Chronic Neuropathy Research Articles

Late side effects of testicular cancer and treatment: a comprehensive review.

Testicular cancer is a rare solid organ tumour associated with high cure rates and young age at diagnosis, hence it has a sizeable cohort of survivors worldwide. As it is one of the earliest tumours to be cured, a lot of studies have highlighted the late side effects of cancer and its different treatment modalities including surgery, radiotherapy and chemotherapy. While we are trying to identify the population at higher risk of platinum based chemotherapy and reduce its exposure, cisplatin based regimes remain an important tool to cure testicular cancer. The list of late side effects include a number of fatal and morbid conditions including but not limited to the second malignant neoplasms, cardiovascular disease, hypogonadism, infertility, metabolic syndrome, chronic respiratory disease, renal insufficiency, hearing loss, peripheral neuropathy, infertility and psychological illnesses like stress and anxiety. These complications eventually result in compromised social and economic health as well as lower life expectancy compared to the normal population. This article provides a comprehensive review of the latest data regarding the late side effects in testicular cancer survivors. A review of these conditions can help us develop recommendations and guidelines to improve the morbidity and mortality in survivors of testicular cancer.

Genetic Insights and Epidemiological Models in Understanding Primary Open Angle Glaucoma

Primary open-angle glaucoma (POAG) is a multifactorial chronic optic neuropathy with significant genetic heterogeneity. The pathogenesis of POAG involves an imbalance between the production and drainage of aqueous humor (AH). Genetic theories suggest that transgenic mice demonstrating the GLU50LYS mutation in optineurin (OPTN) experience retinal ganglion cell apoptosis, while mutant myocilin (MYOC) proteins induce endoplasmic reticulum (ER) stress, leading to an unfolded protein response (UPR) and subsequent apoptosis of trabecular meshwork cells (TMC). Furthermore, the interaction between MYOC and mitochondria in the trabecular meshwork (TM) and astrocytes may lead to mitochondrial membrane depolarization and calcium channel dysregulation, contributing to POAG. Overexpression of MYOC variants (P370L, Q368X) is also implicated, as are epigenetic modifications and signaling pathways such as histone and DNA modification. POAG has been associated with autosomal dominant inheritance, with mutations in MYOC and OPTN being prominent causative factors, although many cases involve multiple genetic loci. Currently, over 20 genetic loci have been linked to POAG, with 14 chromosomal loci (GLC1A to GLC1N) identified, 5 of which contribute to juvenile-onset open-angle glaucoma (JOAG). Of these loci, MYOC, OPTN, WD repeat domain 36 (WDR36), and neurotrophin-4 (NTF4) are the most studied causative genes. The ongoing study of molecular genetics offers potential pathways for future therapeutic advances in the treatment of POAG.

Retraction: Potamogeton perfoliatus L. extract attenuates neuroinflammation and neuropathic pain in sciatic nerve chronic constriction injury-induced peripheral neuropathy in rats.

[This retracts the article DOI: 10.3389/fphar.2021.799444.].

Observing nociceptive detection thresholds and evoked potentials in diabetic patients with and without painful neuropathy

Aim: Diabetic polyneuropathy is the most described complication in patients with diabetes mellitus. A significant percentage of these patients experience disabling neuropathic pain (painful diabetic polyneuropathy). Small nerve fibers are primarily responsible for peripheral nociception, but objectively assessing its function is challenging. The primary objective of this study was to explore the task execution and outcomes of intra-epidermal electrical stimulation technique that combines nociceptive detection thresholds (NDT) and evoked potentials (EPs) in patients with diabetes. We compared the results of diabetic patients, both with and without painful diabetic polyneuropathy, with those of healthy controls to explore potential clinically relevant information. Methods: The NDT-EP method was applied to 38 patients with diabetes (18 with and 20 without chronic painful neuropathy) and 38 age- and sex-matched healthy controls. Individual mean NDTs, psychometric slopes, EP amplitudes, and the effect of the stimuli on EP amplitudes were analyzed and compared between groups using linear regression. Results: The findings revealed significantly lower detection rates, higher NDTs, and lower psychometric slopes in patients with painful diabetic polyneuropathy than in healthy controls. Both patient groups significantly exhibited lower mean EP amplitudes than healthy controls, which were not linked to pulse amplitudes but influenced by stimulus detection. Conclusions: This study showed altered NDT-EP outcomes in patients with painful diabetic polyneuropathy. Whereas the task execution, NDTs, and psychometric slopes may provide valuable insights into small fiber dysfunction, pulse amplitudes seemed not differently encoded in neurophysiological responses to intra-epidermal electrical stimulation near the detection threshold compared to controls. Future studies should investigate whether the altered NDT-EP outcomes could quantify small fiber dysfunction in patients with diabetes mellitus. We recommend further exploration of NDT-EP measures in other patient groups with nociceptive dysfunction.

Acupuncture as Adjuvant Therapy for Glaucoma: Protocol for a Randomized Controlled Trial.

Glaucoma is a chronic progressive optic neuropathy that necessitates lifelong treatment to reduce the decline of the optic nerve. Due to the extended and continuous treatments required for patients, complementary therapies are often considered alongside conventional treatments to enhance the effectiveness of the treatment. Acupuncture has demonstrated the potential to lower intraocular pressure in previous clinical trials, making it a promising glaucoma intervention. The primary objective of this study is to conduct a single-center randomized control trial involving patients with glaucoma. Acupuncture will be evaluated as an adjunctive therapy. The trial aims to explore its effectiveness for glaucoma. In this single-center randomized controlled trial, participants (N=50) with primary open-angle glaucoma will be randomly assigned to the treatment group, receiving ophthalmic acupuncture with "De Qi" sensation, or the control group, receiving minimum acupuncture stimulation on nonophthalmic acupoints. The intervention will consist of weekly acupuncture treatments for a total of 6 sessions. Participants will be assessed at 8 time points, which are baseline, during the intervention (6 times), and at a 3-month follow-up. The primary outcome measure is a change in the intraocular pressure before and after each acupuncture treatment. Secondary outcomes will include measurements of heart rate and blood pressure before and after acupuncture, best-corrected visual acuity, visual field, optical coherence tomography, optical coherence tomography angiography, the Glaucoma Symptom Scale, and the Glaucoma Quality of Life-15 questionnaire. Recruitment of participants for the trial commenced on June 28, 2023. A total of 10 participants have been enrolled to test the feasibility of the experiment. We anticipate that the preliminary data from this trial will be completed by December 2025. This trial uses rigorous methodology and comprehensive outcome measurements to assess the clinical efficacy of acupuncture as an adjunctive therapy for glaucoma, providing valuable insights for future clinical treatment guidelines. ClinicalTrials.gov NCT05753137; https://clinicaltrials.gov/study/NCT05753137. DERR1-10.2196/57888.

The single-cell transcriptomic atlas iPain identifies senescence of nociceptors as a therapeutical target for chronic pain treatment

Chronic pain remains a significant medical challenge with complex underlying mechanisms, and an urgent need for new treatments. Our research built and utilized the iPain single-cell atlas to study chronic pain progression in dorsal root and trigeminal ganglia. We discovered that senescence of a small subset of pain-sensing neurons may be a driver of chronic pain. This mechanism was observed in animal models after nerve injury and in human patients diagnosed with chronic pain or diabetic painful neuropathy. Notably, treatment with senolytics, drugs that remove senescent cells, reversed pain symptoms in mice post-injury. These findings highlight the role of cellular senescence in chronic pain development, demonstrate the therapeutic potential of senolytic treatments, and underscore the value of the iPain atlas for future pain research.

Applicability of QbD-assisted Analytical Method for Simultaneous Detection of Tetrahydrocurcumin and Folic Acid in Developed Nanostructured Lipid Carriers

Aims: Applicability of QbD-assisted analytical method for simultaneous detection of tetrahydrocurcumin and folic acid in developed nanostructured. Background: Diabetic foot ulcer (DFU) is a multifactorial disorder that involves chronic inflammation, oxidative stress and neuropathy. Current treatment therapies involving the use of growth factors and skin substitutes being costly, are out of reach for the majority of patients. The present research explored the usefulness of (5929IN008, application number 202211045937), a combination of tetrahydrocurcumin and folic acid-loaded nanostructured lipidic carriers. Objectives: To develop and validate a QbD-assisted method for simultaneous analysis of tetrahydrocurcumin (THC) and folic acid (FA). Applicability of the above method to determine total drug content (TDC) and entrapment efficiency (EE) of nanostructured lipid carriers (NLCs) loaded THC and FA. Methods: A high-performance liquid chromatographic (HPLC) method was developed, optimized and validated using Box-Behnken design for improved method performance. Chromatographic separation was conducted on a Supelco 250 x 4.6 mm (5 μm) column with optimized mobile phase composition containing tetrahydrofuran: citric acid buffer pH 3.5 (50:50) at a flow rate of 0.4 mL.min-1 and diode array detection between 210 and 360 nm. Results: The method developed in a concentration range of 1 to 100 μg.mL-1 was found to be linear (R2 0.999, p≤0.001), accurate (99.10-101.70%) and precise with high recovery values in intra and inter-day results. The system adaptability and robustness evaluation revealed that the percent recovery ranged from 96.90 to 102.80%, and the percent relative standard deviation (%RSD) values were less than 2%. Moreover, the method was further applied for the determination of TDC (86±6% and 96±8%) and drug EE (81±21% and 73±13%) for THC and FA, respectively. Conclusion: The investigation indicated the applicability of the developed and validated method for the estimation of THC and FA in the developed nanostructured lipidic carriers.

Correlation Between Orofacial Pain and Sensory and Autonomic Neuropathies.

Orofacial Pain (OFP) affects 15% of the general population. OFP conditions can be myofascial, also known as temporomandibular disorders (TMDs) or neuropathic. The underlying pathophysiology in several chronic OFP conditions, is unknown. Small fiber neuropathy (SFN) is a disorder of thinly myelinated A-delta and non-myelinated C-fibers and can manifest as sensory and autonomic neuropathies. SFN has been demonstrated in some OFP conditions. Our study aims to assess the presence of OFP in patients with sensory and autonomic neuropathies and assess the correlation between OFP, skin biopsy and autonomic dysfunction. This is a retrospective study (2018-2020) of patients from the SFN registry, Massachusetts General Hospital, Boston, USA, for the presence of OFP. All patients were included. Primary outcome: Prevalence of OFP in patients with chronic neuropathies. Secondary outcomes: Correlation between OFP and skin biopsy, dysautonomia, headaches, chronic nociceptive pain, psychological conditions, and patient factors, such as mean age and BMI. Charts of 450 patients with sensory and autonomic neuropathies were reviewed. 22.67% (n=102) had OFP. The mean (range) age at biopsy in patients with OFP was 48.36 (20-81) years, female: male ratio 3.25:1. More OFP patients had negative skin biopsy results (p value<0.05) than those with sensory neuropathies. Patients with OFP had significantly higher prevalence of psychological conditions (p value 0.000), and higher BMI >30 (p value 0.025). Dysautonomia was significantly higher in patients with TMDs when compared to the ones without TMDs (p value 0.030). There was no significant difference in mean age, gender predilection, presence of headaches, peripheral neuropathies, and nociceptive pain between patients with and without OFP. OFP and sensory neuropathies can be overlapping conditions. Patients presenting with concomitant TMD and dysautonomia can be further tested for SFN. This can further help us understand a correlation if any, between idiopathic TMD/OFP conditions and SFN and further our understanding of the pathophysiology of these conditions.

ID: 330248 High Cervical Spinal Cord Stimulation for the Treatment of Chronic Postoperative Painful Trigeminal Neuropathy

ID: 330248 High Cervical Spinal Cord Stimulation for the Treatment of Chronic Postoperative Painful Trigeminal Neuropathy

Medical Cannabis Dosing Trajectories of Patients: Evidence From Sales Data

Medical cannabis use is rising with limited high-quality clinical trial data to guide dosing. This study relies on real-world, longitudinal medical cannabis purchase data to provide information on Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) dosing trends for patients with qualifying medical conditions. A retrospective study of purchases by 16,727 patients obtaining medical cannabis from dispensaries located in New York between 2016 and 2019, recorded in point-of-sale data. Group-based trajectory modeling was used to identify clusters of patients following similar progressions in dosing of THC and CBD over time. χ2 tests were performed to identify which patient characteristics and qualifying medical conditions were associated with membership in each trajectory group. Six trajectory groups were identified that described different patterns in the THC and CBD doses that patients purchased over the whole time period. For THC, the majority of patients (62.6%) purchased a steady amount but at different levels: consistently low (4.1 mg) or moderate (7.4 mg). Three groups, representing 22.0% together, exhibited doses that either fluctuate or constantly increase over time (5-20 mg). A final group of patients (15.8%) exhibited constant decrease in dose from 11 to 5 mg. For CBD, the data show similar trajectories, but at the generally higher values (4-16 mg). Patients with chronic pain, neuropathy, and cancer were overrepresented in groups where higher doses of THC were purchased over time. Patients with epilepsy had a higher representation in groups with higher doses of CBD across time. Results suggest heterogeneous dosing patterns and trajectories in the use of medical cannabis by patients with different medical conditions.

Ganglion Cell Complex Thickness and Visual Function in Chronic Leber Hereditary Optic Neuropathy.

To evaluate the correlation between the macular ganglion cell complex (GCC) thickness measured with manually corrected segmentation and visual function in individuals with chronic Leber hereditary optic neuropathy (LHON). Twenty-six chronic LHON subjects (60% treated with idebenone or Q10) from the Swedish LHON registry were enrolled. Best-corrected visual acuity (BCVA), visual field tests, and optical coherence tomography (OCT) were performed. Visual field was evaluated with the Haag-Streit Octopus 900 with the Esterman test and a custom 30° test. Canon OCT-HS100 scans were exported to the Iowa Reference Algorithm. GCC thickness was obtained after the segmentation was corrected manually in nine macular sectors. The GCC thickness was overestimated by 16 to 30 µm in different macular sectors with the automated segmentation compared with the corrected (P < 0.001). GCC thickness in all sectors showed significant correlation with all functional parameters. The strongest correlation was seen for the external temporal sector (BCVA: r = 0.604, P < 0.001; mean defect: r = 0.457, P = 0.001; Esterman score: r = 0.421, P = 0.003). No differences were seen between treated and untreated subjects with regard to GCC and visual field scores (P > 0.05), but BCVA was better among treated subjects (P = 0.017). The corrected GCC thickness showed correlation with visual function in chronic LHON subjects. The frequently occurring segmentation errors in OCT measurements related to chronic LHON can potentially be misleading in monitoring of disease progression and in evaluating the treatment effects. Precise measurements of GCC could serve as a sensitive tool to monitor structural changes in LHON. We therefore emphasize the importance of careful evaluation of the accuracy of OCT segmentation.

Protective effects of Boswellia and Curcuma extract on oxaliplatin-induced neuropathy via modulation of NF-κB signaling

Oxaliplatin is a third-generation anticancer agent with better efficacy, lower toxicity, and a broad spectrum of antineoplastic activity. Its use is frequently associated with chronic oxaliplatin-induced neuropathy (OIN), a cumulative phenomenon manifesting as loss of sensation, paresthesia, dysesthesia, and irresolvable fluctuations in proprioception that greatly affect the patients’ quality of life. The inevitable nature and high incidence of OIN, along with the absence of efficacious preventive agents, necessitate the development of effective and reliable protective options for limiting OIN while maintaining anticancer activity. The pathogenesis of chronic OIN involves neuroinflammation and oxidative stress. This study aimed to explore the neuroprotective effects of Boswellia serrata and Curcuma longa via modulation of nuclear factor-kappa B (NF-κB) signaling. Behavioral tests were conducted to assess cold allodynia, heat hyperalgesia, mechanical allodynia, mechanical hyperalgesia, and slowed nerve conduction velocity associated with chronic oxaliplatin administration. The modulation of NF-κB signaling and the subsequent activation of cytokines were evaluated through quantitative analysis of inflammatory cytokines in sciatic nerve homogenates. Additional assessments included oxidative stress parameters, serum neuronal biomarkers, and examination of sciatic nerve cross-sections. The findings indicate improvements in behavioral and biochemical parameters, as well as nerve histology, with the combined extract of Boswellia serrata and Curcuma longa at doses of 50 mg/kg and 75 mg/kg. Thus, this study presents evidence for the protective potential of the combined extract of Boswellia serrata and Curcuma longa in OIN through modulation of NF-κB signaling.

The Therapeutic Potential of Transdermal Gabapentin in the Symptomatic Management of Chronic Neuropathy

Standard pharmacotherapeutic options in the management of neuropathic pain are often poorly tolerated due to various contraindications, drug interactions, and troublesome adverse events. The investigation and pharmaceutical development of localized anti-neuropathic options is increasing among researchers and manufacturers, but results have not yet determined the role in therapy of transdermal/locally acting analgesics, anti-neuropathics, and anti-inflammatories. Compounding Pharmacies and FDA 503b Outsourcing Facilities aid in this critical endeavor through endogenous compounding and manufacturing (respectively) of transdermal analgesic formulations. This review summarizes the currently available clinical data supporting the implementation of transdermal gabapentin preparations in the management of chronic neuropathic symptoms. Transdermally applied analgesic, anti-inflammatory, and anti-neuropathic preparations are crucial in the development of pain management modalities which reduce the risk of numerous well-known complications, including drug-drug interactions, conflicting patient comorbidities, and CNS depressant effects. The adjunctive treatment of neuropathy with a transdermal analgesic/antispasmodic preparation remains under-investigated, and the role of these preparations in the management of chronic neuropathic pain remains unclear.

The Delayed Turnover of Proteasome Processing of Myocilin upon Dexamethasone Stimulation Introduces the Profiling of Trabecular Meshwork Cells' Ubiquitylome.

Glaucoma is chronic optic neuropathy whose pathogenesis has been associated with the altered metabolism of Trabecular Meshwork Cells, which is a cell type involved in the synthesis and remodeling of the trabecular meshwork, the main drainage pathway of the aqueous humor. Starting from previous findings supporting altered ubiquitin signaling, in this study, we investigated the ubiquitin-mediated turnover of myocilin (MYOC/TIGR gene), which is a glycoprotein with a recognized role in glaucoma pathogenesis, in a human Trabecular Meshwork strain cultivated in vitro in the presence of dexamethasone. This is a validated experimental model of steroid-induced glaucoma, and myocilin upregulation by glucocorticoids is a phenotypic marker of Trabecular Meshwork strains. Western blotting and native-gel electrophoresis first uncovered that, in the presence of dexamethasone, myocilin turnover by proteasome particles was slower than in the absence of the drug. Thereafter, co-immunoprecipitation, RT-PCR and gene-silencing studies identified STUB1/CHIP as a candidate E3-ligase of myocilin. In this regard, dexamethasone treatment was found to downregulate STUB1/CHIP levels by likely promoting its proteasome-mediated turnover. Hence, to strengthen the working hypothesis about global alterations of ubiquitin-signaling, the first profiling of TMCs ubiquitylome, in the presence and absence of dexamethasone, was here undertaken by diGLY proteomics. Application of this workflow effectively highlighted a robust dysregulation of key pathways (e.g., phospholipid signaling, β-catenin, cell cycle regulation) in dexamethasone-treated Trabecular Meshwork Cells, providing an ubiquitin-centered perspective around the effect of glucocorticoids on metabolism and glaucoma pathogenesis.

The Effects of Diabetes on Gas Transfer Capacity, Lung Volumes, Muscle Strength, and Cardio-pulmonary Responses During Exercise.

Diabetes is a risk factor for the development of vascular disease, chronic kidney disease, retinopathy, and neuropathy. Diabetes is a co-morbid condition commonly present in patients with respiratory disorders but the extent to which it influences ventilatory capacity, gas exchange, and functional capacity is not well known. Research question Does the presence of diabetes contribute to impairment in spirometry, gas transfer, and exercise capacity? Retrospective analysis of all subjects who performed incremental cardio-pulmonary exercise testing (CPET) between 1988 and 2012 at McMaster University Medical Centre. The impact of diabetes on physiological outcomes and maximum power output (MPO) was assessed using stepwise multiple additive linear regression models including age, height, weight, sex, muscle strength, and previous myocardial infarct as co-variates, and was also stratified based on BMI categories. 40,776 subjects were included in the analysis; 1938 (5%, 66% male) had diabetes. Diabetics were older (59 vs. 53 years), heavier (88.3 vs.78.0 kg), and had a higher BMI (31 vs. 27kg/m2). The presence of diabetes was independently associated with a reduction in FEV1 (-130ml), FVC (-220ml), DLCO (-1.52ml/min/mmHg), and VA (-340ml) but not KCO. Patients with diabetes achieved a lower % predicted MPO[diabetic subjects 70% predicted (670 kpm/min ± 95% CI 284) vs. 80% in non-diabetics (786 kpm/min ± 342), p < 0.001]. With the exception of KCO, these differences persisted across BMI categories and after adjusting for MI. The presence of diabetes is independently associated with weaker muscles, lower ventilatory and gas transfer capacity and translates to a lower exercise capacity. These differences are independent of age, height, weight, sex, and previous MI.

Inflammatory Optic Neuropathy

Optic neuritis is the primary inflammation of the optic nerve. Chronic Recurrent Isolated Optic Neuropathy is an inflammatory optic neuropathy characterized by its recurrent and/or chronic nature, as well as corticosteroid sensitivity. Relapses that occur after the reduction or cessation of steroids and more severe visual loss compared to demyelinating optic neuritis are characteristic features. Although patients initially tend to respond well to steroids, cumulative damage can lead to poor visual outcomes and permanent loss of the retinal nerve fiber layer and ganglion cell layer. Diagnosing inflammatory optic neuropathies is crucial, as maintenance immunosuppressive therapy should be initiated in patients with relapses to protect against permanent vision loss in many types.

Fluorescein Angiography for Monitoring Neural Blood Flow in Chronic Nerve Compression Neuropathy: Experimental Animal Models and Preliminary Clinical Observations.

Pathologies associated with neural blood disturbance have been reported in patients with chronic nerve compression (CNC) neuropathy. Fluorescein angiography (FAG) and laser Doppler flowmetry (LDF) are effective for real-time peripheral nerve blood flow assessment. However, their reliability in severe neuropathy models in large animals or clinical conditions remains unclear. Initially, we aim to apply FAG to two different CNC animal models and evaluate their characteristics in comparison with those of LDF. In FAG, we quantified the peak luminance at the compression site following fluorescein injection. Then, we positioned the LDF probe at the center of the compression site and recorded the blood flow. Subsequently, we analyzed whether the FAG characteristics obtained in this animal experiment were consistent with those of clinical studies in patients with severe carpal tunnel syndrome (CTS). In the CNC rat model, FAG and LDF effectively monitored reduced neural blood flow over time. We observed significant blood flow reduction using both techniques in a newly developed severe CNC rabbit model. Notably, FAG correlated strongly with the compound muscle action potential (CMAP) amplitude in electrodiagnostic findings, unlike LDF. As a next step, we performed FAG after open carpal tunnel release in clinical cases of CTS. FAG correlated significantly with preoperative CMAP amplitude. This indicates FAG's importance for assessing nerve blood flow during surgery, potentially improving diagnostic accuracy and surgical outcomes.

Exploring Analgesic Use Patterns Among Cancer Survivors With Chronic Chemotherapy-Induced Peripheral Neuropathy.

To explore cancer survivors' historical and current use of analgesics for chronic chemotherapy-induced peripheral neuropathy (CIPN). 142 post-treatment cancer survivors who received neurotoxic chemotherapy and were experiencing moderate to severe CIPN. Participants completed the Treatment-Induced Neuropathy Assessment Scale at baseline and reported all analgesics used to manage CIPN. Frequency of historical or current prescription analgesic use for chronic CIPN was described and stratified by CIPN pain severity. At baseline, 31% of participants reported historical use of analgesics for CIPN and 46% of participants were currently using analgesics for CIPN. Gabapentin was the most frequently used analgesic, historically (20%) and currently (34%), and duloxetine was used less frequently (6% historical use, 10% current use). Many participants with severe pain (59%) reported using analgesics for CIPN. Duloxetine, the first-line treatment for chronic CIPN pain, was used less frequently than gabapentin, a common prescription analgesic for neuropathic pain. Further research is needed to determine strategies to promote the implementation of evidence-based CIPN treatments in clinical practice.

Antibodies in Autoimmune Neuropathies: What to Test, How to Test, Why to Test.

Autoimmune neuropathies are a heterogeneous group of immune-mediated disorders of the peripheral nerves. Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are the archetypal acute and chronic forms. Over the past few decades, pathogenic antibodies targeting antigens of the peripheral nervous system and driving peripheral nerve damage in selected patients have been described. Moreover, the detection of these antibodies has diagnostic and therapeutic implications that have prompted a modification of the GBS and CIDP diagnostic algorithms. GBS diagnosis is based in clinical criteria, and systematic testing of anti-ganglioside antibodies is not required. Nonetheless, a positive anti-ganglioside antibody test may support the clinical suspicion when diagnosis of GBS (GM1 IgG), Miller Fisher (GQ1b IgG), or acute sensory-ataxic (GD1b IgG) syndromes is uncertain. Anti-myelin-associated glycoprotein (MAG) IgM and anti-disialosyl IgM antibodies are key in the diagnosis of anti-MAG neuropathy and chronic ataxic neuropathy, ophthalmoplegia, M-protein, cold agglutinins, and disialosyl antibodies spectrum neuropathies, respectively, and help differentiating these conditions from CIDP. Recently, the field has been boosted by the discovery of pathogenic antibodies targeting proteins of the node of Ranvier contactin-1, contactin-associated protein 1, and nodal and paranodal isoforms of neurofascin (NF140, NF186, or NF155). These antibodies define subgroups of patients with specific clinical (most importantly poor or partial response to conventional therapies and excellent response to anti-CD20 therapy) and pathologic (node of Ranvier disruption in the absence of inflammation) features that led to the definition of the "autoimmune nodopathy" diagnostic category and to the incorporation of nodal/paranodal antibodies to clinical routine testing. The purpose of this review was to provide a practical vision for the general neurologist of the use of antibodies in the clinical assessment of autoimmune neuropathies.

Screening Strategies and Methodologies.

While glaucoma is a leading cause of irreversible vision loss, it presents technical challenges in the design and implementation of screening. New technologies such as PRS and AI offer potential improvements in our ability to identify people at high risk of sight loss from glaucoma and may improve the viability of screening for this important disease. To review the current evidence and concepts around screening for glaucoma. A group of glaucoma-focused clinician scientists drew on knowledge and experience around glaucoma, its etiology, and the options for screening. Glaucoma is a chronic progressive optic neuropathy affecting around 76 million individuals worldwide and is the leading cause of irreversible blindness globally. Early stages of the disease are asymptomatic meaning a substantial proportion of cases remain undiagnosed. Early detection and timely intervention reduce the risk of glaucoma-related visual morbidity. However, imperfect tests and a relatively low prevalence currently limit the viability of population-based screening approaches. The diagnostic yield of opportunistic screening strategies, relying on the identification of disease during unrelated health care encounters, such as cataract clinics and diabetic retinopathy screening programs, focusing on older people and/or those with a family history, are hindered by a large number of false-positive and false-negative results. Polygenic risk scores (PRS) offer personalized risk assessment for adult-onset glaucoma. In addition, artificial intelligence (AI) algorithms have shown impressive performance, comparable to expert humans, in discriminating between potentially glaucomatous and non-glaucomatous eyes. These emerging technologies may offer a meaningful improvement in diagnostic yield in glaucoma screening. While glaucoma is a leading cause of irreversible vision loss, it presents technical challenges in the design and implementation of screening. New technologies such as PRS and AI offer potential improvements in our ability to identify people at high risk of sight loss from glaucoma and may improve the viability of screening for this important disease.