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BMC Pediatrics Jun 2024Guillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral...
BACKGROUND
Guillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral nerves. Anti-sulfatide antibody-mediated complement is associated with acute sensorimotor peripheral neuropathy in GBS, which is characterized by pain and paresthesias.
CASE PRESENTATION
The child was a 7-year-old girl with headache and abdominal pain, followed by limb numbness and pain. Cranial imaging showed ventricular dilatation, peripheral nerve function conduction examination showed polyradiculopathy, and cerebrospinal fluid tests showed normal cell counts but elevated protein levels, all of which led to the diagnosis of GBS. After treatment with intravenous immunoglobulin (400 mg/kg × 5 days), the symptoms did not improve, and muscle strength progressively worsened, accompanied by paroxysmal complexion flushing, heart rate fluctuation, hyperhidrosis, and a progressive increase in cerebrospinal fluid protein (up to 3780.1 mg/L). On the basis of these findings combined with serum anti-sulfatide IgM positivity, anti-sulfatide antibody-related GBS was considered, and treatment with low-dose prednisolone (1 mg/kg/d) led to symptom improvement.
CONCLUSIONS
Anti-sulfatide antibody-associated GBS is associated with small fiber peripheral neuropathy. The main manifestations are pain, paresthesias and autonomic dysfunction. In addition to the dysfunction of spinal nerve root absorption caused by increased cerebrospinal fluid protein, autonomic dysfunction may be involved in pain. When the therapeutic effect of immunoglobulin is not satisfactory, a low dose and short course of corticosteroids can be considered, and the prognosis is good.
Topics: Humans; Female; Child; Guillain-Barre Syndrome; Abdominal Pain; Headache; Sulfoglycosphingolipids; Autoantibodies; Prednisolone
PubMed: 38926645
DOI: 10.1186/s12887-023-04287-5 -
Nature Communications Jun 2024B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein...
B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein (MOG). Here, we show that upon immunization with the T cell-obligate autoantigen, MOG, IgH mice develop rapid and exacerbated experimental autoimmune encephalomyelitis (EAE) relative to wildtype (WT) counterparts, characterized by aggregation of T and B cells in the IgH meninges and by CD4 T helper 17 (Th17) cells in the CNS. Production of the Th17 maintenance factor IL-23 is observed from IgH CNS-infiltrating and meningeal B cells, and in vivo blockade of IL-23p19 attenuates disease severity in IgH mice. In the CNS parenchyma and dura mater of IgH mice, we observe an increased frequency of CD4PD-1CXCR5 T cells that share numerous characteristics with the recently described T peripheral helper (Tph) cell subset. Further, CNS-infiltrating B and Tph cells from IgH mice show increased reactive oxygen species (ROS) production. Meningeal inflammation, Tph-like cell accumulation in the CNS and B/Tph cell production of ROS were all reduced upon p19 blockade. Altogether, MOG-specific B cells promote autoimmune inflammation of the CNS parenchyma and meninges in an IL-23-dependent manner.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; B-Lymphocytes; Myelin-Oligodendrocyte Glycoprotein; Mice; Autoimmunity; Interleukin-23; CD4-Positive T-Lymphocytes; Th17 Cells; Central Nervous System; Mice, Inbred C57BL; Female; Myelin Sheath; Meninges; Multiple Sclerosis
PubMed: 38926356
DOI: 10.1038/s41467-024-49259-0 -
International Ophthalmology Jun 2024The aim of this study was to evaluate the lamina cribrosa curvature index in different types of glaucoma in comparison with clinical findings and conventional...
OBJECTIVE
The aim of this study was to evaluate the lamina cribrosa curvature index in different types of glaucoma in comparison with clinical findings and conventional measurement methods.
MATERIAL AND METHOD
Patients older than 18 years who were followed up in Glaucoma Unit of Department of Ophthalmology at Fırat University Faculty of Medicine, whose disease had been under control at least for 1 year, who had at least three reliable visual fields, whose refractive error was between - 6 and + 5 diopter and who did not have any disease other than glaucoma that would affect the visual field, were included in the study. Clinical and demographic characteristics, visual field, optical coherence tomography and lamina cribrosa curvature index (LCCI) results were evaluated. The study patients were divided into six groups: early-stage primary open-angle glaucoma (POAG) as group 1 and intermediate-advanced stage POAG as group 2, pseudo-exfoliation glaucoma (PEXG) as group 3, normal tension glaucoma (NTG) as group 4, ocular hypertension patients whom subsequently developed POAG as group 5 and healthy control as group 6.
RESULTS
A total of 189 eyes of 101 patients were included in our study. Forty-seven patients were male (46.5%) and 54 were female (53.5%). The mean age was 62.43 ± 1.49 years. LCCI, mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD) and retinal nerve fiber layer thickness (RNFL) values were analyzed in all groups and Pearson correlation analysis showed statistically significant correlation between PSD and RNFL measurements with LCCI values in all groups. MD value was correlated with LCCI in groups 2, 3 and 4, while VFI value was correlated with LCCI in all groups except group 5. When the groups were compared with each other according to the Post-Hoc Tamhane test, LCCI measurement showed statistically significant results in accordance with MD, VFI, PSD and RNFL values.
CONCLUSION
The LCCI assessment is mostly consistent with conventional tests. In this study, in which different types of glaucoma and healthy subjects were examined simultaneously, LCCI shows promise as a detailed and reliable assessment method.
Topics: Humans; Male; Female; Tomography, Optical Coherence; Middle Aged; Visual Fields; Optic Disk; Intraocular Pressure; Aged; Glaucoma, Open-Angle; Retinal Ganglion Cells; Nerve Fibers; Adult; Follow-Up Studies; Glaucoma
PubMed: 38926206
DOI: 10.1007/s10792-024-03190-x -
Canadian Journal of Surgery. Journal... 2024Understanding patterns of peripheral nerve injuries (PNIs) and brachial plexus injuries (BPIs) is essential to preventing and appropriately managing nerve injuries. We...
BACKGROUND
Understanding patterns of peripheral nerve injuries (PNIs) and brachial plexus injuries (BPIs) is essential to preventing and appropriately managing nerve injuries. We sought to assess the incidence, cause, and severity of PNIs and BPIs sustained by patients with trauma.
METHODS
We conducted a retrospective review of the Trauma Registry Database (January 2002 to December 2020) to identify patients with PNIs or BPIs.
RESULTS
We evaluated data from 24 905 patients with trauma; 335 (1.3%) sustained PNIs (81% male; mean age 36 yr, standard deviation [SD] 16 yr) and 64 (0.3%) sustained BPIs (84% male; mean age 35, SD 15 yr). Nerves in the upper extremities were more commonly affected than those in the lower extremities. Sharp injuries (39.4%) and motorcycle accidents (32.8%) were the most frequent causes of PNIs and BPIs, respectively. Other common causes of PNI were motor vehicle collisions (16.7%) and gunshot wounds (12.8%). Many patients with PNIs (69.0%) and BPIs (53%) underwent operative management. The most frequent reconstruction for PNI was primary nerve repair (66%), while nerve transfers (48%) were more frequently used for BPI.
CONCLUSION
Nerve injuries in the trauma population have decreased over the last 3 decades with shifts in mechanisms of injury and use of imaging, electrodiagnostic tests, and surgery. Nerve injuries are often complex and time-sensitive to treat; understanding changes in trends is important to ensure optimal patient management.
Topics: Humans; Male; Adult; Peripheral Nerve Injuries; Female; Retrospective Studies; Brachial Plexus; Middle Aged; Incidence; Young Adult; Registries; Accidents, Traffic; Adolescent
PubMed: 38925857
DOI: 10.1503/cjs.002424 -
Anticancer Research Jul 2024Chemotherapy-induced peripheral neuropathy (CIPN) continues to be a major source of chronic morbidity in patients with cancer. Current treatment options and efficacy are... (Review)
Review
BACKGROUND/AIM
Chemotherapy-induced peripheral neuropathy (CIPN) continues to be a major source of chronic morbidity in patients with cancer. Current treatment options and efficacy are limited; thus, there is a need to investigate more effective therapeutic options. Spinal neuromodulation including dorsal column spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRG-S) are being explored for these patients. The purpose of this narrative review was to critically summarize and evaluate the advancements that have been made in utilizing SCS and DRG-S for CIPN.
MATERIALS AND METHODS
A thorough literature search was conducted using PubMed for any research on patients with CIPN who underwent DRG-S or SCS. Studies involving patients with general cancer-related pain were not included. Only articles that were published in English, had original, extractable data, and were available on or before August 1, 2023, were included.
RESULTS
This study evaluated twelve studies with a total of 13 patients that reported using SCS for CIPN and four studies with a total of 12 patients that reported using DRG-S for CIPN. Many of the studies demonstrated that DRG-S or SCS can assist in reducing opioid consumption, lowering pain scores, and improving sensory deficits.
CONCLUSION
DRG-S and SCS have the potential to improve symptoms and lower medication usage in patients suffering from CIPN. Spinal neuromodulation could be considered as an alternative therapy for patients with persistent symptoms.
Topics: Humans; Peripheral Nervous System Diseases; Spinal Cord Stimulation; Antineoplastic Agents; Ganglia, Spinal; Neoplasms; Pain Management
PubMed: 38925845
DOI: 10.21873/anticanres.17088 -
Pharmacological Research Jun 2024Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors...
Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines and nerve injury. Both male and female mice developed dose-dependent mechanical hypersensitivity in response to ephrin-B2, and both sexes showed hyperalgesic priming when challenged with PGE injection either to the paw or the cranial dura. Acute nociceptive behaviors and hyperalgesic priming were blocked in mice lacking MNK1 (Mknk1 knockout mice) and by eFT508, a specific MNK inhibitor. Sensory neuron-specific knockout of EphB2 using Pirt-Cre demonstrated that ephrin-B2 actions require this receptor. In Ca-imaging experiments on cultured DRG neurons, ephrin-B2 treatment enhanced Ca transients in response to PGE and these effects were absent in DRG neurons from MNK1 and EphB2-Pirt mice. In experiments on human DRG neurons, ephrin-B2 increased eIF4E phosphorylation and enhanced Ca responses to PGE treatment, both blocked by eFT508. We conclude that ephrin-B2 acts directly on mouse and human sensory neurons to induce nociceptor plasticity via MNK-eIF4E signaling, offering new insight into how ephrin-B signaling promotes pain.
PubMed: 38925462
DOI: 10.1016/j.phrs.2024.107284 -
Neurology(R) Neuroimmunology &... Sep 2024Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct CNS demyelinating disease. The rate of asymptomatic optic nerve enhancement on MRI...
BACKGROUND AND OBJECTIVES
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct CNS demyelinating disease. The rate of asymptomatic optic nerve enhancement on MRI has not been explored in patients with MOGAD. An improved understanding of this would guide clinical practice and assessment of treatment efficacy. We aimed to determine the frequency of asymptomatic optic nerve enhancement in MOGAD.
METHODS
This was a retrospective review of patients evaluated at Mayo Clinic with MOGAD between January 1, 2000, and August 1, 2021 (median follow-up 1.6 [range 1-19] years). MRI studies were reviewed by masked neuroradiologists. Scans performed within 30 days of ON attack were classified as attack scans. Images obtained for routine surveillance, before ON attack, or at the time of non-ON attack were classified as interattack scans.
RESULTS
Five hundred sixty-six MRIs (203 unique patients, 53% female) were included. Interattack MRIs represented 341 (60%) of the scans (median 36 days post-ON [range -1,032 to 6,001]). Of the interattack scans, 43 of 341 (13%), 30 unique patients, showed optic nerve enhancement. The enhancement was located at prior sites of ON in 35 of 43 (81%). Among the 8 patients with enhancement in new optic nerve areas, 6 had acute disseminated encephalomyelitis without an eye examination at the time of the MRI and 2 had preceding ON without imaging. Long-term visual outcomes showed no significant difference between those with and without asymptomatic enhancement, with improved visual acuity in most patients.
DISCUSSION
Asymptomatic optic nerve enhancement occurred in 13% of interattack MRIs, the majority in patients with prior ON and occurring at prior sites of optic nerve enhancement. New asymptomatic optic nerve enhancement in areas without prior ON was rare. These findings are important for understanding the natural history of MOGAD, the interpretation of symptoms or response to treatment, and the adjudication of attacks in clinical trials.
Topics: Humans; Female; Male; Adult; Myelin-Oligodendrocyte Glycoprotein; Retrospective Studies; Magnetic Resonance Imaging; Middle Aged; Young Adult; Optic Nerve; Adolescent; Aged; Child; Autoantibodies; Demyelinating Autoimmune Diseases, CNS; Child, Preschool; Asymptomatic Diseases; Aged, 80 and over
PubMed: 38924706
DOI: 10.1212/NXI.0000000000200277 -
Science Translational Medicine Jun 2024Congenital pseudarthrosis of the tibia (CPT) is a severe pathology marked by spontaneous bone fractures that fail to heal, leading to fibrous nonunion. Half of patients...
Congenital pseudarthrosis of the tibia (CPT) is a severe pathology marked by spontaneous bone fractures that fail to heal, leading to fibrous nonunion. Half of patients with CPT are affected by the multisystemic genetic disorder neurofibromatosis type 1 (NF1) caused by mutations in the tumor suppressor gene, a negative regulator of RAS-mitogen-activated protein kinase (MAPK) signaling pathway. Here, we analyzed patients with CPT and knockout mice to elucidate the pathogenic mechanisms of CPT-related fibrous nonunion and explored a pharmacological approach to treat CPT. We identified -deficient Schwann cells and skeletal stem/progenitor cells (SSPCs) in pathological periosteum as affected cell types driving fibrosis. Whereas -deficient SSPCs adopted a fibrotic fate, -deficient Schwann cells produced critical paracrine factors including transforming growth factor-β and induced fibrotic differentiation of wild-type SSPCs. To counteract the elevated RAS-MAPK signaling in both -deficient Schwann cells and SSPCs, we used MAPK kinase (MEK) and Src homology 2 containing protein tyrosine phosphatase 2 (SHP2) inhibitors. Combined MEK-SHP2 inhibition in vivo prevented fibrous nonunion in the knockout mouse model, providing a promising therapeutic strategy for the treatment of fibrous nonunion in CPT.
Topics: Animals; Schwann Cells; Pseudarthrosis; Neurofibromin 1; Humans; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Mice, Knockout; Stem Cells; Tibia; Mice; Cell Differentiation; Male; Neurofibromatosis 1; Fibrosis; Female; Mitogen-Activated Protein Kinase Kinases
PubMed: 38924432
DOI: 10.1126/scitranslmed.adj1597 -
Journal of Biomedical Materials... Jul 2024Sensorineural hearing loss (SNHL) is mainly caused by injury or loss of hair cells (HCs) and associated spiral ganglion neurons (SGNs) in the inner ear. At present,...
Sensorineural hearing loss (SNHL) is mainly caused by injury or loss of hair cells (HCs) and associated spiral ganglion neurons (SGNs) in the inner ear. At present, there is still no effective treatment for SNHL in clinic. Recently, advances in organoid bring a promising prospect for research and treatment of SNHL. Meanwhile, three-dimensional (3D) printing provides a tremendous opportunity to construct versatile organoids for tissue engineering and regenerative medicine. In this study, gelatin (Gel), sodium alginate (SA), and polyvinyl alcohol (PVA) were used to fabricate biomimetic scaffold through 3D printing. The organ of Corti derived from neonatal mice inner ear was seeded on the PVA/Gel/SA scaffold to construct organ of Corti organoid. Then, the organ of Corti organoid was used to study the potential protective effects of berberine sulfate on neomycin-juried auditory HCs and SGNs. The results showed that the PVA/Gel/SA biomimetic 3D scaffolds had good cytocompatibilities and mechanical properties. The constructed organoid could maintain organ of Corti activity well in vitro. In addition, the injury intervention results showed that berberine sulfate could significantly inhibit neomycin-induced HC and SGN damage. This study suggests that the fabricated organoid is highly biomimetic to the organ of Corti, which may provide an effective model for drug development, cell and gene therapy for SNHL.
Topics: Animals; Organ of Corti; Mice; Berberine; Tissue Scaffolds; Organoids; Printing, Three-Dimensional; Alginates; Gelatin; Hair Cells, Auditory; Tissue Engineering; Polyvinyl Alcohol; Hearing Loss, Sensorineural; Spiral Ganglion
PubMed: 38923766
DOI: 10.1002/jbm.b.35439 -
Annals of Neurology Jun 2024Amyloid neuropathy is caused by deposition of insoluble β-pleated amyloid sheets in the peripheral nervous system. It is most common in: (1) light-chain amyloidosis, a... (Review)
Review
Amyloid neuropathy is caused by deposition of insoluble β-pleated amyloid sheets in the peripheral nervous system. It is most common in: (1) light-chain amyloidosis, a clonal non-proliferative plasma cell disorder in which fragments of immunoglobulin, light or heavy chain, deposit in tissues, and (2) hereditary transthyretin (ATTRv) amyloidosis, a disorder caused by autosomal dominant mutations in the TTR gene resulting in mutated protein that has a higher tendency to misfold. Amyloid fibrils deposit in the endoneurium of peripheral nerves, often extensive in the dorsal root ganglia and sympathetic ganglia, leading to atrophy of Schwann cells in proximity to amyloid fibrils and blood-nerve barrier disruption. Clinically, amyloid neuropathy is manifested as a length-dependent sensory predominant neuropathy associated with generalized autonomic failure. Small unmyelinated nerves are involved early and prominently in early-onset Val30Met ATTRv, whereas other ATTRv and light-chain amyloidosis often present with large- and small-fiber involvement. Nerve conduction studies, quantitative sudomotor axon testing, and intraepidermal nerve fiber density are useful tools to evaluate denervation. Amyloid deposition can be demonstrated by tissue biopsy of the affected organ or surrogate site, as well as bone-avid radiotracer cardiac imaging. Treatment of light-chain amyloidosis has been revolutionized by monoclonal antibodies and stem cell transplantation with improved 5-year survival up to 77%. Novel gene therapy and transthyretin stabilizers have revolutionized treatment of ATTRv, improving the course of neuropathy (less change in the modified Neuropathy Impairment Score + 7 from baseline) and quality of life. With great progress in amyloidosis therapies, early diagnosis and presymptomatic testing for ATTRv family members has become paramount. ANN NEUROL 2024.
PubMed: 38923548
DOI: 10.1002/ana.26965