Abstract

OBJECTIVE Several pharmacological treatments have been proposed for the treatment of Complex regional pain syndrome type-I (CRPS-I) in adults, but data regarding the efficacy of various agents for this disease is scarce. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to analyse pharmacological approaches in adults with CRPS-I. METHODS We systematically searched PubMed, Scopus, and Web of Science databases from the inception date to 30, June 2021 for identifying placebo-controlled or active-controlled RCTs using bisphosphonates, ketamine, corticosteroids, anti-epileptics, NSAIDs/COXIBs, opiates, antidepressants, scavengers/magnesium sulphate or intravenous immunoglobulins for the treatment of CRPS-I. The primary outcomes included changes in the visual analogue scale (VAS) or numeric rating scale (NRS) for pain before and after treatment. RESULTS We included 20 placebo-controlled or active-controlled RCTs (for a total of 818 CRPS-I adults) that used bisphosphonates (n = 7), ketamine (n = 2), corticosteroids (n = 2), anti-epileptics (n = 1), NSAIDs/COXIBs (n = 2), scavengers/magnesium (n = 5), or intravenous immunoglobulins (n = 1) to treat CRPS-I during a median follow-up of 26 weeks. The treatment with bisphosphonates showed a significant reduction of the values of the VAS/NRS pain scale compared with placebo or reference therapy (random effects weighted mean difference [WMD]: -23.8, 95%CI-28.0 to -19.6; I2=36.4%). Treatment with ketamine also documented a reduction in the values of the VAS/NRS pain scale (random effects WMD: -8.27,95%CI -12.9 to -3.70; I2=0%). Treatment with other agents did not improve the values of the VAS/NRS pain scale. CONCLUSION This systematic review and meta-analysis supports the recommendation of parenteral bisphosphonates as the first-line agent in the treatment of CRPS-I. REGISTRATION NUMBER Open Science Framework registries; osf.io/et9gu.

Abstract

Pregnancy largely affects disease activity and clinical course in women with immune-mediated neurological disorders. Chronic inflammatory demyelinating polyneuropathy (CIDP) is rare but the most common chronic immune-mediated neuropathy; however, the effects of pregnancy on CIDP have never been investigated except case reports or series. We here provide a systematic review of the literature from 1 January 1969 to 30 June 2020 that revealed 24 women with CIDP, who had onset or relapse during pregnancy. Of these, 17 (71%) developed CIDP during the first pregnancy, and 8 (47%) had a relapse during subsequent pregnancies. Of the 17 patients, in whom the CIDP subtypes were determined, all of them had typical CIDP. First-line treatments for CIDP, such as corticosteroids, immunoglobulin and plasma exchange were efficacious and safe. We suggest that pregnancy can trigger typical CIDP in some women, and women with CIDP have a higher risk of relapse during pregnancy. The onset or relapse of CIDP during pregnancy is a rare but challenging constellation for physicians.

Abstract

Immune checkpoint inhibitors (ICIs) have been increasingly used in the treatment of various types of tumors with favorable results. But these treatments also led to a variety of immune-related adverse events (irAEs). Neurological irAEs such as Guillain-Barré Syndrome are rare and may have serious consequences once they occur. A systematic literature search was performed in PubMed and Embase for all case reports of GBS associated with ICIs published in English reporting on human beings from 1990 up to date. A total of 30 case reports (total patients = 33) were used for final analysis. The included cases were from 11 countries, covering 10 tumor types, with melanoma accounting for the largest number. The mean age was 62.2 ± 11.1 years old, and males were dominant (male: 26 and female: 7). The median time of initial symptoms was 8.2 weeks after the 1(st) dose of ICIs. The most common manifestations of GBS associated with ICIs were weakness, hyporeflexia or areflexia, and paresthesia in order. The GBS subtypes suggested by electrophysiological results were acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and Miller Fisher syndrome (MFS). The protein level of CSF in patients with GBS related to ICIs was 180.68 ± 152.51 mg/dl. Immediate termination of ICIs followed by intravenous immunoglobulin was the preferred treatment option. 72.7% of patients recovered or had residual mild dysfunction after treatment. Elderly male patients with melanoma were most likely to develop ICI-related GBS. The specific neurological symptoms, CSF analysis, and electrophysiological examination were important means of diagnosis.

Abstract

OBJECTIVE To assess effects of treatment against a hypothesized neuroinflammation in children with symptoms corresponding to the research condition Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) which is not included in current diagnostic systems. METHODS Systematic literature searches were performed (1998 to June 2020) in PubMed, Embase, the Cochrane Library, CINAHL, PsycInfo, and HTA databases. Inclusion criteria: patients (P) were children (<18 years) with PANS; intervention (I)/comparison (C) was use of, versus no use of, anti-inflammatory, antibacterial or immunomodulating treatments; outcomes (O) were health-related quality of life (HRQL), level of functioning, symptom change, and complications. RESULTS Four randomised controlled trials (RCTs) and three non-RCTs, including 23 to 98 patients, fulfilled the PICO. HRQL was not investigated in any study. Regarding level of functioning, two RCTs investigated antibiotics (penicillin V, azithromycin) and one RCT investigated immunomodulating treatments (intravenous immunoglobulins (IVIG), plasma exchange). Regarding symptoms, two non-RCTs investigated anti-inflammatory treatment (cyclooxygenase (COX) inhibitors, corticosteroids), two RCTs and one non-RCT investigated antibiotics (penicillin V, azithromycin), and two RCTs investigated immunomodulating treatments (IVIG, plasma exchange). Complications, reported in five studies, were consistent with those listed in the summary of products characteristics (SPC). All studies were assessed to have some or major problems regarding directness, the absence of an established diagnosis contributing to clinical diversity in the studied populations. All studies were assessed to have major risk of bias, including selection and detection biases. Due to clinical and methodological diversity, meta-analyses were not performed. CONCLUSION This systematic review reveals very low certainty of evidence of beneficial effects, and moderate certainty of evidence of adverse effects, of anti-inflammatory, antibacterial or immunomodulating treatments in patients with symptoms corresponding to the research condition PANS. Available evidence neither supports nor excludes potential beneficial effects, but supports that such treatment can result in adverse effects. REGISTRATION PROSPERO (CRD42020155714).

Abstract

BACKGROUND To evaluate the effect of recombinant human erythropoietin (rhEPO) in nervous system of premature infants including different dosage. METHODS The multiple databases like Pubmed, Embase, Cochrane databases and China National Knowledge Database were used to search for the relevant studies, and full-text articles involved in the evaluation on effect of rhEPO for neurodevelopment among premature infants. Review Manager 5.2 was adopted to estimate the effects of the results among selected articles. Forest plots, sensitivity analysis and bias analysis for the articles included were also conducted. RESULTS Finally, 10 eligible studies were eventually satisfied the included criteria. The results showed that rhEPO was much higher than placebo group in composite cognitive score (MD = 5.89, 95% confidential interval {CI} [1.95, 9.82], P = .003; I2 = 89%), there was no significant difference between rhEPO and placebo groups (RR = 0.93, 95% CI [0.60, 1.43], P = .74; I2 = 51%) and no difference in neurodevelopmental impairment between rhEPO and placebo was insignificant (RR = 0.55 95% CI [0.30, 1.02], P = .06). Composite cognitive score in high dose rhEPO was much higher than placebo group (MD = 10.39, 95% CI [8.84, 11.93], P < .0001, I2 = 0%) and low dose rhEPO also had higher composite cognitive score than placebo group (MD = 2.58, 95% CI [0.80, 4.37], P = .004, I2 = 11%). Limited publication bias was observed in this study. CONCLUSION Recombinant human erythropoietin might be a promotor for neurodevelopment among premature infants with limited adverse events.

Abstract

OBJECTIVE The epidemiology and treatment of peripheral neuropathy in systemic sclerosis (SSc) is poorly understood. The objectives of this study were to evaluate the incidence, prevalence, risk factors, and treatments of peripheral neuropathy in SSc. METHODS A systematic review of Medline, Embase and CINAHL databases for literature reporting peripheral neuropathy in SSc was performed. Studies evaluating incidence, prevalence, risk factors, and treatments were synthesized. Meta-analysis using a random effects model was used to evaluate the prevalence of peripheral neuropathy. RESULTS 113 studies reported 949 subjects with at least one type of peripheral neuropathy out of 2143 SSc patients studied. The mean age was 48.5 years. The mean time between SSc onset and detection of peripheral neuropathy was 8.85 years. The pooled prevalence of neuropathy was 27.4% (95%CI 22.4% - 32.7%). Risk factors for peripheral neuropathy in SSc included advanced diffuse disease, anticentromere antibodies, calcinosis cutis, ischemia of the vasa nervosum, iron deficiency anemia, metoclopramide, pembrolizumab, silicosis and uremia. There were 73 subjects with successful treatments (n=36 restoring sensation, n=37 restoring motor or sensorimotor function). Treatments included decompression surgery, prednisone, cyclophosphamide, carbamazepine, transcutaneous electrical nerve stimulation, tricyclic antidepressants and IVIG. CONCLUSION All-cause peripheral neuropathy is not uncommon in SSc. Compression neuropathies can be treated with decompression surgery. Observational data reporting immunosuppressive and anticonvulsants to treat peripheral neuropathy in SSc is limited and conflicting. This data provides the signal of effect to justify RCT to evaluate the efficacy of these interventions.

Abstract

OBJECTIVES To evaluate the efficacy of double-filtration plasmapheresis (DFPP) treatment of myasthenia gravis (MG) through a systematic review and meta-analysis. METHODS PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) on DFPP for MG from database establishment to June 2019. Two researchers independently screened the articles, extracted the data, and cross checked the results. RevMan 5.3 was used for statistical analyses. RESULTS Seven RCTs and 2 CCTs were found comprising 329 patients. The results showed that clinical MG remission rate after DFPP treatment was significantly higher (OR = 4.33; 95% confidence interval [CI], 1.97-9.53; P < .001) and the serum levels of antititin antibody was significantly decreased (standardized mean difference [SMD] = 9.30; 95% CI, 7.51-11.08; P < .001). In addition, the quantitative MG (QMG) score, hospital stay and time to remission of MG symptoms, and acetylcholine receptor antibody (AchRAb) decreased in the DFPP treatment group; however, these outcomes had high heterogeneity among the studies. Only one study has reported on the adverse effects, including hypotension and hematoma. CONCLUSION This meta-analysis suggests that DFPP can be recommended for the short-term mitigation of MG. Because our review was limited by the quantity and quality of the included studies, the above conclusions should be verified by additional high-quality studies.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 2% of children in the United States. Growing evidence suggests that immune dysregulation is associated with ASD. One immunomodulatory treatment that has been studied in ASD is intravenous immunoglobulins (IVIG). This systematic review and meta-analysis examined the studies which assessed immunoglobulin G (IgG) concentrations and the therapeutic use of IVIG for individuals with ASD. Twelve studies that examined IgG levels suggested abnormalities in total IgG and IgG 4 subclass concentrations, with concentrations in these IgGs related to aberrant behavior and social impairments, respectively. Meta-analysis supported possible subsets of children with ASD with low total IgG and elevated IgG 4 subclass but also found significant variability among studies. A total of 27 publications reported treating individuals with ASD using IVIG, including four prospective, controlled studies (one was a double-blind, placebo-controlled study); six prospective, uncontrolled studies; 2 retrospective, controlled studies; and 15 retrospective, uncontrolled studies. In some studies, clinical improvements were observed in communication, irritability, hyperactivity, cognition, attention, social interaction, eye contact, echolalia, speech, response to commands, drowsiness, decreased activity and in some cases, the complete resolution of ASD symptoms. Several studies reported some loss of these improvements when IVIG was stopped. Meta-analysis combining the aberrant behavior checklist outcome from two studies demonstrated that IVIG treatment was significantly associated with improvements in total aberrant behavior and irritability (with large effect sizes), and hyperactivity and social withdrawal (with medium effect sizes). Several studies reported improvements in pro-inflammatory cytokines (including TNF-alpha). Six studies reported improvements in seizures with IVIG (including patients with refractory seizures), with one study reporting a worsening of seizures when IVIG was stopped. Other studies demonstrated improvements in recurrent infections, appetite, weight gain, neuropathy, dysautonomia, and gastrointestinal symptoms. Adverse events were generally limited but included headaches, vomiting, worsening behaviors, anxiety, fever, nausea, fatigue, and rash. Many studies were limited by the lack of standardized objective outcome measures. IVIG is a promising and potentially effective treatment for symptoms in individuals with ASD; further research is needed to provide solid evidence of efficacy and determine the subset of children with ASD who may best respond to this treatment as well as to investigate biomarkers which might help identify responsive candidates.

Abstract

OBJECTIVE To estimate the efficacy of the commonly used long-term immunotherapies in myelin oligodendrocyte glycoprotein IgG associated disorder (MOGAD) METHOD A comprehensive search of the databases including PubMed/MEDLINE, EMBASE, and Cochrane database was performed for all studies that assessed the efficacy of azathioprine (AZA), mycophenolate mofetil (MMF), rituximab (RTX), and maintenance intravenous immunoglobulin (mIVIG) in MOGAD. The random-effect model is used to estimate the standard mean difference (SMD) of annualized relapse rate (ARR) and expanded disability status scale (EDSS), mean ARR, probabilities of relapse and worsening EDSS during treatment. RESULTS The initial search identified 714 articles, and 21 satisfied eligibility criteria. All immunotherapies significantly reduced ARR in both pediatric and adult populations. Relapse probabilities and pooled mean ARR (SE: standard error) during therapies were as follow: AZA 53.1% [95%CI 37.4% to 68.2%; ARR 0.291 (0.134)], MMF 38.5% [95%CI 19.4% to 62.0%; ARR 0.836 (0.176)], RTX 48.9% [95%CI 37.8% to 60.2%; ARR 0.629(0.162)], and mIVIG 25.3% [95%CI 14.0% to 41.3%; ARR 0.081 (0.058)]. Only RTX significantly improved EDSS, SMD -0.499 (95%CI -0.996 to -0.003). The proportion of worsening EDSS with immunotherapies were 20.7% (95%CI 8.8% to 41.6%), 8.1% (95%CI 1.1% to 41.2%), and 10.8% (95%CI 3.8% to 26.8%) for AZA, MMF, and RTX, respectively. CONCLUSION These commonly used immunotherapies significantly reduced ARR in MOGAD. Only RTX had a significant benefit in EDSS improvement. However, a substantial portion of patients continued to relapse with treatment. Randomized controlled studies are needed to verify these findings and perform head-to-head comparisons among these treatment options.

Abstract

OBJECTIVE We examined whether erythropoietin monotherapy improves neurodevelopmental outcomes in near-term and term infants with neonatal encephalopathy (NE) in low-middle income countries (LMICs). METHODS We searched Pubmed, Embase, and Web of Science databases to identify studies that used erythropoietin (1500-12,500 units/kg/dose) or a derivative to treat NE. RESULTS Five studies, with a total of 348 infants in LMICs, were retrieved. However, only three of the five studies met the primary outcome of death or neuro-disability at 18 months of age or later. Erythropoietin reduced the risk of death (during the neonatal period and at follow-up) or neuro-disability at 18 months or later (p < 0.05). Death or neuro-disability occurred in 27.6% of the erythropoietin group and 49.7% of the comparison group (risk ratio 0.56 (95% CI: 0.42-0.75)). CONCLUSION The pooled data suggest that erythropoietin monotherapy may improve outcomes after NE in LMICs where therapeutic hypothermia is not available.