ischemic block of the forearm. Ischemia paralyzed the prime mover, thus suppressing the finger movement and the ensuing postural perturbation. If the two commands had been separated, it would have been expected that after a few failed attempts to flex the index finger, the APAs were suppressed too, being purposeless without postural perturbation. APAs were still present under ischemia even after 60 movement trials. No significant changes were found in APA amplitude in biceps and triceps among different conditions, or in the average APA latency. Inhibitory APA in anterior deltoid was reduced but still present under ischemia. In addition, the pharmacologic block of the sole median nerve produced similar effects. APAs were instead almost abolished when applying a fixation point to the wrist. The observation that APAs remained tailored to the expected perturbation even when that perturbation did not occur supports the idea of a functionally unique motor command driving both the prime mover and the muscles of the APA chain.

Melatonin reduces median nerve injury-induced mechanical hypersensitivity via inhibition of microglial p38 mitogen-activated protein kinase activation in rat cuneate nucleus.

In this study, we examined the relationships between p38 mitogen-activated protein kinase (MAPK) activation in the cuneate nucleus (CN) and behavioral hypersensitivity after chronic constriction injury (CCI) of the median nerve. We further investigated effects of melatonin administration and pinealectomy on p38 MAPK activation and development of hypersensitivity. Using immunohistochemistry and immunoblotting, low levels of phosphorylated p38 (p-p38) MAPK were detected in CN of normal rats. As early as 1 day after CCI, p-p38 MAPK levels in the ipsilateral CN were significantly increased (1.4 ± 0.2-fold, P < 0.05), which reached a maximum at 7 days (5.1 ± 0.4-fold, P < 0.001). Double immunofluorescence labeling with cell-specific markers showed that p-p38 MAPK immunoreactive cells co-expressed OX-42, a microglia activation maker, suggesting the expression of p-p38 MAPK in microglia. Microinjection of SB203580, a p38 MAPK inhibitor, into the CN 1 day after CCI attenuated injury-induced behavioral hypersensitivity in a dose-dependent manner. Furthermore, animals received melatonin treatment at daily doses of 37.5, 75, 150, or 300 mg/kg from 30 min before until 3 days after CCI. Melatonin treatment dose-dependently attenuated p-p38 MAPK levels, release of pro-inflammatory cytokines, and behavioral hypersensitivity following CCI; conversely, pinealectomy that resulted in a reduction in endogenous melatonin levels exacerbated these effects. In conclusion, median nerve injury-induced microglial p38 MAPK activation in the CN modulated development of behavioral hypersensitivity. Melatonin supplementation eased neuropathic pain via inhibition of p38 MAPK signaling pathway; contrarily, reducing endogenous blood melatonin levels by pinealectomy promoted phosphorylation of p38 MAPK and made rats more vulnerable to nerve injury-induced neuropathic pain.