Progression and regression of nerve fibre pathology and dysfunction early in diabetes over 5 years

It has been traditionally suggested that the early development of diabetic sensorimotor polyneuropathy (DSPN) is characterized by a predominant and progressive injury to small nerve fibres followed by large fibre impairment. We alternatively hypothesized that small and large fibre damage due to DSPN in type 1 and type 2 diabetes could develop in parallel and may not only be progressive but also reversible. Participants from the German Diabetes Study baseline cohort with recent-onset type 1/type 2 diabetes (n = 350/570) and age-matched glucose-tolerant control individuals (Control 1/Control 2: n = 114/190) were assessed by nerve conduction studies (NCS), thermal detection thresholds (TDT), vibration perception threshold (VPT), Neuropathy Symptom Score (NSS), Neuropathy Disability Score (NDS), and intraepidermal nerve fibre density (IENFD) in skin biopsies (type 1/type 2 diabetes: n = 102/226; Control 1/Control 2: n = 109/208). Subsets of participants with type 1/type 2 diabetes were followed for 5 years (n = 184/307; IENFD subset: n = 18/69). DSPN was defined by the Toronto Consensus criteria. At baseline, DSPN was present in 8.1 and 13.3% of the type 1 and type 2 diabetes groups, respectively. The most frequently abnormal tests in the lower limbs below or above the 2.5th and 97.5th centile of the controls were IENFD (13.7%) and individual NCS (up to 9.4%) in type 1 diabetes participants and IENFD (21.8%), malleolar VPT (17.5%), and individual NCS (up to 11.8%) in those with type 2 diabetes, whereas TDT abnormalities did not differ between the control and diabetes groups. After 5 years in type 2 diabetes participants, the highest progression rates from the normal to the abnormal range were found for IENFD (18.8%) by -4.1 ± 2.8 fibres/mm, malleolar VPT (18.6%) by 9.1 ± 20.2 µm, and NDS (15.0%) by 3.7 ± 1.5 points, while vice versa the highest regression rates were observed for NDS (11.2%) by -3.1 ± 1.3 points, sural nerve amplitude (9.1%) by 4.7 ± 3.0 µV, IENFD (8.7%) by 1.4 ± 1.3 fibres/mm, and NSS (8.2%) by -5.8 ± 1.6 points. In type 1 diabetes participants, no major progression was seen after 5 years, but subclinical DSPN regressed in 10.3%. These findings point to an early parallel damage to both small and large nerve fibres in well-controlled recent-onset type 2 and, to a lesser extent, type 1 diabetes. After 5 years peripheral nerve morphology and function and clinical measures progress to the abnormal range in type 2 diabetes, but initial nerve alterations are also reversible to a meaningful degree.

Adaptation and compensation for somatosensory deficits in object handling: evidence from a patient with large fibre sensory neuropathy

The purpose of this study was to determine the contributions of feedforward and feedback processes on grip force regulation and object orientation during functional manipulation tasks. One patient with massive somatosensory loss resulting from large fibre sensory neuropathy, and ten control participants were recruited. Three experiments were conducted: 1) perturbation to static holding; 2) discrete vertical movement; and 3) functional grasp and place. The availability of visual feedback was also manipulated to assess the nature of compensatory mechanisms. Results from experiment 1 indicated that both the deafferented patient and controls used anticipatory grip force adjustments prior to self-induced perturbation to static holding. The patient exhibited increased grip response time, but the magnitude of grip force adjustments remained correlated with perturbation forces in the self-induced and external perturbation conditions. In experiment 2, the patient applied peak grip force substantially in advance of maximum load force. Unlike controls, the patient's ability to regulate object orientation was impaired without visual feedback. In experiment 3, the duration of unloading, transport and release phases were longer for the patient, with increased deviation of object orientation at phase transitions. These findings show that the deafferented patient uses distinct modes of anticipatory control according to task constraints, and that responses to perturbations are mediated by alternative afferent information. The loss of somatosensory feedback thus appears to impair control of object orientation, while variation in the temporal organization of functional tasks may reflect strategies to mitigate object instability associated with changes in movement dynamics.

Adverse health manifestations in the hands of vibration exposed carpenters - a cross sectional study

Background Despite EU regulatory standards, many workers suffer injury as a result of working with hand-held vibrating tools. Our aim of this study was to confirm whether carpenters, a highly exposed group, suffer more injuries to their hands than painters, a group assumed to be less exposed to vibration. Methods 193 carpenters (participation rate 100%) and 72 painters (participation rate 67%), all men, answered a questionnaire and underwent a clinical examination to identify manifestations of neural and vascular origin in the hands. Neurosensory affection was defined as having at least one symptom in the fingers/hands (impaired perception of touch, warmth, or cold, impaired dexterity, increased sensation of cold, numbness or tingling, or pain in the fingers/hands when cold) and at least one clinical finding (impaired perception of touch, warmth, cold, vibration, or two-point discrimination). Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Results Neurosensory affection was fulfilled for 31% of the carpenters and 17% of the painters, age-adjusted OR 3.3 (CI 1.6–7.0). Among carpenters with neurosensory affection 18% reported interference with daily life activities, the most common symptoms being increased sensation of cold, numbness and pain in the fingers/hands when cold, the most common clinical findings were impaired perception of touch and vibration. Neurosensory affection was found in 12% of young carpenters (≤ 30 years old). No difference was found in the prevalence of white fingers between carpenters and painters. Conclusions Carpenters showed more symptoms and clinical findings of neurosensory affection than painters, probably due to vibration exposure. Also young carpenters showed signs of neurosensory affection, which indicates that under current conditions workers at these companies are not protected against injury. This underlines the importance of reducing exposure to vibration and conducting regular medical check-ups to detect early signs of neural and vascular manifestations indicating hand-arm vibration injuries. Special attention should be given to symptoms of increased sensation of cold, pain in the fingers when cold, and numbness, as these were the most common initiating ones, and should be addressed as early as possible in the preventive sentinel process. It is also important to test clinically for small- and large-fibre neuropathy, as the individual may be unaware of any pathology.

Adverse Health Manifestations in the Hands of Vibration Exposed Carpenters - A Cross Sectional Study

BackgroundDespite EU regulatory standards, many workers suffer injury as a result of working with hand-held vibrating tools. Our aim of this study was to investigate whether carpenters, a highly exposed group, suffer more injuries to their hands than painters, a group assumed to be less exposed to vibration. Methods193 carpenters and 72 painters, all men, answered a questionnaire and underwent a clinical examination to identify manifestations of neural and vascular origin in hands. Neurosensory affection was defined as having at least one symptom in the fingers/hands (impaired perception of touch, warmth, or cold, impaired dexterity, increased sensation of cold, numbness or tingling, or pain in the fingers/hands when cold) and at least one clinical finding (impaired perception of touch, warmth, cold, vibration, or two-point discrimination). Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). ResultsNeurosensory affection was fulfilled for 31% of the carpenters and 17% of the painters, age-adjusted OR 3.3 (CI 1.6–7.0). Among carpenters with neurosensory affection 18% reported interference with daily life activities, the most common symptoms being increased sensation of cold, numbness and pain in the fingers/hands when cold, the most common clinical findings were impaired perception of touch and vibration. Neurosensory affection was found in 12 % of young carpenters (≤ 30 years old). No difference was found in the prevalence of white fingers between carpenters and painters. ConclusionsCarpenters showed more symptoms and clinical findings of neurosensory affection than painters, probably due to vibration exposure. Also young carpenters showed signs of neurosensory affection, which indicates that workers at today´s working conditions are not protected against injury. This underlines the importance of reducing exposure to vibration, and conducting regular medical check-ups to detect early signs of neural and vascular manifestations indicating hand-arm vibration injuries. Special attention should be given to symptoms of increased sensation of cold, pain in the fingers when cold, and numbness, as these were the most common initiating ones, and should be addressed as early as possible in the preventive sentinel process. It is also important to test clinically for small- and large-fibre neuropathy, as the individual may be unaware of any pathology.

Wuhan lockdown will leave mark on China’s tech sector

Subject The impact of the Wuhan COVID-19 lockdown on China's high-tech development plans. Significance The city of Wuhan -- the origin and epicentre of the COVID-19 epidemic, and target of the country’s longest and most severe lockdown -- plays a significant role in the China’s Made In China 2025 plan to develop indigenous high-tech industries. Impacts Wuhan will suffer long-lasting stigma as the origin of COVID-19, which may affect its ability to compete with other tech hubs for talent. The city’s large fibre-optic sector may in the long run lose out from efforts by customers to diversify their suppliers. Tech firms are likely to be made a priority in government recovery spending. Key people in strategic sectors may have got priority medical treatment, but COVID-19 may still adversely affect the high-tech workforce.

Large Fibre Neuropathy: Part of Fibromyalgia or Coexisting Entity?

Zusammenfassung Zielsetzung Ziel dieser Studie ist es, die Inzidenz von Large Fibre Neuropathy (LFN) bei Fibromyalgie (FM) -Patienten mit peripheren Neuropathie-Beschwerden zu untersuchen und den Einfluss von LFN und FM auf Schmerzen, Lebensqualität, Schlafqualität, Behinderung, und depressive Symptome. Methoden Zwischen Juni 2018 und Februar 2019 wurden insgesamt 104 Patienten (67 Frauen, 37 Männer; Durchschnittsalter: 52,21±9,53 Jahre; Spanne 31–74 Jahre) mit der Diagnose FM in die Studie eingeschlossen. Die Patienten wurden in 2 Gruppen eingeteilt: Gruppe 1, einschließlich Patienten mit Polyneuropathie (PNP) (n=48) und Gruppe 2, einschließlich Nicht-PNP-Patienten (n=54). Gruppe 1 wurde auch weiter in 2 Untergruppen als sensorische PNP (n=28) und sensomotorische PNP (n=20) unterteilt. Alle Patienten wurden anhand der Visual Analog Scale (VAS), des Fibromyalgia Impact Questionnaire (FIQ), des Short Form-36 (SF-36), des Pittsburgh Sleep Quality Index (PSQI) und des Beck Depression Inventory (BDI) bewertet. Ergebnisse Es gab keinen statistisch signifikanten Unterschied in den demografischen Merkmalen zwischen den Gruppen (p>0,05). Es gab einen statistisch signifikanten Unterschied in den VAS-, SF-36-, BDI-, FIQ- und PSQI-Werten zwischen Gruppe 1 und Gruppe 2 (p<0,05). Es gab keinen statistisch signifikanten Unterschied in den VAS-, SF-36-, BDI-, FIQ- und PSQI-Werten zwischen den sensorischen und sensomotorischen PNP-Gruppen (p>0,05). Schlussfolgerungen Unsere Studienergebnisse zeigen, dass FM mit LFN die Schmerzen, die Lebensqualität, die Schlafqualität, die Behinderung und die depressiven Symptome negativ beeinflusst, gegenüber denjenigen ohne LFN, was auf die Bedeutung des Neuropathiemanagements bei FM-Patienten hinweist.

Neurotoxicity of bupivacaine and liposome bupivacaine after sciatic nerve block in healthy and streptozotocin-induced diabetic mice

Background Diabetes mellitus and the associated neuropathic complications have become a steadily increasing global health burden. Diabetic patients are estimated to require surgery at least twice as often as nondiabetic patients. Neuropathy may change the way nerves respond to nerve blocks. There is currently no consensus on whether regional anaesthesia techniques should be adopted in these patients. Long-acting local anaesthetics ( e.g . bupivacaine HCl) or sustained-release formulations of bupivacaine ( e.g . liposomal bupivacaine) could prove neurotoxic in the presence of diabetic neuropathy. The aim of the study was to assess neurotoxicity of liposome bupivacaine in streptozotocin (STZ)-induced diabetic mice after sciatic nerve block using a reduction in fibre density and decreased myelination assessed by G-ratio as an indicator of local anaesthetic neurotoxicity. Results Prior to performing sciatic nerve block, higher levels of fasting glucose were recorded in diabetic mice compared to nondiabetic mice ( P < 0.001). Likewise, significant differences were noted in the tail flick and plantar test thermal latencies between the groups ( P < 0.001) which confirmed the presence of peripheral sensory neuropathy in diabetic mice. In both, diabetic and nondiabetic mice, sciatic nerve block with 0.25% bupivacaine HCl resulted in a significantly greater G-ratio (axon diameter/large fibre diameter) and an axon diameter compared to nerves treated with 1.3% liposomal bupivacaine or saline (0.9% sodium chloride) ( P < 0.01 ). Moreover, sciatic nerve block with 0.25% bupivacaine HCl resulted in higher fibre density and large fibre and axon diameters compared to the control (untreated) sciatic nerves in both STZ-induced diabetic ( P < 0.05 ) and nondiabetic mice ( P < 0.01 ). No evidence of acute or chronic inflammation was observed in any of the treatment groups. Conclusions Under the conditions of this study, sciatic nerve block with bupivacaine HCl, but not liposome bupivacaine or saline, resulted in histomorphometric indices of neurotoxicity. The presence of diabetes did not appear to affect the severity of the histologic findings.