Nerve Function Impairment Research Articles

Exploring the Utility of High-Resolution Ultrasonography and Color Doppler of Peripheral Nerves in Monitoring Response to Treatment in Leprosy Patients: A Prospective, Observational Study.

Diagnosis and monitoring of nerve function impairment (NFI) presents an ongoing challenge in global leprosy control. This was a prospective, observational study in leprosy patients receiving treatment with cutaneous and neurological examinations done every 3 months for 1 year. High-resolution ultrasonography and color Doppler (HRUS-CD) was performed in all patients at baseline, completion of treatment, and anytime during the study period if a patient had deterioration of nerve function noted clinically. All peripheral nerves were assessed, and parameters studied were cross-sectional area (CSA), length of thickening, endoneural flow signals (ENFS), and distortion in fascicular symmetry. Of 54 treatment-naive leprosy patients, loss of sensation was noted in 37 (68.5%), paresthesia in 20 (37.0%), and neuropathic pain in 7 (12.9%) at baseline presentation. At end of treatment of leprosy, maximum improvement in NFI across all clinical criteria was seen in ulnar and radial nerves (P <0.05). The number of impairments on HRUS-CD decreased consistently, significantly for ulnar (P = 0.009 right ulnar, P = 0.012 left ulnar) and right radial (P = 0.025) nerves, and significant improvements in CSA and ENFS were seen across multiple nerves, which correlated with improvement in NFI as well. Abnormal HRUS-CD findings in the target nerves were significantly associated with multibacillary cases (odds ratio [OR]: 4.33; 95% CI: 0.62-30.31), those in reaction (OR: 9.42; 95% CI: 1.51-58.66), and those older than 40 years (OR: 3.14; 95% CI: 0.49-19.93). This study provides objective evidence of improvement in NFI with anti-leprosy treatment, supporting integration of HRUS-CD imaging in monitoring nerve involvement in leprosy.

Correlation of serum zinc and magnesium with reduced heart rate variability in male Parkinson’s disease patients

Background: Parkinson’s disease (PD) is a neurological disorder associated with altered cardiac autonomic function. Heart rate variability (HRV) analysis is a tool to assess the cardiac autonomic status. Altered serum zinc (Zn) and magnesium (Mg) levels are observed in PD. The serum Zn and Mg alteration is associated with nerve function impairment. Objective: To evaluate the relationship between serum zinc, magnesium, and time domain measures of HRV in male patients with PD. Methods: This observational analytical cross-sectional study was conducted in 2023on 30 newly diagnosed male PD patients aged 50-60 years. In this study, 30 healthy volunteers were the control. The 30 patients were divided into different categories based on serum mineral levels. The HRV was recorded by Power Lab 8/35, AD Instruments, Australia and the time domain measures of HRV were used in data analysis. The serum Zn and Mg levels were measured by atomic absorption spectrophotometry. Independent sample ‘t’ test and Pearson’s correlation coefficient test were used for statistical analysis and p&lt;0.05 was considered statistical significance. Results: Significantly higher mean HR (Heart rate) (p&lt;0.01) and significantly lower mean RR (Normal to normal QRS complex) interval,CVRR (Coefficient variation of RR interval) (p&lt;0.01), SDRR (Standard deviation of the RR intervals), SDSD (Standard deviation of the difference between successive RR intervals), RMSSD (Square root of mean squared differences of successive RR intervals), pRR50% (Proportion of RR interval with duration &gt;50 ms) (p&lt;0.001)were observed in PD patients compared to control. In PD patients, significantly lower (p&lt;0.001) serum Zn and significantly higher (p&lt;0.01) serum Mg were observed compared to control. In addition,significant decrement was observed in SDRR, CVRR (p&lt;0.05), SDSD, RMSSD, and pRR50% (p&lt;0.01) in hypozincemic PD patients compared to normozincemic patients. On correlation analysis, significant positive correlations of serum Zn were observed with SDRR (p&lt;0.05),SDSD (p&lt;0.001), RMSSD (p&lt;0.001) and pRR50% (p&lt;0.01). Moreover,serum Mg was positively correlated with SDRR (p&lt;0.05) in PD patients. Conclusion: Hypozincemia and magnesium were directly related to reduced HRV in male PD patients. J Bangladesh Soc Physiol 2023;18(2): 63-71

Effects of Hyperbaric Oxygen Therapy Combined with Music Therapy on Brain Function and Mental Health of Patients with Aneurismal Subarachnoid Hemorrhage: A Retrospective Study.

Hyperbaric oxygen therapy (HBOT), which is widely used in clinical practice, is aimed at improving nerve function impairment after brain injury. Meanwhile, the effects of music therapy on brain function are unclear. This retrospective study was conducted to explore the application effect of HBOT combined with music therapy on patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). For this retrospective study, 130 patients with aSAH after HBOT were selected from our hospital from June 2021 to June 2022. The patients were divided into the observation (n = 70) and control (n = 60) groups based on whether they received music therapy. Comparisons were made on general demographic data, blood flow rate in median cerebral artery (MCA), cerebral vasospasm (CVS), National Institutes of Health Stroke Scale (NIHSS), activities of daily living (ADL) score, Self-Rating Depressive Scale (SDS), and Self-Rating Anxiety Scale (SAS) of patients. Baseline data between the two groups showed no statistically significant difference (P > 0.05). After management, patients in the observation group presented significantly lower SAS and SDS scores (P < 0.05), lower blood flow rate in MCA, CVS and NIHSS scores (P < 0.05), and higher ADL scores than the control group (P < 0.05). The combination of HBOT and music therapy can considerably improve cerebral neurological deficits, slow down cerebral arterial blood flow, promote the recovery of postoperative cerebral function in aSAH patients, and improve anxiety and depression and the patients' ADL.

Changes in the Cutaneous Nerve Fiber Staining and Distribution of PGP9.5 in Clinically Uninvolved Skin in Leprosy Patients after Completion of Multidrug Therapy and Assessing PGP9.5 as a Marker of Treatment Response.

Subclinical involvement of nerves may sometimes be present much before the overt clinical manifestations become apparent. Protein gene product (PGP) 9.5, a ubiquitin-C-terminal hydrolase, has been widely used as a marker to study the involvement of peripheral nerve fibers in many diseases. To evaluate the change in cutaneous nerve fiber staining and distribution from pre-treatment and post completion of multidrug therapy through the expression of PGP9.5 and to assess PGP9.5 as a marker of treatment response. In this prospective single-center observational study, skin biopsy was taken in patients with leprosy, having areas of nerve function impairment (NFI), based on findings of nerve conduction studies (NCSs), but not having lesions or impaired tactile or thermal impairment clinically. The thin nerve fiber density in the clinically normal skin in areas supplied by nerve showing changes of sensory neuropathy was evaluated to study the density of the fibers. A second biopsy was taken at the end of treatment from a site near the previous site to assess the changes in intra-epidermal nerve fiber staining and distribution. Thirty-three patients were recruited in the present study (24 males and 9 females). Pre-treatment, 27 patients had abnormal NCSs, while six patients did not have any evidence of neuropathy on NCSs. Staining for nerve fibers using PGP9.5; in the epidermis was positive in five patients pre-treatment and 11 patients post treatment (P = 0.181). Staining in the dermis revealed positivity in 14 pre-treatment, which increased to 18 post treatment (P = 0.342). Adnexae showed positivity in five patients pre-treatment and increased to 17 post treatment (P = 0.005). A reduced PGP9.5 staining in the epidermal, dermal, and adnexal regions was seen in leprosy patients, which improved post treatment. Thus, PGP9.5 may serve as a marker of NFI and treatment response.

Nerve function impairment and quality of life in patients with leprosy: a prospective, observational study.

There is a limited number of studies assessing the alterations in nerve function impairment (NFI) in leprosy over an extended period of time. To the best of our knowledge, no published study has evaluated neurological state longitudinally during treatment utilizing a combination of clinical, functional (activity limitation), electrophysiological, and patient-reported quality of life (QOL) outcomes. This prospective, observational study included leprosy patients of all spectra. Over 1 year of treatment, cutaneous and neurological examinations were done in addition to a nerve conduction study (NCS) and sympathetic skin response (SSR) assessment. QOL and activity limitation assessments using the World Health Organization Quality of Life brief version (WHOQOL-BREF) and Screening of Activity Limitation and Safety Awareness scale (SALSA), respectively, were also performed. Out of 63 leprosy patients, loss of sensation was noted in 43 (68.2%) at baseline. At the completion of treatment, proportionate change revealed no change in 18 (28.5%), restored function in 9 (14.2%), improved status in 34 (53.9%), and deteriorated NFI in only 2 (3.1%) cases. The association between NCS-SSR abnormalities was significant for a longer duration of disease at presentation (P = 0.04), in multibacillary cases [OR 9.12 (95% CI, 1.22-67.93)], in those in reaction [OR 3.56 (95% CI, 0.62-20.36)] and in those aged over 40 [OR 1.93 (95% CI, 0.28-13.41)]. There was an improvement in WHOQOL-BREF and SALSA scores at release from treatment (P = 0.005 and P = 0.01, respectively). The majority of leprosy patients on treatment show improvement in NFI at the completion of therapy. However, change is influenced by critical factors such as bacillary load, disease duration, age, and the presence of reaction(s).

MIP vaccine in leprosy: A scoping review and future horizons.

Mycobacterium Indicus Pranii (MIP) vaccine is a killed vaccine developed in India for leprosy with immunotherapeutic as well as immunoprophylactic effects. MIP, earlier known as Mycobacterium welchii, is a rapidly growing non-pathogenic mycobacterium. The novelty of this bacterium is due to its translational application as an immunotherapeutic agent. When administered intradermally, the vaccine induces cell-mediated immunity in the host towards Mycobacterium leprae. It leads to faster clinical and histopathological improvement, rapid bacillary clearance, and also lepromin conversion in anergic leprosy patients. The beneficial role of the MIP vaccine in augmenting the therapeutic efficacy of Multidrug Therapy (MDT), particularly in highly bacillated leprosy patients, is well documented in various studies from India. The role of the vaccine in reactional states is controversial, with varied results in different studies. Overall, it is found to decrease the frequency of type 2 lepra reactions and is useful in recalcitrant erythema nodosum leprosum. Even though there may be an increased likelihood of type 1 reactions, no additional nerve function impairment is attributed to the vaccine in various studies. In household contacts of leprosy who are administered MIP, it is noted to confer protection from disease lasting up to 10 years. It may prove to be a cost-effective strategy in national leprosy programmes. Apart from local injection site reactions, the vaccine is relatively safe, but it is not recommended in pregnancy and lactation. This article provides an overview of the MIP vaccine's clinical application in the context of leprosy spanning over 40 years. It also considers the vaccine's possible future applications in the management of disease-related complications and achieving the long-term goal of zero leprosy.

Dosimetric comparison of helical tomotherapy and volumetric modulated arc therapy in hippocampal avoidance whole-brain radiotherapy.

This study aimed to discuss the dosimetric advantages of helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) technology in hippocampal avoidance whole-brain radiotherapy and provide references for clinical selection of ideal radiotherapy technology. A total of 20 patients with hippocampal avoidance whole-brain radiotherapy were chosen randomly. Computed tomography (CT) and MRI scanning images were input into the treatment planning system (TPS). After the CT and enhanced magnetic resonance T1 weighted images were fused and registered, the same radiation therapy physician was invited to outline the tumor target volume. PTV-HS refers to the whole brain subtracted by 5mm outward expansion of the hippocampus (HP). The prescribed dose was 30Gy/10 fractions. HT and VMAT plans were designed for each patient in accordance with PTV. Under the premise that the 95% isodose curve covers the PTV, dose-volume histogram was applied to evaluate the PTV, conformal index (CI), heterogeneity index (HI), maximum dose (Dmax), mean dose (Dmean), minimum dose (Dmin) and absorbed doses of organs at risk (OARs) in HT and VMAT plans. Paired t-test was performed to compare the differences between two radiation therapy plans, and p < 0.05 was considered statistically significant. These two plans had no significant difference in PTV-HS (max, min, and mean). However, the HI and CI of the HT plan were significantly better than those of the VMAT plan, showing statistically significant difference (p<0.05). The HT plan was significantly superior to the VMAT plan in terms of the Dmax, Dmin, and Dmean of HP, left and right eye lens, left and right eye, and spinal cord, showing statistically significant difference (p<0.05). The HT plan was also better than the VMAT plan in terms of the Dmax of the left optic nerve. However, the two plans showed no obvious differences in terms of the absorbed doses of the right optic nerve and brainstem, without statistical significance. Compared with the VMAT plan of hippocampal avoidance, HT technology has significant dosimetric advantages. HT plans significantly decreased the radiation dose and radiation volume of OARs surrounding the target area (e.g., surrounding eye lens and eye, especially hippocampal avoidance area) while increasing the CI and HI of PTV dose in whole brain radiotherapy (WBRT) greatly, thus enabling the decrease in the incidence rate of radioactive nerve function impairment.

Immunopathogenesis of Type 1 and Type 2 Leprosy Reaction: An Update Review.

Leprosy reactions are acute exacerbations of the signs and symptoms of leprosy occurring during the natural course of the disease and during or after treatment. Left untreated or improperly managed, reactions can lead to severe nerve function impairment and subsequently to disabilities. In the present context of leprosy eradication efforts, leprosy reactions continue to pose a significant and enduring challenge. Type 1 leprosy reactionand type 2 leprosy reaction are substantial contributors to nerve impairment and the subsequent development of enduring impairments. The study ofimmunopathogenesis of leprosy reactions has emerged as a significant area of research due to its potential to identify critical targets for the early detection and management of these episodes. This study aims to reveal the pathogenesis of type 1 and 2 leprosy reactions so that they can form the basis for their treatment. The study used scientific journals from reputable platforms such as PubMed, Scopus, and Google Scholar to evaluate the pathogenesis of leprosy reaction type 1 and 2 in leprosy patients. This review indicates that the progression of leprosy nerve damage and sensitivity to reactions may be predicted using genetic and serum markers in the human host. A more profound comprehension of the molecular processes underlying leprosy reactions may offer a logical plan for early detection and leprosy reaction complication prevention.

COVID-19 vaccination and leprosy-A UK hospital-based retrospective cohort study.

Individuals with leprosy are at risk of leprosy reactions, T-cell mediated immunological complications, which lead to nerve function impairment. Leprosy reactions require systemic immunosuppression which is a risk factor for severe COVID-19. Vaccination for SARS-CoV-2 infection is recommended in the UK and became widely available in 2021 with individuals at increased risk of severe disease, including the immunosuppressed, prioritised. Vaccines for SARS-CoV-2 may provoke a T cell response. The latter poses a theoretical risk of provoking an immunological response to latent Mycobacterium leprae infection leading to clinical disease or in those with clinical disease triggering a leprosy reaction. BCG vaccination is associated with the development of leprosy in a small proportion of healthy contacts of people with leprosy within twelve weeks of administration. BCG causes a Th1 immune response. We performed a retrospective cohort study to determine the SARS-CoV-2 vaccination status of individuals diagnosed with leprosy attending the Leprosy Clinic in 2021 and whether any had developed leprosy or experienced a new leprosy reaction within twelve weeks of receiving a dose of a SARS-CoV-2 vaccine. The electronic patient records were used to retrieve data. Fifty-two individuals with leprosy attended the clinic in 2021 of which five people were newly diagnosed with leprosy. Thirty-seven (71%) were male and the median age was 48.5 years old (Range 27-85 years). Eight (15.4%) individuals were taking multi-drug therapy (MDT) and eight (15.4%) had completed MDT within three years of the study. Twenty-two (41.5%) individuals were prescribed a systemic immunosuppressant drug during 2021. Ten (18.9%) individuals have one or more risk factors for severe COVID-19. The SARS-CoV-2 vaccination status of fifty (96%) were recorded of which forty-nine were vaccinated (98%). One individual had declined vaccination. One individual was diagnosed with borderline tuberculoid (BT) leprosy having developed red skin lesions with reduced sensation (which increased in size and number) and thickened peripheral nerves one week after a second dose of BNT162b2 vaccine. Another individual who had completed MDT more than three years earlier developed red plaques and tender thickened nerves consistent with a leprosy Type 1 reaction eight weeks after a single dose of BNT162b2 vaccine (having received two doses of CoronaVac vaccine three months earlier). The development of BT leprosy and a Type 1 reaction in another individual shortly after a dose of BNT162b2 vaccine may be associated with vaccine mediated T cell responses. The benefits of vaccination to reduce the risk of severe COVID-19 outweigh these unwanted events but data from leprosy endemic countries may provide further information about potential adverse effects of augmented T cell responses in individuals with leprosy or latent M. leprae infection.

The potential of MLC901 as adjuvant therapy for traumatic spinal cord injury by multi-pathway biomechanism: a systematic review

Background: Traumatic spinal cord injury (tSCI) is a severe neurological condition that causes long-term nerve function impairment and can even cause death. Further efforts are needed to find better therapy for this condition to improve patients' quality and life expectancy. Moleac 901 (MLC901) is a phytopharmacological refinement that incorporates important molecules to facilitate progenitor nerve cell amplification and differentiation and has significant neuroprotective effects in tSCI cases. This systematic review aims to discover the potential of MLC901 as adjuvant therapy for traumatic spinal cord injury by multi-pathway biomechanism. Methods: Researchers searched for data sources using three databases (PubMed, Science Direct, and Google Scholar) using the keywords “MLC901” and “Spinal Cord Injury.” Articles are included if related to the potential and biomechanism of MLC901 and/or its constituent components in tSCI therapy, using RCT designs, observational, animal studies, and/or original research, including national and international articles from 2013-2023. Article selection followed PRISMA's guidelines for measuring the quality of systematic reviews. Results: Total of 123 articles were obtained from the database search, and then 13 articles were identified that met the review requirements. Of the 13 articles reviewed, two were related to MLC901 therapy in tSCI: one animal study article and one cohort study in humans. In contrast, the other 11 articles are animal and pharmacological analysis studies discussing the benefits of MLC901 components for tSCI therapy. The MLC901's active ingredients, such as paeoniflorin, safflower yellow, salvianolic acid B, and astragali radix-angelicae sinensis radix, have demonstrated their potential in targeting multiple pathways involved to prevent inflammation, improve microcirculation, protect damaged nerve cells, and promote nerve repair and regeneration. Conclusion: MLC901 acts primarily as an adjuvant treatment for spinal cord injury by promoting a neuroprotective effect, inhibiting apoptosis, stimulating neurite growth, and reducing pro-inflammatory cytokines.

Comparison between lymecycline with multidrug therapy and standard multidrug regimen (WHO-MDT) in the treatment of multibacillary leprosy patients: a retrospective cohort study.

Hansen's disease or leprosy is a chronic, infectious disease that has locally and globally afflicted all populations. Despite standard treatment with multidrug therapy (WHO-MDT), the incidence of drug resistance has been an increasingly prevalent global problem in leprosy management. This study compared the effectiveness between lymecycline with WHO-MDT and standard WHO-MDT in leprosy treatment. The research is a retrospective cohort study at a tertiary hospital from January 2011 to July 2021. Pre- and post-treatment bacillary index, presence of new lesions, nerve function impairment, and leprosy reactions were obtained through chart review. The results showed a significant difference in bacteriological index (BI) in both groups at the end of the treatment. However, a higher reduction in BI was noted for the lymecycline group. For the group that took WHO-MDT alone, BI decreased by 0.7 (P < 0.001) whereas patients who took lymecycline and WHO-MDT had a BI difference of 3 (P < 0.001) upon completion of treatment. A significant decrease in the recurrence of lesions (P = 0.006) and nerve function impairment (P = 0.038) was also noted in the lymecycline group whereas there was no significant difference in leprosy reactions between the two groups. Lymecycline 600 mg daily for 3 months can be used as an adjunct in cases of leprosy resistance and treatment failure among multibacillary patients. Lymecycline significantly reduced bacillary index, recurrence of skin lesions, and nerve function impairment through its possible immunomodulatory, antiapoptotic, and neuroprotective effects.

An experimental model of peripheral nerve electrical injury in rats

IntroductionAlthough several studies have investigated models of nerve electrical injury, only a few have focused on electrical injury to peripheral nerves, which is a common and intractable problem in clinical practice. Here, we describe an experimental rat model of peripheral nerve electrical injury and its assessment. MethodsA total of 120 animals were subjected to short-term corrective electrostimulation (50 Hz, 1-s duration) applied at varying voltages (control, 65, 75, 100, 125, and 150 V) to the exposed left sciatic nerve. Behavioural testing, electrophysiological measurements, and histopathological observation of the sciatic nerve were conducted at 1-, 2-, 4-, and 8-w follow-ups. ResultsNo functional defects were noted in the groups that received 65-V stimulation at any time point. Sciatic nerve functional defects were found after 2 w in animals that received 75-V stimulation, but function returned to normal after 4 w. In animals that received 100-V and 125-V stimulation, functional defects were observed at 4 w, but had partially recovered by 8 w. Conversely, animals that received 150-V stimulation did not show recovery after 8 w. ConclusionWe presented a model of peripheral nerve electrical injury that avoided the interference of various external factors, such as current instability, compression of the surrounding tissues, and altered blood supply. The model allowed quantitation and ranking of the nerve injury into four degrees. It facilitated effective evaluation of nerve function impairment and repair after injury. It can be used post-surgically to evaluate peripheral nerve impairment and reconstruction and enables translational interpretation of results, which may improve understanding of the mechanisms underlying the progression of peripheral nerve electrical injury.

Systematic Review of Survival Analysis in Leprosy Studies-Including the Following Outcomes: Relapse, Impairment of Nerve Function, Reactions and Physical Disability.

Leprosy is a public health problem in South American, African and Oceanian countries. National programs need to be evaluated, and the survival analysis model can aid in the construction of new indicators. The aim of this study was to assess the period of time until the outcomes of interest for patients with or exposed to leprosy by means of survival analysis surveys. This review researched articles using the databases of PubMed, Science Direct, Scopus, Scielo and BVS published in English and Portuguese. Twenty-eight articles from Brazil, India, Bangladesh, the Philippines and Indonesia were included. The Kaplan–Meier method, which derives the log-rank test, and Cox’s proportional hazards regression, which obtains the hazard ratio, were applied. The mean follow-up until the following outcomes were: (I) leprosy (2.3 years) in the population who were exposed to it, (II) relapse (5.9 years), (III) clinical manifestations before, during and after treatment—nerve function impairment (5.2 years), leprosy reactions (4.9 years) and physical disability (8.3 years) in the population of patients with leprosy. Therefore, the use of survival analysis will enable the evaluation of national leprosy programs and assist in the decision-making process to face public health problems.

Early detection of sensory nerve function impairment in leprosy under field conditions.

To assess the fine sensation of palms and soles in field conditions, to enable early detection of nerve function impairment before the loss of protective sensation, thus preventing the development of disability. A cross-sectional descriptive study was conducted at seven tertiary referral hospitals located in different states in India. This study included all newly diagnosed patients affected by leprosy, who were registered during the period between March 2011 and April 2012. A detailed history was taken along with charting and voluntary muscle testing /sensory testing (VMT/ST) for the diagnosed patients. The sensation was measured using 0.2 gm Semmes-Weinstein filaments for palms and 4 gm for soles first, followed by 2 gm Semmes-Weinstein filaments for palms and 10 gm for soles. Among the 374 patients, 106 were identified with sensory nerve function impairment. Of the 106 patients, 84 were identified with absence of both fine and protective sensation and 22 patients had a loss of fine touch sensation with protective sensation intact. This study was conducted only among patients who were newly diagnosed with leprosy. Hence, future longitudinal studies in a larger population will add more validity to the study. The patients who had loss of fine sensation would have been missed by the normal leprosy programme protocol which uses 2 gm and 10 gm filaments for testing sensory loss before initiating steroid therapy. Further research is needed to determine whether testing for fine sensation with 0.2 gm Semmes-Weinstein filaments for palms and 4 gm for soles can be introduced at all specialized leprosy centres to detect nerve function impairment at an earlier stage followed by steroid therapy.

Mid-Borderline Leprosy with Mild Type 1 Reaction in Children: A Case Report

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Cases of leprosy in children are rarely found because of the long incubation period of Mycobacterium leprae. Purpose: To report a case of mid-borderline leprosy with a mild type 1 reaction in a seven-years-old girl patient. Case: A 7-years-old girl patient presented with multiple red and white patches on her face, body, arms, legs, and buttocks since 6 months before. There was no itching, numbness, painr fever. There was no thickening of peripheral nerves and no nerve function impairment. Her grandmother was suspected to have leprosy, but she had never been treated and had already passed away. From the acid fast bacilli (AFB) examination, the bacterial index (BI) was 1+ and the morphological index (MI) was 2%. A serologic test examination was also performed and the result were Immunoglobulin (Ig) G 3716 u/ml and IgG 284 u/ml. The patient got multidrugs therapy for 12 months and after 9 months of treatment, the pre-existing patches became erythematous, thickened, and felt pain when touched, but there was no fever. In the presence of pain, oral ibuprofen was then administered and the patches began to improveDiscussion: Due to the possibility of leprosy reaction, it is important to immediately give prompt treatment to children with type 1 leprosy reaction that is associated with neuritis and leads to deformities. Conclusion: Early diagnosis and therapy for a type 1 leprosy reaction are very important to prevent deformities.

The Armadillo as a Model for Leprosy Nerve Function Impairment: Preventative and Therapeutic Interventions.

Mycobacterium leprae infection of peripheral nerves and the subsequent nerve function impairment (NFI), especially in response to reactional episodes, are hallmarks of leprosy. Improved treatments for M. leprae-induced nerve injury are needed, as most if not all of the disability and stigma associated with leprosy arises from the direct or indirect effects of NFI. Nine-banded armadillos (Dasypus novemcinctus), like humans, exhibit the full clinical spectrum of leprosy and extensive involvement of the peripheral nerves. In this study, state-of-the-art technology was used to compare nerve function between uninfected and M. leprae-infected armadillos. Motor nerve conduction velocity (MNCV) and compound muscle action potential (cMAP), which measure changes in the rate of impulse conduction velocity and amplitude, revealed a progression of impairment that was directly correlated with the duration of M. leprae infection and enabled development of an objective nerve impairment scoring system. Ultrasonography accompanied by color Doppler imaging detected enlargement of the M. leprae-infected nerves and increased vascularity, possibly due to inflammation. Assessment of epidermal nerve fiber density (ENFD), which shows a length-dependent innervation in armadillos that is similar to humans, identified small fiber degeneration early after M. leprae infection. Staining for neuromuscular junction (NMJ) integrity, which is an indicator of signal transduction efficiency into skeletal muscle, discerned a markedly lower number and structural integrity of NMJ in M. leprae-infected armadillo footpads. These tools for assessing nerve injury were used to monitor the effects of intervention therapy. Two potential neuro-protective drugs, ethoxyquin (EQ) and 4-aminopyridine (4-AP), were tested for their ability to ameliorate peripheral nerve injury in M. leprae-infected armadillos. 4-AP treatment improved MNCV, cMAP, and EFND compared to untreated animals, while EQ had less effect. These results support the armadillo as a model for M. leprae-induced peripheral nerve injury that can provide insights toward the understanding of NFI progression and contribute to the preclinical investigation of the safety and efficacy of neuro-preventive and neuro-therapeutic interventions for leprosy.

Effectiveness of Combined Thrombolysis and Mild Hypothermia Therapy in Acute Cerebral Infarction: A Meta-Analysis

Objective To evaluate the effectiveness and safety of thrombolytic therapy combined with mild hypothermia in patients with acute cerebral infarction (ACI), based on a meta-analysis of randomized controlled trials (RCTs). Methods PubMed, EMBASE, Cochrane Library, and Chinese National Knowledge Infrastructure Database of Controlled Trials were systematically screened for randomized controlled trials (RCTs) of thrombolytic therapy combined with mild hypothermia in treating ACI from inception to January 2021. Participation and outcomes among intervention enrollees are as follows: P, participants (patients in ACI); I, interventions (thrombolysis in combination with mild hypothermia therapy); C, controls (thrombolysis merely); O, outcomes (main outcomes are the change of NIHSS, glutathione peroxidase, superoxide dismutase, malondialdehyde, inflammatory factor interleukin-1β, tumor necrosis factor-α, and adverse reaction). Following data extraction and quality assessment, a meta-analysis was performed using RevMan 5.3 software. Results A total of 26 RCTs involving 2071 patients were included. Compared to thrombolysis alone, thrombolytic therapy combined with mild hypothermia leads to better therapeutic efficacy [RR = 1.23, 95% CI (1.16, 1.31)], NIHSS [MD = −2.02, 95% CI (−2.55, −1.49)], glutathione peroxidase [MD = 8.71, 95% CI (5.55, 11.87)], superoxide dismutase [MD = 16.52, 95% CI (12.31, 19.74)], malondialdehyde [MD = −1.86, 95% CI (−1.98, −1.75)], interleukin-1β [MD = −3.48, 95% CI (−4.88, −2.08)], tumor necrosis factor-α [MD = −0.46, 95% CI (−3.39, 2.48)], and adverse reaction [RR = 0.87, 95% CI (0.63, 1.20)]. Conclusions Thrombolytic therapy combined with mild hypothermia demonstrates a beneficial role in reducing brain nerve function impairment and inflammatory reactions in ACI subjects analysed in this meta-analysis.

Leprosy Reactions and Neuropathic Pain in Pure Neural Leprosy in a Reference Center in Rio de Janeiro - Brazil.

IntroductionLeprosy reactions are complications that can occur before, during, or after multidrug therapy (MDT) and are considered a major cause of nerve damage. Neuritis is an inflammatory process that causes nerve function impairment associated with pain and tenderness along the nerve. Neuritis can be found in both type 1 and type 2 reactions and may also be the sole manifestation of a leprosy reaction. The objective of this study is to describe the incidence of leprosy reactions and its association with neuropathic pain in pure neural leprosy (PNL) patients.MethodsWe selected 52 patients diagnosed with PNL and 67 patients with other clinical forms of leprosy. During the MDT the patients visited the clinic monthly to take their supervised dose. The patients were instructed to return immediately if any new neurological deficit or skin lesions occurred during or after the MDT.ResultsOf the PNL patients, 23.1% had a leprosy reaction during or after the MDT, while this was 59.7% for patients with the other clinical forms of leprosy. There was an association between having PNL and not having any reaction during and after the MDT, as well as having PNL and having neuritis after the MDT.There was also an association between having previous neuritis and having neuropathic pain in the other clinical forms of leprosy group, although this association was not present in the PNL group.DiscussionOur data suggest that PNL is a different form of the disease, which is immunologically more stable. In addition, PNL patients have more neuritis than the classical leprosy skin reactions. In PNL there was no association between acute neuritis and neuropathic pain, suggesting that these patients may have had silent neuritis. Understanding and identifying neuritis is essential to reduce disability and the impact on public health.

Exosomes Secreted by Hypoxia-Pre-conditioned Adipose-Derived Mesenchymal Stem Cells Reduce Neuronal Apoptosis in Rats with Spinal Cord Injury.

Neuronal death is the main cause of nerve function impairment after spinal cord injury (SCI). Exosome-based therapy has become a novel strategy for tissue injury repair. We designed a method to treat SCI using exosomes secreted by adipose tissue-derived stromal cells (ADSCs) under hypoxic conditions. We established a neuronal oxygen-glucose deprivation and reperfusion (OGD/R) model in vitro to simulate the hypoxic environment after SCI. We observed that exosomes derived from hypoxia-conditioned ADSCs (Hypo-exo) significantly reduced neuronal apoptosis after OGD. By establishing a rat SCI model, we found that Hypo-exo can significantly reduce the formation of cavities in the injured area and improve the functional recovery of the hindlimbs of rats after injury. To explore the molecular mechanism, we conducted microRNA sequencing analysis of exosomes. Through real-time polymerase chain reaction, dual luciferase reporter assays and signaling pathway chip analysis, we determined that miR-499a-5p regulates the JNK3/c-jun-apoptotic signaling pathway by targeting JNK3. Further, we verified the expression of the key proteins in the JNK3/c-jun-apoptotic signaling pathway by immunofluorescence and Western blotting. These results support the hypothesis that Hypo-exo can reduce neuronal apoptosis after SCI and may provide new methods to treat SCI.

Skin Advanced Glycation End Products among Subjects with Type 2 Diabetes Mellitus with or without Distal Sensorimotor Polyneuropathy

Materials and Methods We included 132 subjects (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm. The device enables single and automated triplicate measurements: both of these were performed. DSPN was diagnosed through the neuropathy disability score (NDS). Small nerve fibre function was assessed by temperature and pinprick sensation on the foot. Bilateral measurement of the vibration perception threshold (VPT) on the hallux was carried out by using a neurothesiometer (Horwell Scientific Laboratory Supplies). Results Single and triplicate AGE measurements were positively correlated with each other (Pearson's correlation coefficient r = 0.991, 95%CI = 0.987-0.994, p < 0.001). AGEs were higher among subjects with vs. those without DSPN (p < 0.001). Furthermore, they were higher among subjects with reduced vs. normal temperature sensation (p < 0.001), among subjects with reduced vs. normal pinprick sensation (p = 0.002), among those with abnormal vs. normal monofilament examination (p < 0.001), and among those with abnormal vs. normal VPT (p < 0.001). AGEs were correlated with NDS, VPT, and monofilament score. Conclusions In T2DM, skin AGEs are increased in the presence of DSPN. This holds true both for large and for small nerve function impairment. Moreover, AGEs are correlated with DSPN severity.