Persistent Neuropathy in Lepromatous Leprosy Patients

Lepromatous leprosy (LL) patients have evidence of extensive peripheral nerve damage as soon as a diagnosis is made, but most of them have few or no symptoms related to peripheral neuropathy. Usually, they do not have the cardinal signal of leprosy neuritis. However, disability caused by peripheral nerve injuries has consequences throughout the entire life of these patients and the pathophysiological mechanisms of nerve damage are still poorly understood. The objective of this study was to evaluate the outcome of peripheral neuropathy in a group of LL patients in an attempt to understand the mechanisms of nerve damage. We evaluated medical records of 14 LL patients that had undergone a neurological evaluation at the beginning of Leprosy treatment then worsened at least 4 years after the end of treatment and underwent nerve biopsy. The symptoms at the beginning of treatment were compared with those at the time of the biopsy. Pain was a symptom in only one patient at the beginning and was a complaint in 9 patients by the time of biopsy. Neurological examination showed that the majority of patients already had alterations in medium and large caliber fibers at the beginning of the treatment, and pain increased by the time of biopsy, while neurological symptoms and signs deteriorated independently of the use of prednisone or thalidomide. Nerve Conduction Studies demonstrated that sensory nerves were the most affected. LL patients can develop a silent progressive degenerative peripheral neuropathy, which continues to develop despite high dose long term corticoid therapy.

Clinical and electromyography characteristics of chemotherapy-induced polyneuropathy in children with acute lymphoblastic leukemia

Background. The Hemoblastoses are one of the urgent problems of oncohematology. Modern methods for the treatment of hemoblastoses have improved the prognosis significantly. However, the use of chemotherapy is accompanied by a high frequency of drug complications, including those associated with neurotoxicity. The addition of neurological symptoms to the main clinical picture of the disease significantly aggravates the patients condition, affects the prognosis and quality to life. Aim. Compare clinical picture and neurophysiological signs of chemo-induced polyneuropathy in children with acute lymphoblastic leukemia. Materials and methods. Neurological examination and electromyography (EMG), were conducted in 21 children aged 3 to 17 years in Regional Children Clinical Hospital of Yekaterinburg from 2019 to 2020. Results. In the study group, the signs of peripheral polyneuropathy, were revealed in almost all patients receiving induction chemotherapy (95.2%) while clinical neurological symptoms were found in 25% patients. During a 4-month follow-up, all children with subclinical signs of peripheral nerve damage developed corresponding neurological symptoms. According to EMG, the number of patients with mixed polyneuropathy increased by 1.7 times. In every third child, the amplitude of the M-response and nerve conduction velocity, were decreased. Conclusions. Therefore, neurophysiological examination should be performed at an early stage to identify high-risk groups for neurotoxic complications in children with acute lymphoblastic leukemia receiving chemotherapy as timely administration of therapeutic treatment is required.

Tactics of Surgical Treatment of Wounded with Gunshot Injuries of the Upper Limb in Modern Conditions

Summary. Our study aimed to optimize the tactics of surgical treatment of wounded with gunshot wounds of the upper extremity by determining the factors influencing the outcome of treatment of servicemen in modern conditions of specialized and highly specialized medical care. Materials and Methods. Surgical treatment of 123 patients with gunshot wounds of the upper extremity who were treated at the SI “Institute of Traumatology and Orthopedics of NAMS of Ukraine” and the National Military Medical Clinical Center “Main Military Clinical Hospital” of the Ministry of Defense of Ukraine was analyzed. The mean age of patients was (35.3±8.7). At the level III of medical care, the largest share was occupied by wound closure (28.0%) and surgeries on the skeletal system (6.7%). At the level IV of medical care, the largest share was occupied by surgical procedures for closing unhealed wounds – 28%, due to the consequences of gunshot nerve injuries – 11.5%, fractures – 10.7%, and restorative interventions on muscles – 5.5%. Results. By calculating the odds ratio (Odds Ratio, OR), it was found that the presence of compartment syndrome reduces the probability of obtaining a positive result by 11 times (OR=11.3), and late treatment at the level IV of care reduces the effectiveness of treatment by 9 times (OR=9.1). In the group of patients with peripheral nerve damage, satisfactory results were 6.9 times less than in the group without such damage (OR=6.9); the presence of a tissue defect worsened the prognosis of treatment by almost 5 times (OR=4.7). The average time to start surgical treatment after a gunshot wound was 2.8±5.0 days at the level III and 47.2±70.4 days at the level IV. It was found that for patients admitted to the level IV facilities for up to 30 days, the percentage increase in upper extremity function was 42.6±11.8 after treatment and 28.5±10.0 at a later start of treatment. Conclusions. The results of the study of the factors influencing the outcome of treatment prove the need for early (up to 3 weeks) admission of wounded with gunshot wounds to the level IV of medical care.

Diffculties and ways to overcome them in selection of therapy for pain syndromes in patients with diabetes mellitus

Diabetes mellitus (DM) causes damage to various body systems, including the peripheral nervous system. The main variants of peripheral nerve damage in diabetes mellitus are considered. Information on the development of this kind of lesion, in particular, on the formation of neuropathic pain syndrome, is given. The therapeutic possibilities of drugs from various pharmacological groups for the treatment of patients with neurological complications of diabetes are analyzed.

Intrinsic positional memory guides target-specific axon regeneration in the zebrafish vagus nerve

ABSTRACT Regeneration after peripheral nerve damage requires that axons re-grow to the correct target tissues in a process called target-specific regeneration. Although much is known about the mechanisms that promote axon re-growth, re-growing axons often fail to reach the correct targets, resulting in impaired nerve function. We know very little about how axons achieve target-specific regeneration, particularly in branched nerves that require distinct targeting decisions at branch points. The zebrafish vagus motor nerve is a branched nerve with a well-defined topographic organization. Here, we track regeneration of individual vagus axons after whole-nerve laser severing and find a robust capacity for target-specific, functional re-growth. We then develop a new single-cell chimera injury model for precise manipulation of axon-environment interactions and find that (1) the guidance mechanism used during regeneration is distinct from the nerve's developmental guidance mechanism, (2) target selection is specified by neurons' intrinsic memory of their position within the brain, and (3) targeting to a branch requires its pre-existing innervation. This work establishes the zebrafish vagus nerve as a tractable regeneration model and reveals the mechanistic basis of target-specific regeneration.

Litigation in Anesthesia and Intensive Care Units: An Italian Retrospective Study

Anesthesiologists consider professional insurance and its medico-legal problems as a remarkable aspect of their job. “Associazione Anestesisti Rianimatori Ospedalieri Italiani—Emergenza ed Area Critica” (AAROI-EMAC) is the Italian professional association of anesthesiologists and intensivists that works to train its subscribers on safety measures. This is a retrospective observational study on an insurance complaints database for anesthetic accidents that result in injuries to patients. The analyzed period runs from 1 January 2014 to 31 December 2016. A total of 1309 complaints related to 873 insurance claims were analyzed. Criminal complaints comprised 805 (64.4%) of the total, and civil complaints were 445 (35.6%). The iatrogenic damage claimed included: death (58% of the cases); peripheral nerve damage (8%); spinal cord injuries (5%); unspecified injuries (7%); dental damage (4%); infections (3%); needing second surgical procedure (2%); and other injuries (13%). There is a statistical significance between the size of the hospital and the number of the claims: small hospital complaints comprised 40.1% of the cases, while complaints against medium-sized and large hospitals constituted 20.6% of the cases (χ2GL = 8 = 39.87, p = 0.00). In Italy, anesthesiologists and intensivists are often involved in litigation even when they are not directly responsible for iatrogenic injuries, and the most frequent claims in ICU are related post-operative complications.

Intraoperative infrared fluorescence angiography in surgery of peripheral nerve injuries

Often, when performing reconstruction of nerve trunks, between the ends of the damaged nerve, the presence of diastasis is noted, which requires significant nerve tension in order to overcome it. This, in turn, can lead to a violation of the blood supply to the nerve and damage to its ultrastructures, which leads to unsatisfactory treatment results. The possibility of using intraoperative infrared fluorescence angiography in reconstructive surgical interventions for peripheral nerve damage, in order to assess the degree of blood flow disturbance in the nerve trunk, is considered. In patients with a complete anatomical break during the operation, an attempt was made to overcome diastasis by measuring the tension force (up to 3 N) with which the nerve was affected. Infrared fluorescence angiography with indocyanine green was performed simultaneously. The obtained angiograms were analyzed, and the effect of the tension force on the change in blood flow in the nerve trunk was determined. It was found that when exposed to a force of up to 2 N, there is no significant change in the intraneural blood flow. At the same time, the effect of a force of 3 N is manifested on angiograms by a significant decrease in the volume of blood flow, which is usually due to constriction of the vessels due to their stretching. After reconstruction (microsurgical epineural suture), repeated angiography was performed to assess the safety and adequacy of blood supply to the nerve. It was revealed that the use of intraopreational angiography with indocyanin green is an affordable and easily feasible technique that allows to determine the safety and, equally important, the adequacy and efficiency of blood flow in the nerve trunk. This technique makes it possible to monitor the safety of blood flow in the nerve trunk, to study the mechanisms of compensation of blood supply to the nerve after microsurgical epineural suture, to assess the quality of comparison of nerve stumps along the axis, excluding the possibility of their "twist".

Cox4i2 Triggers an Increase in Reactive Oxygen Species, Leading to Ferroptosis and Apoptosis in HHV7 Infected Schwann Cells

Emerging evidence suggests that reactive oxygen species (ROS) play a significant role in the pathogenesis of peripheral nerve damage. Our previous study indicated that human herpesvirus 7 (HHV7) induces Bell’s palsy. However, the specific mechanism underlying the effects of ROS in HHV7 infection-induced facial nerve damage is unknown. In this study, we established a rat FN model by inoculating an HHV7 virus solution. The facial grading score and LuxolFastBlue (LFB) staining were used to assess the success of the model. Using mRNA-sequencing analysis, we found that the expression of Complex IV Subunit 4 Isoform 2 (Cox4i2) increased in infected Schwann cells (SCs). Cox4i2 was suggested to increase COX activity, thereby promoting ROS production. The changes in the endogenous oxidant and antioxidant system were assessed, and the results showed that oxidative stress increased after HHV7 infection in vivo and in vitro. However, we found that oxidative injury was relieved after the transfection of shCox4i2 in HHV7-treated SCs by evaluating cell death, cell proliferation, and the ROS level as well as the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Furthermore, we hypothesised that Cox4i2 loss would attenuate HHV7-induced ferroptosis and apoptosis, which are closely related to ROS in SCs. Our research illustrated that the knockdown of Cox4i2 suppresses HHV7-induced RSC96 cell ferroptosis as well as apoptosis via the ERK signalling pathway. Overall, several in vitro and in vivo methods were adopted in this study to reveal the new mechanism of ROS-induced and Cox4i2-mediated apoptosis and ferroptosis in HHV7 infected SCs.