Clinical trials in Charcot-Marie-Tooth disorders: a retrospective and preclinical assessment.

Objective: This study aimed to evaluate the progression of clinical and preclinical trials in Charcot-Marie-Tooth (CMT) disorders. Background: CMT has historically been managed symptomatically and with genetic counseling. The evolution of molecular and pathologic understanding holds a therapeutic promise in gene-targeted therapies. Methods: ClinicalTrials.gov from December 1999 to June 2022 was data extracted for CMT with preclinical animal gene therapy trials also reviewed by PubMed search. Results: The number of active trials was 1 in 1999 and 286 in 2022. Academic settings accounted for 91% and pharmaceutical companies 9%. Of the pharmaceutical and academic trials, 38% and 28%, respectively, were controlled, randomized, and double-blinded. Thirty-two countries participated: the United States accounted for 26% (75/286). In total, 86% of the trials were classified as therapeutic: 50% procedural (21% wrist/elbow surgery; 22% shock wave and hydrodissection therapy), 23% investigational drugs, 15% devices, and 11% physical therapy. Sixty-seven therapeutic trials (49%) were designated phases 1-2 and 51% phases 3-4. The remaining 14% represent non-therapeutic trials: diagnostic testing (3%), functional outcomes (4%), natural history (4%), and standard of care (3%). One-hundred and three (36%) resulted in publications. Phase I human pharmaceutical trials are focusing on the safety of small molecule therapies (n = 8) and AAV and non-viral gene therapy (n = 3). Preclinical animal gene therapy studies include 11 different CMT forms including viral, CRISPR-Cas9, and nanoparticle delivery. Conclusion: Current CMT trials are exploring procedural and molecular therapeutic options with substantial participation of the pharmaceutical industry worldwide. Emerging drug therapies directed at molecular pathogenesis are being advanced in human clinical trials; however, the majority remain within animal investigations.

Efficacy and safety of Tuina for chronic nonspecific low back pain: A PRISMA-compliant systematic review and meta-analysis.

OBJECTIVE: Chronic nonspecific low back pain (CNLBP) is a serious medical and social problem resulting in functional decline and decreased work ability. Tuina, a form of manual therapy, has been sparsely used to treat patients with CNLBP. To systematically assess the efficacy and safety of Tuina for patients with CNLBP. METHODS: Multiple English and Chinese literature databases were searched until September 2022 for randomized controlled trials (RCTs) of Tuina in the treatment of CNLBP. The methodological quality was assessed using the Cochrane Collaboration's tool, and certainty of the evidence was determined with the online Grading of Recommendations, Assessment, Development and Evaluation tool. RESULTS: Fifteen RCTs with 1390 patients were included. Tuina demonstrated a significant effect on pain (SMD: -0.82; 95% CI -1.12 to -0.53; P < .001; I2 = 81%) and physical function (SMD: -0.91; 95% CI -1.55 to -0.27; P = .005; I2 = 90%) when compared to control. However, Tuina resulted in no significant improvement for quality of life (QoL) (SMD: 0.58; 95% CI -0.04 to 1.21; P = .07; I2 = 73%;) compared to control. The Grading of Recommendations, Assessment, Development and Evaluation evidence quality was determined to be low level for pain relief, physical function, and QoL measurements. Only six studies reported adverse events; none were serious. CONCLUSION: Tuina might be an effective and safe strategy for treating CNLBP in terms of pain and physical function, but not for QoL. The study results should be interpreted with caution for their low-level evidence. More multicenter, large-scale RCTs with a rigorous design are required to further confirm our findings.

Platelet-Rich Plasma Injection for Thumb Carpometacarpal Joint Osteoarthritis.

Objective: To assess the effects of platelet-rich plasma (PRP) injection among patients with thumb carpometacarpal (CMC) joint osteoarthritis (OA). Design: Retrospective chart review with follow-up questionnaires/surveys. Post-procedure, patients were sent standardized, automatically-generated follow-up questionnaires, and contacted for a survey regarding patient-reported outcomes. Setting: Single institution (tertiary care hospital) outpatient clinic from 2015 to 2020. Participants: Nineteen adult patients (9 women; average age 65.0 [±6.3 years]) who received a PRP injection for OA of 1 or both thumb CMCs (N=19). Interventions: Platelet-rich plasma injection. Main Outcome Measures: Outcome measures included symptom improvement (subjective, visual analog scale), duration of benefit, subsequent procedures, satisfaction, and side effects/adverse events. Cellular composition of whole blood and PRP injectate (platelets, erythrocytes, leukocytes, neutrophils, lymphocytes, and monocytes) were analyzed. Results: Subjects reported moderate or excellent symptom improvement in 68.8% of injected joints and were moderately or very satisfied with 68.8% of the procedures. Mean patient-reported duration of benefit was 15.6 months (±19.5) months (mean duration of follow-up: 32.4 [±18.1] months). There were no major complications attributed to the procedures, but 1 patient was diagnosed with presumed unrelated lymphoma 2 weeks post-procedure. PRP mean platelet concentration was 1787.77 (±687.14) × 109/L, resulting in a mean platelet concentration factor of 8.80 (±4.19) times baseline and mean platelet dose of 1881 × 106. Other PRP cell concentration factors were erythrocytes, 0.02; neutrophils, 0.14; lymphocytes, 3.76; and monocytes, 3.29. Conclusions: PRP injection appears to be a safe and potentially effective treatment option for pain related to first CMC OA. Further study is needed to optimize treatment protocols and better understand which patients are most likely to benefit.

Passive wrist deviation to increase the ultrasound identified procedural safe zone in carpal tunnel syndrome: A retrospective cohort study.

INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome. Although prior studies have explored the anatomic changes of the median nerve and carpal arch with different wrist deviations and positionings, the change in safe zone distance between the median nerve and ulnar artery with ulnar or radial wrist deviations has not been adequately investigated. OBJECTIVE: To identify the optimal wrist positioning that increases the safe zone distance between the median nerve and ulnar artery using ultrasound in patients with CTS. DESIGN: Retrospective cohort study. SETTING: Quaternary medical center multidisciplinary outpatient hand clinic. PARTICIPANTS: Twenty five patients (41 wrists) with clinical CTS who received an electrodiagnostic study (EDX) to evaluate CTS within 1 year prior to enrollment. INTERVENTIONS: Ultrasound-identified safe zone distance measurements were obtained in each patient between the ulnar aspect of the median nerve and the radial aspect of the ulnar artery with the wrist in neutral radial-ulnar deviation as well as in passive ulnar and radial deviation. MAIN OUTCOME MEASURE: The ultrasound-identified safe zone distance with the wrist in each of the three positions. RESULTS: The interstructural safe zone distance was significantly greater when measured in the ulnarly deviated position (1.08 cm) compared with either the neutral (0.61cm, p < .001) or radially deviated positions (0.52 cm, p < .001). Interstructural safe zone distance did not differ between those with normal, mild, moderate, or severe classifications of pathology, or between dominant and nondominant limbs. CONCLUSION: This study demonstrates that the ultrasound-measured interstructural safe zone distance was significantly greater in the ulnarly deviated position than in either the neutral position or radially deviated position. These findings may lead to improvement in the safety of ultrasound-guided injections.

Utility of Carpal Tunnel Release and Ulnar Decompression in CMT1A and HNPP.

INTRODUCTION/AIMS: Carpal and cubital tunnel syndrome (CTS, CuTS) are common among patients with hereditary neuropathy with liability to pressure-palsies (HNPP) and Charcot-Marie-Tooth type 1A (CMT1A) and may impact quality of life. We aimed to evaluate the utility of nerve decompression surgeries in these patients. METHODS: Medical records were reviewed for patients with PMP22 mutations confirmed in Mayo Clinic laboratories from January 1999 to December 2020, who had CTS and CuTS and underwent surgical decompression. RESULTS: CTS occurred in 53.3% of HNPP and 11.5% of CMT1A, while CuTS was present in 43.3% of HNPP and 5.8% of CMT1A patients. CTS decompression occurred in 10-HNPP and 5-CMT1A patients, and CuTS decompression with/without transposition was performed in 5-HNPP and 1-CMT1A patients. In HNPP, electrodiagnostic studies identified median neuropathy at the wrist in 9/10 patients and ultrasound showed focal enlargements at the carpal and cubital tunnels. In CMT1A, median and ulnar sensory responses were all absent, and the nerves were diffusely enlarged. After CTS surgery, pain, sensory loss, and strength improved in 4/5 CMT1A, and 6/10 HNPP patients. Of clinical, electrophysiologic and ultrasound findings, only activity-provoked features significantly correlated with CTS surgical benefit in HNPP patients (odds ratio = 117.0:95% confidence interval, 1.94 > 999.99, p = 0.01). One CMT1A and one HNPP patient improved with CuTS surgery while 2 HNPP patients worsened. DISCUSSION: CTS symptom improvement post-surgery can be seen in CMT1A and (less frequent) in HNPP patients. CuTS surgery commonly worsened course in HNPP. Activity-provoked symptoms in HNPP best informed benefits from CTS surgery.

Return to work following ultrasound guided thread carpal tunnel release versus open carpal tunnel release: a comparative study.

A retrospective review of hospital employees at a single employer institution who underwent ultrasound guided thread carpal tunnel release (TCTR) or open carpal tunnel release (OCTR) between January 2018 and August 2020 was performed to ascertain differences in return-to-work status. Patient age, sex, occupation, handedness, severity of carpal tunnel syndrome, prior treatments and surgical outcomes were reviewed. A total of 18 patients underwent TCTR and 17 patients underwent OCTR. The TCTR group averaged 12 days to return to work without restrictions, as opposed to 33 days for the OCTR group. Resolution of symptoms was afforded in all patients without any complications regardless of surgical technique. While both TCTR and OCTR were effective, our data indicates that TCTR resulted in a shorter return to work.Level of evidence: III.

Tui Na for Chronic Nonspecific Low Back Pain: Protocol for a Systematic Review and Meta-analysis.

BACKGROUND: Chronic nonspecific low back pain (CNLBP) is one of the most common complex pain conditions, and it is strongly associated with high rates of disability. Even though several studies on Tui na for CNLBP have been reported, to our knowledge there has been no systematic review of the currently available publications. OBJECTIVE: This study aims to develop a protocol for a systematic review and meta-analysis that will evaluate the effectiveness and safety of Tui na therapy for patients with CNLBP. METHODS: An electronic literature search of PubMed, Embase, MEDLINE, Cochrane Library, Springer, Scopus, World Health Organization International Clinical Trials Registry Platform, Physiotherapy Evidence Database (PEDro), Clarivate Analytics, and Chinese biomedical databases (the China National Knowledge Infrastructure, Wan-fang database, Chinese Scientific Journals Database, and Chinese Biomedical Literature Databases) will be conducted. Studies will be screened by two reviewers independently based on titles and abstracts, followed by a full-text reading with eligibility criteria. Randomized controlled trials involving Tui na for patients with CNLBP will be reviewed. The primary outcomes of the study are improvement of pain, analgesic medication reduction, improvement of functional disability, and degree of satisfaction with the intervention. A secondary outcome is any adverse event of Tui na intervention. Methodological quality and risk of bias will be assessed with the Cochrane Collaboration Risk of Bias Tool. If studies are sufficient, a meta-analysis of the effectiveness will be performed. If possible, we will evaluate publication bias using funnel plots. If substantial heterogeneity between studies is present, and there are sufficient studies, subgroup analyses will be conducted to explain the study findings. RESULTS: The review database searches will be initiated in December 2020, with findings expected by January 2021. CONCLUSIONS: This protocol will establish a framework of a high-quality literature synthesis on the impact of Tui na treatment in patients with CNLBP. The proposed review will determine whether Tui na is effective and safe for CNLBP patients. TRIAL REGISTRATION: PROSPERO CRD42020166731; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166731. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/20615.

An Incision-less Ultrasound-guided Carpal Tunnel Release Technique.

Ultrasound guidance in the operative treatment of carpal tunnel syndrome is gaining in popularity as it noninvasively provides the surgeon with a real-time high-resolution overview of anatomic structures. A new incision-less approach to achieve a division of the transverse carpal ligament has been developed that combines ultrasound guidance with cannulated needles and a thread. Conceptually, an abrasive thread is looped percutaneously around the ligament while avoiding injury to neurovascular structures, the palmar aponeurosis, and skin. The thread is positioned using 2 puncture sites and a contoured Tuohy needle under ultrasound visualization. With a minimal injury to surrounding structures, this approach is designed to minimize recovery time and decrease pillar pain. This article will provide a step-by-step overview of the technique and includes a review of clinical outcomes published so far.

Ultrasound-Guided Hydrodissection With Corticosteroid Injection in the Treatment of Carpal Tunnel Syndrome: A Pilot Study.

OBJECTIVES: Corticosteroid injections can provide (temporary) relief in patients with mild to moderate carpal tunnel syndrome (CTS). Hydrodissection as part of an injection has been associated with positive clinical outcomes but data for CTS so far has been scarce. This study is designed to assess patient tolerance and secondarily provide pilot data on the added effect of hydrodissection. METHODS: Twenty CTS patients were randomized to an ultrasound-guided betamethasone injection with hydrodissection (5 mL) or without (2 mL). Patient tolerance was assessed directly after intervention and patient-reported outcome after 4 and 24 weeks. Intra-group data were compared using Wilcoxon Signed Rank and inter-group with Wilcoxon rank-sum tests. RESULTS: Tolerance and pain scores did not differ between the two groups. Symptom scores decreased in both groups, but to a lesser extent in the hydrodissection group with a mean difference of -0.8 versus -1.5 in the control group at 4 weeks (P = .02). At 6 months, this difference was no longer present (P = .81). No statistically significant differences were found between the hydrodissection and control groups in the function or pain scores at follow-up at either time point. CONCLUSION: After injection, both symptomatic and functional scores improved, but the hydrodissected group did not show additional improvement. Data presented can be used to support larger studies to assess the value of hydrodissection in CTS management.

Botox and Thumb MCP Radial Collateral Ligament Reconstruction.

Background We report the use of botulinum toxin to aid in the treatment of chronic radial collateral ligament insufficiency of the thumb. Case Description Treatment included autograft tendon reconstruction and cast immobilization. Six weeks postoperatively, prior to hand therapy, the patient underwent an ultrasound-guided botulinum neurotoxin A injection into the adductor pollicis muscle to negate its deforming forces on the reconstruction. The patient made an excellent recovery and 1 year postoperatively was pain free and had a stable radial collateral ligament (RCL) upon examination. Literature Review The outcomes of RCL repair and reconstruction are unpredictable, in part, due to the strong opposing forces of the adductor pollicis. Clinical Relevance The use of Botox injection may enhance the outcomes of RCL repair or reconstruction by neutralizing the deforming forces of the adductor muscle.

Ultrasound elastography: the new frontier in direct measurement of muscle stiffness.

The use of brightness-mode ultrasound and Doppler ultrasound in physical medicine and rehabilitation has increased dramatically. The continuing evolution of ultrasound technology has also produced ultrasound elastography, a cutting-edge technology that can directly measure the mechanical properties of tissue, including muscle stiffness. Its real-time and direct measurements of muscle stiffness can aid the diagnosis and rehabilitation of acute musculoskeletal injuries and chronic myofascial pain. It can also help monitor outcomes of interventions affecting muscle in neuromuscular and musculoskeletal diseases, and it can better inform the functional prognosis. This technology has implications for even broader use of ultrasound in physical medicine and rehabilitation practice, but more knowledge about its uses and limitations is essential to its appropriate clinical implementation. In this review, we describe different ultrasound elastography techniques for studying muscle stiffness, including strain elastography, acoustic radiation force impulse imaging, and shear-wave elastography. We discuss the basic principles of these techniques, including the strengths and limitations of their measurement capabilities. We review the current muscle research, discuss physiatric clinical applications of these techniques, and note directions for future research.

Accuracy of sonographically guided and palpation guided scaphotrapeziotrapezoid joint injections.

OBJECTIVES: The purpose of this study was to determine and compare the accuracies of sonographically guided and palpation guided scaphotrapeziotrapezoid (STT) joint injections in a cadaveric model. METHODS: A clinician with 6 years of experience performing sonographically guided procedures injected 1.0 mL of a diluted latex solution into the STT joints of 20 unembalmed cadaveric wrist specimens using a palmar approach. At a minimum of 24 hours after injection, an experienced clinician specializing in hand care completed palpation guided injections in the same specimens using a dorsal approach and 1 mL of a different-colored latex. A fellowship-trained hand surgeon blinded to the injection technique then dissected each specimen to assess injection accuracy. Injections were graded as accurate if the colored latex was found in the STT joint, whereas inaccurate injections resulted in no latex being found in the joint. RESULTS: All sonographically guided injections were accurate (100%; 95% confidence interval, 81%-100%), whereas only 80% of palpation guided injections were accurate (95% confidence interval, 61%-99%). Sonographically guided injections were significantly more accurate than palpation guided injections, as determined by the ability to deliver latex into the joint (P < .05). CONCLUSIONS: Sonographic guidance can be used to inject the STT joint with a high degree of accuracy and is more accurate than palpation guidance within the limits of this study design. Clinicians should consider using sonographic guidance to perform STT joint injections when precise intra-articular placement is desired. Further clinical investigation examining the role of sonographically guided STT joint injections in the treatment of patients with radial wrist pain syndromes is warranted.

Ultrasound-guided thoracic facet injections: description of a technique.

OBJECTIVES: The purpose of this study was to describe a technique using ultrasound guidance to perform thoracic facet joint injections. METHODS: A single examiner used ultrasound to localize paired thoracic facet joints from T1-2 through T10-11 on a fresh frozen cadaveric specimen. This was done using a 2- to 5-MHz curvilinear transducer over the target facet in the sagittal plain with the cadaver in the prone position. Target facets were identified using the most inferior rib as a starting point and scanning medially toward its axial attachment and further medially and slightly superior over the most caudal thoracic facet (T11-12). Subsequent ipsilateral facet joints were identified by simply moving the transducer superiorly in the sagittal plain until the next cephalad facet was encountered. After identification, injections were performed using a long-axis or "in-line" approach with continual visualization of the needle into each facet joint. After needle placement, computed images were obtained from a fluoroscopy machine capable of 3-dimensional reconstruction to assess the location of the needle tips. After this, 0.5 mL of an iodinated contrast agent was injected, and another 3-dimensional reconstruction was performed to assess the location of the injected agent. A senior radiology resident reviewed the computed images in coronal, axial, and sagittal planes. Accuracy was determined in terms of contrast location, graded as either intra-articular or extra-articular. RESULTS: Sixteen (80%) of 20 injections performed showed intra-articular contrast spread. CONCLUSIONS: We describe a relatively feasible technique for performing thoracic facet joint injections using ultrasound guidance. Further verification of this technique, and modification if applicable, should be performed before directly applying this technique in a clinical practice setting.

An unusual presentation of acute calcific tendinitis in the hand.

Acute calcific tendinitis (ACT) is a relatively uncommon disorder of the hand and wrist. ACT is a well-known condition of the shoulder, but it often goes unrecognized when occurring in the hand or wrist. The overall lack of familiarity along with the non-specific symptoms associated with ACT frequently leads to misdiagnosis or delay in diagnosis. We report a case of acute calcific tendinitis occurring in the carpal tunnel which is a rare presentation.

Digital ischemia after carpal tunnel injection: a case report.

A 51-year-old woman described paresthesias in her right thumb, index, and middle fingers consistent with carpal tunnel syndrome. Using a sterile technique, a 25-G, 1 1/4-in needle was introduced ulnar to the palmaris longus tendon, and a mixture of 1.5 mL of 40 mg/mL of triamcinolone acetonide and 1.5 mL of 1% lidocaine was injected. After the injection, the patient's hand exhibited signs of ischemia including coolness and discoloration. Rewarming of the hand with paraffin was performed immediately, and normative color returned. At follow-up visits, the patient described burning in the hand, and blotchiness of the digits was noted. A magnetic resonance imaging angiogram of the right wrist showed a single deep palmar arch. Electromyography and nerve conduction study weeks after the injection showed bilateral median neuropathies, moderately severe on the right and mild on the left. She underwent an open carpal tunnel release 6 weeks postinjection. The patient did well and returned to her job without restrictions. The exact etiology of the hand ischemia is unclear but may be related to vasospasm as has been described in the spine-injection literature. Regardless of the etiology, this case shows an uncommon adverse event in a commonly performed procedure and raises questions for further review.

Evidence-informed management of chronic low back pain with traction therapy.

The management of chronic low back pain (CLBP) has proven to be very challenging in North America, as evidenced by its mounting socioeconomic burden. Choosing among available nonsurgical therapies can be overwhelming for many stakeholders, including patients, health providers, policy makers, and third-party payers. Although all parties share a common goal and wish to use limited health-care resources to support interventions most likely to result in clinically meaningful improvements, there is often uncertainty about the most appropriate intervention for a particular patient. To help understand and evaluate the various commonly used nonsurgical approaches to CLBP, the North American Spine Society has sponsored this special focus issue of The Spine Journal, titled Evidence-Informed Management of Chronic Low Back Pain Without Surgery. Articles in this special focus issue were contributed by leading spine practitioners and researchers, who were invited to summarize the best available evidence for a particular intervention and encouraged to make this information accessible to nonexperts. Each of the articles contains five sections (description, theory, evidence of efficacy, harms, and summary) with common subheadings to facilitate comparison across the 24 different interventions profiled in this special focus issue, blending narrative and systematic review methodology as deemed appropriate by the authors. It is hoped that articles in this special focus issue will be informative and aid in decision making for the many stakeholders evaluating nonsurgical interventions for CLBP.