Quantification of heat shock proteins in the posterior interosseous nerve among subjects with type 1 and type 2 diabetes compared to healthy controls.

Introduction: Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 (T1D) and type 2 diabetes (T2D). No cure for DPN is available, but several potential targets have been proposed for treatment. Heat shock proteins (HSPs) are known to respond to both hyper- and hypoglycemia. DPN can be diagnosed using electrophysiology and studied using peripheral nerve biopsies. Aim: This study aimed to analyze the presence and patterns of HSPs in peripheral nerve biopsies from subjects with T1D, T2D, and healthy controls. Methods: Posterior interosseous nerves (PIN) from a total of 56 subjects with T1D (n = 9), with T2D (n = 24), and without diabetes (i.e., healthy controls, n = 23) were harvested under local anesthesia and prepared for quantitative mass spectrometry analysis. Protein intensities were associated with electrophysiology data of the ulnar nerve and morphometry of the same PIN, and differences in protein intensities between groups were analyzed. Results: In total, 32 different HSPs were identified and quantified in the nerve specimens. No statistically significant differences were observed regarding protein intensities between groups. Furthermore, protein intensities did not correlate with amplitude or conduction velocity in the ulnar nerve or with the myelinated nerve fiber density of PIN. Conclusion: Quantitative proteomics can be used to study HSPs in nerve biopsies, but no clear differences in protein quantities were observed between groups in this cohort.

Reconstruction of the Distal Oblique Bundle for DRUJ Instability.

Background Treatment algorithm for disruption of the triangular fibrocartilage complex (TFCC) from the ulnar fovea includes direct TFCC repair, tendon reconstruction of the radioulnar ligaments, or a salvage procedure in cases with painful distal radioulnar joint (DRUJ) degeneration. Case Description We describe our surgical technique for reconstruction of the distal oblique bundle (DOB), to attain DRUJ stability in a young man, after failed attempts of direct TFCC reinsertion and radioulnar ligament reconstruction with the Adams procedure. Literature Review Reconstruction of the central band of the interosseous membrane is well recognized for Essex-Lopresti injuries that demonstrate longitudinal forearm instability. The role for reconstruction/reinforcement of the DOB to restore DRUJ stability after TFCC injury has not gained the same recognition and needs further clarification. Clinical Relevance DOB reconstruction technique described is extra-articular and technically straightforward. We believe that the procedure could be considered for patients with an irreparable TFCC injury as a part of the treatment algorithm for younger patients, who otherwise would face a more extensive salvage procedure.

Quantitative proteomic analysis of human peripheral nerves from subjects with type 2 diabetes.

AIMS: Diabetic peripheral neuropathy (DPN) is a common and severe complication to type 2 diabetes. The pathogenesis of DPN is not fully known, but several pathways and gene polymorphisms contributing to DPN are described. DPN can be studied using nerve biopsies, but studies on the proteome of the nerve itself, and its surrounding tissue as a whole, are lacking. Studies on the posterior interosseous nerve (PIN) have proposed PIN a useful indicator of DPN. METHODS: A quantitative mass spectrometry-based proteomics analysis was made of peripheral nerves from age- and gender-matched living human male tissue donors; nine type 2 diabetes subjects, with decreased sural nerve action potentials indicating DPN, and six controls without type 2 diabetes, with normal electrophysiology results. RESULTS: A total of 2617 proteins were identified. Linear regression was used to discover which proteins were differentially expressed between type 2 diabetes and controls. Only soft signals were found. Therefore, clustering of the 500 most variable proteins was made to find clusters of similar proteins in type 2 diabetes subjects and healthy controls. CONCLUSIONS: This feasibility study shows, for the first time, that the use of quantitative mass spectrometry enables quantification of proteins from nerve biopsies from subjects with and without type 2 diabetes, which may aid in finding biomarkers of importance to DPN development.

Vibrotactile sense 5 years after carpal tunnel release in people with diabetes: A prospective study with matched controls.

AIM: To compare vibrotactile sense, 5 years after carpal tunnel release in people with and without diabetes. METHODS: Out of 35 people with diabetes and carpal tunnel syndrome, age- and gender-matched with 31 people without diabetes but with idiopathic carpal tunnel syndrome, 27 and 30 people, respectively, participated in this prolonged follow-up. Vibration perception threshold of the index and little finger (median and ulnar nerve, respectively), 5 years after surgery, was measured at seven different frequencies (8, 16, 32, 64, 125, 250 and 500 Hz). RESULTS: Significant improvement of vibration perception threshold from 1 to 5 years after carpal tunnel release was found at 64 Hz for people with diabetes, while improvement for people without diabetes was demonstrated at several frequencies (64-250 Hz). However, both groups demonstrated a significant decrease in vibration perception threshold for the low frequencies (8-16 Hz). At 5 years, people with diabetes had significantly impaired vibration perception threshold at the index finger for high frequencies (125-500 Hz), and for nearly all frequencies (16 Hz, 64-500 Hz) at the little finger, compared to people without diabetes. CONCLUSION: After carpal tunnel release, significant mid-term improvement of vibrotactile sense appears limited for people with diabetes, compared to a continuous improvement for people without diabetes. In addition, a decline in low-frequency vibrotactile sense occurs for the median as well as the ulnar nerve innervated fingers. Clinical Trial Registration NCT01201109.

Outcome of carpal tunnel release in patients with normal nerve conduction studies.

BACKGROUND: We evaluated outcome after carpal tunnel release (CTR) in patients with clinically diagnosed carpal tunnel syndrome (CTS) but normal results in nerve conduction studies (NCS), and compared these results with those from a prospective group of patients with NCS-verified CTS. METHODS: Over a 5-year period, we prospectively included 103 patients with clinical CTS. NCS were done at inclusion, with surgeon and patient being kept blind regarding the result. The patients underwent endoscopic CTR. QuickDASH and satisfaction score were recorded preoperatively and 4 months after surgery. 94 patients, 47 of whom had NCS-verified CTS, completed the study. RESULTS: A significant improvement in QuickDASH score (18 and 20 points respectively, p < 0.01) was found for both groups. Satisfaction score was significantly higher in the group with NCS-verified CTS. However, the overall satisfaction rates were 87% in the normal NCS group and 95% in the group with abnormal NCS. CONCLUSIONS: Clinical outcome after CTR in patients with normal NCS was favourable and similar to that obtained in patients with NCS-verified CTS. Nonetheless, patients with normal result in NCS gave a lower satisfaction score.

Three-dimensional architecture of human diabetic peripheral nerves revealed by X-ray phase contrast holographic nanotomography.

A deeper knowledge of the architecture of the peripheral nerve with three-dimensional (3D) imaging of the nerve tissue at the sub-cellular scale may contribute to unravel the pathophysiology of neuropathy. Here we demonstrate the feasibility of X-ray phase contrast holographic nanotomography to enable 3D imaging of nerves at high resolution, while covering a relatively large tissue volume. We show various subcomponents of human peripheral nerves in biopsies from patients with type 1 and 2 diabetes and in a healthy subject. Together with well-organized, parallel myelinated nerve fibres we show regenerative clusters with twisted nerve fibres, a sprouted axon from a node of Ranvier and other specific details. A novel 3D construction (with movie created) of a node of Ranvier with end segment of a degenerated axon and sprout of a regenerated one is captured. Many of these architectural elements are not described in the literature. Thus, X-ray phase contrast holographic nanotomography enables identifying specific morphological structures in 3D in peripheral nerve biopsies from a healthy subject and from patients with type 1 and 2 diabetes.

Acute scaphoid fractures: guidelines for diagnosis and treatment.

In cases of suspected scaphoid fracture where the initial radiographs are negative, a supplementary MRI, or alternatively CT, should be carried out within three to five days.Fracture classification, assessment of dislocation as well as evaluation of fracture healing is best done on CT with reconstructions in the coronal and sagittal planes, following the longitudinal axis of the scaphoid.After adequate conservative management, union is achieved at six weeks for approximately 90% of non-displaced or minimally displaced (≤ 0.5 mm) scaphoid waist fractures.Scaphoid waist fractures with moderate displacement (0.5-1.5 mm) can be treated conservatively, but require prolonged cast immobilization for approximately eight to ten weeks.Internal fixation is recommended for all scaphoid waist fractures with dislocation ≥ 1.5 mm.Distal scaphoid fractures can be treated conservatively. The majority heal uneventfully after four to six weeks of immobilization, depending on fracture type.In general, proximal scaphoid fractures should be treated with internal fixation. Cite this article: EFORT Open Rev 2020;5:96-103. DOI: 10.1302/2058-5241.5.190025.

Longitudinal study of neuropathy, microangiopathy, and autophagy in sural nerve: Implications for diabetic neuropathy.

OBJECTIVES: The progression and pathophysiology of neuropathy in impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) is poorly understood, especially in relation to autophagy. This study was designed to assess whether the presence of autophagy-related structures was associated with sural nerve fiber pathology, and to investigate if endoneurial capillary pathology could predict the development of T2DM and neuropathy. PATIENTS AND METHODS: Sural nerve physiology and ultrastructural morphology were studied at baseline and 11 years later in subjects with normal glucose tolerance (NGT), IGT, and T2DM. RESULTS: Subjects with T2DM had significantly lower sural nerve amplitude compared to subjects with NGT and IGT at baseline. Myelinated and unmyelinated fiber, endoneurial capillary morphology, and the presence and distribution of autophagy structures were comparable between groups at baseline, except for a smaller myelinated axon diameter in subjects with T2DM and IGT compared to NGT. The baseline values of the subjects with NGT and IGT who converted to T2DM 11 years later demonstrated healthy smaller endoneurial capillary and higher g-ratio versus subjects who remained NGT. At follow-up, T2DM showed a reduction in nerve conduction, amplitude, myelinated fiber density, unmyelinated axon diameter, and autophagy structures in myelinated axons. Endothelial cell area and total diffusion barrier was increased versus baseline. CONCLUSIONS: We conclude that small healthy endoneurial capillary may presage the development of T2DM and neuropathy. Autophagy occurs in human sural nerves and can be affected by T2DM. Further studies are warranted to understand the role of autophagy in diabetic neuropathy.

Neurophysiological recovery 5 years after carpal tunnel release in patients with diabetes.

INTRODUCTION: The long-term results of neurophysiological recovery after carpal tunnel release in patients with diabetes have not been studied. METHODS: Thirty-five patients with diabetes and carpal tunnel syndrome (CTS) were matched with 31 patients without diabetes who had idiopathic CTS, and 27 and 30 patients, respectively, participated in this follow-up study. Nerve conduction results at 5 years were compared with previously published results at baseline and 1 year. RESULTS: Significant neurophysiological improvement continued from 1 to 5 years after carpal tunnel release for patients with and without diabetes. However, wrist-palm sensory conduction velocity was still abnormal for 85% and 43% of patients with and without diabetes, respectively. Although diabetes had an impact on 4 of 10 measured neurophysiological parameters, the influence of peripheral neuropathy seemed insignificant. DISCUSSION: After carpal tunnel release, significant long-term neurophysiological improvement is possible for patients with diabetes, and it is not influenced by the presence of peripheral neuropathy. Muscle Nerve 56: E59-E64, 2017.

Impact of smoking and preoperative electrophysiology on outcome after open carpal tunnel release.

BACKGROUND: The aim was to evaluate the influence of smoking and preoperative electrophysiology on the outcome of open carpal tunnel release. METHODS: This retrospective observational study evaluated the outcome in 493 patients (531 hands) primary operated for carpal tunnel syndrome. Data were collected from medical records, health evaluations, and QuickDASH questionnaires before surgery and 1 year after. RESULTS: Smokers had a higher QuickDASH score preoperatively as well as postoperatively, but the change in total score did not differ. The odds of having a postoperative QuickDASH score >10 were 2.5 times higher in smoking patients than in non-smoking patients. In 124/493 patients (25%), no clinically significant improvement was seen. Normal and extreme preoperative electrophysiology values were associated with higher postoperative scores. No correlation was found between preoperative QuickDASH scores and preoperative electrophysiology values. CONCLUSIONS: Smokers with carpal tunnel syndrome experience more symptoms preoperatively. Smokers have remaining symptoms after surgery. There is no correlation between preoperative QuickDASH scores and preoperative electrophysiology values. Patients with normal or near to normal preoperative electrophysiology results have limited improvement after surgery.

Outcome after carpal tunnel release: impact of factors related to metabolic syndrome.

OBJECTIVE: The standard surgical treatment of carpal tunnel syndrome (CTS), with an open carpal tunnel release, is reported to relieve symptoms in most patients. In a retrospective observational study, outcome after open carpal tunnel release was evaluated, focusing on factors related to the metabolic syndrome: diabetes, hypertension, obesity (BMI ≥30) and statin treatment. METHODS: Results from 493 out of 962 patients (531/1044 hands) operated for CTS during 18 months that had filled in QuickDASH questionnaires before and 1-year after surgery were included in the study. RESULTS: Patients with diabetes (n = 76) had higher QuickDASH scores pre- (56 [36-77]; i.e. median [interquartile range]) and postoperatively (31 [9-61]) compared to patients without diabetes (48 [32-66]; p < 0.05 and 16 [5-43]; p < 0.001), but the change in total score was equal. A higher proportion of patients with diabetes had a postoperative score of >10 (74% vs 61%; p < 0.05). The odds of having a change in QuickDASH score <8 was 2.6-times higher in patients with polyneuropathy than in patients without polyneuropathy. Patients with hypertension, obesity, or statin treatment had a similar improvement after surgery as patients without these factors. CONCLUSIONS: Patients with diabetes without neuropathy, as well as patients with hypertension, obesity or statin treatment, and CTS can expect the same effects of open carpal tunnel release as otherwise healthy patients. Patients with diabetic neuropathy and CTS did not experience the same improvement as otherwise healthy patients and should be informed about the risk of an unsatisfactory outcome.

Outcome of simple decompression of the compressed ulnar nerve at the elbow - influence of smoking, gender, and electrophysiological findings.

BACKGROUND: Compression of the ulnar nerve at elbow is frequently treated with simple decompression. Knowledge about factors influencing results of surgery of the nerve is limited and contradictory. The primary aim was to evaluate outcome of simple decompression of the nerve using a QuickDASH questionnaire, and to investigate any influence of smoking, gender, and preoperative electrophysiological findings. A second aim was to estimate the relation between QuickDASH score and a clinical assessment of outcome by the surgeon. METHODS: Patients who were operated on with simple decompression of the ulnar nerve, excluding reoperations, from September 2009 to February 2011 were evaluated before and at 1 year after surgery using QuickDASH. Data were collected from medical records and from a self-reported health declaration. RESULTS: There were no differences in QuickDASH scores or change in total score between smokers and non-smokers or between women and men. Nerve pathology, assessed by preoperative electrophysiology, did not affect outcome. The surgeon's assessment of outcome mirrored QuickDASH score. Among all patients, 12/33 (36%) did not have a decrease in QuickDASH score >8, which is considered as a minimal clinically important difference. CONCLUSION: Smoking, gender, and preoperative electrophysiological findings do not affect outcome of surgery. There are a high number of patients who do not benefit from simple decompression of the ulnar nerve at the elbow. Patients who are planned for surgery should be informed that there is a risk for persistent problems. A simple outcome assessment by the surgeon mirrors QuickDASH score at 1 year.

Autophagy in the posterior interosseous nerve of patients with type 1 and type 2 diabetes mellitus: an ultrastructural study.

AIMS/HYPOTHESIS: We addressed the question of whether the autophagy pathway occurs in human peripheral nerves and whether this pathway is associated with peripheral neuropathy in diabetes mellitus. METHODS: By using electron microscopy, we evaluated the presence of autophagy-related structures and neuropathy in the posterior interosseous nerve of patients who had undergone carpal tunnel release and had type 1 or type 2 diabetes mellitus, and in patients with no diabetes (controls). RESULTS: Autophagy-related ultrastructures were observed in the samples taken from all patients of the three groups. The number of autophagy-associated structures was significantly higher (p < 0.05) in the nerves of patients with type 1 than type 2 diabetes. Qualitative and quantitative evaluations of fascicle area, diameter of myelinated and unmyelinated nerve fibres, the density of myelinated and unmyelinated fibres and the g-ratio of myelinated fibres were performed. We found degeneration and regeneration of a few myelinated axons in controls, and a well-developed neuropathy with the loss of large myelinated axons and the presence of many small ones in patients with diabetes. The pathology in type 1 diabetes was more extensive than in type 2 diabetes. CONCLUSIONS/INTERPRETATION: The results of this study show that the human peripheral nerves have access to the autophagy machinery, and this pathway may be regulated differently in type 1 and type 2 diabetes; insulin, presence of extensive neuropathy, and/or other factors such as duration of diabetes and HbA1c level may underlie this differential regulation.

Health-related quality of life 5 years after carpal tunnel release among patients with diabetes: a prospective study with matched controls.

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy encountered in diabetes. The short-term improvement after carpal tunnel release has previously been demonstrated not to differ between patients with and without diabetes, despite a marked impairment in health-related quality of life (HRQL) among the former. In this study, we compare HRQL 5 years after carpal tunnel release between these two groups of patients. METHODS: In a prospective series, 35 patients with diabetes and CTS were matched with 31 control patients with idiopathic CTS but no diabetes. At the 5-year follow-up patients completed the Medical Outcomes Short-Form 36 (SF-36) and Antonovsky's sense of coherence (SOC) questionnaire. Differences in changes over time were compared between patients with and without diabetes using mixed model analysis. RESULTS: Although patients with diabetes reported a significant decrease in physical functioning (p =0.004) as compared to patients without diabetes, postoperative improvement was maintained in the physical domains, role physical and bodily pain. A more pronounced decline in the mental health domain, social function (p =0.03), was demonstrated among patients with diabetes. There was no evidence of any difference in SOC between the patient groups. CONCLUSION: Patients with diabetes retained their improvement in physical domains sensitive to changes after carpal tunnel release in the long-term, despite a decline in other domains of both physical and mental HRQL. This differed from patients without diabetes. Differences in SOC could not explain the sharper decline in these domains among patients with diabetes.

Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome.

AIMS/HYPOTHESIS: We sought to establish the molecular and pathological changes predisposing diabetic and non-diabetic patients to the development of carpal tunnel syndrome (CTS). METHODS: The posterior interosseous nerve (PIN) was biopsied in 25 diabetic and 19 non-diabetic patients undergoing carpal tunnel decompression for CTS. Detailed morphometric and immunohistological analyses were performed in the nerve biopsy. RESULTS: In diabetic patients median nerve distal motor latency was prolonged (p < 0.05 vs non-diabetic patients), PIN myelinated fibre density (p < 0.05), fibre area (p < 0.0001) and axon area (p < 0.0001) were reduced, the percentage of unassociated Schwann cell profiles (p < 0.0001) and unmyelinated axon density (p < 0.0001) were increased and the axon diameter was reduced (p < 0.0001). Endoneurial capillary basement membrane area was increased (p < 0.0001) in diabetic patients, but endothelial cell number was increased (p < 0.01) and luminal area was reduced (p < 0.05) in non-diabetic patients with CTS. There was no difference in the expression of hypoxia-inducible factor 1α between diabetic and non-diabetic patients with CTS. However, the expression of vascular endothelial growth factor A (VEGF) (p < 0.05) and its receptors VEGFR-1 (p < 0.01) and VEGFR-2 (p < 0.05) was significantly increased in diabetic patients, particularly those with type 1 diabetes, and related to the severity of nerve fibre pathology. CONCLUSIONS/INTERPRETATION: This study demonstrates increased nerve fibre and microvascular pathology in relation to enhanced expression of VEGF and its receptors in a non-compressed nerve in diabetic compared with non-diabetic patients with CTS. It therefore provides a potential molecular and pathological basis for the predisposition of diabetic patients to the development of CTS.

Carpal tunnel release in patients with diabetes: a 5-year follow-up with matched controls.

PURPOSE: To compare clinical outcomes 5 years after carpal tunnel release among patients with and without diabetes. METHODS: In a prospective consecutive series, 35 patients with diabetes (median age, 54 y; 15 type 1 and 20 type 2 diabetes) with carpal tunnel syndrome were age- and sex-matched with 31 control patients without diabetes (median age, 51 y) with idiopathic carpal tunnel syndrome. Exclusion criteria were other nerve entrapment, cervical radiculopathy, inflammatory joint disease, thyroid disorder, previous wrist fracture, and long-term exposure to vibrating tools. Participants were examined independently at baseline, 1 year, and 5 years after surgery for sensory function (Semmes-Weinstein), motor function (abductor pollicis brevis muscle strength and grip strength), cold intolerance, and completion of the Boston Carpal Tunnel Questionnaire symptom severity and functional status score. RESULTS: Five years after surgery, the overall attendance rate for clinical examinations and completion of the Boston Carpal Tunnel Questionnaire were 86% and 95%, respectively. Between 1 and 5 years after surgery, there was a tendency toward a decrease in sensory function but an increase in motor function, with no statistically significant difference between groups. Cold intolerance demonstrated long-term significant improvement for patients with diabetes. The improvement in symptom severity and functional status score, as well as the large effect size, were maintained at 5 years in both patient groups. CONCLUSIONS: Long-term improvement in patients with diabetes remained after carpal tunnel release to the same extent as for patients without diabetes. Furthermore, improvement in cold intolerance in patients with diabetes suggests the potential for the long-term regeneration of small nerve fibers. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic I.

The benefit of magnetic resonance imaging for patients with posttraumatic radial wrist tenderness.

PURPOSE: To describe fractures revealed by magnetic resonance imaging (MRI) in a series of skeletally mature patients with radial wrist pain after an acute injury and clinically suspected to have a scaphoid fracture. Additionally, we attempted to assess the diagnostic value of radiographs and computed tomography (CT) in patients with scaphoid and other carpal fractures verified by MRI. METHODS: We conducted the study prospectively over a 3-year period on skeletally mature patients presenting at our emergency department with tenderness on the radial side of the wrist after an injury. A total of 300 wrists in 296 patients underwent clinical and radiographic examination. We performed low-field, 0.23-T MRI of all injured wrists within 3 working days from inclusion in the study. If the radiographs or MRI revealed a scaphoid fracture, we immediately carried out a supplementary 16-slice CT scan of the wrist. We calculated the sensitivity and specificity of radiographs and CT for the diagnosis of scaphoid fractures using MRI as the reference standard. RESULTS: We diagnosed a total of 224 fractures in 196 wrists using MRI; 42% were scaphoid fractures, 15% were distal radius fractures, 6% were triquetrum fractures, and 5% were capitate fractures. The most commonly found fracture combinations were that of the scaphoid and distal radius, followed by scaphoid and capitate fracture. The sensitivity of radiographs for visualization of scaphoid fractures was 70% and the specificity was 98%. Radiographic sensitivity for other fractures was less than 60%. The sensitivity of CT for visualization of scaphoid fractures was 95%, and between 75% and 100% for other fractures. CONCLUSIONS: Low-field MRI showed a high incidence of fractures in patients with posttraumatic radial wrist tenderness and demonstrated more fractures than radiographs and CT. A scaphoid fracture was by far the most common injury. However, it is not clear whether diagnosis of subtle injuries only demonstrated on MRI improves outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic I.