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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 -
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 -
Journal of Diabetes Investigation Jun 2024To investigate risk factors for diabetic peripheral neuropathy (DPN) and to explore the connection between insulin-like growth factor-1 (IGF-1) and DPN in individuals...
AIMS/INTRODUCTION
To investigate risk factors for diabetic peripheral neuropathy (DPN) and to explore the connection between insulin-like growth factor-1 (IGF-1) and DPN in individuals with type 2 diabetes.
MATERIALS AND METHODS
A total of 790 patients with type 2 diabetes participated in a cross-sectional study, divided into two groups: those with DPN (DPN) and those without DPN (non-DPN). Blood samples were taken to measure IGF-1 levels and other biochemical markers. Participants underwent nerve conduction studies and quantitative sensory testing.
RESULTS
Patients with DPN exhibited significantly lower levels of IGF-1 compared with non-DPN patients (P < 0.001). IGF-1 was positively correlated with the average amplitude of both motor (P < 0.05) and sensory nerves (P < 0.05), but negatively correlated with the vibration perception threshold (P < 0.05). No significant difference was observed between IGF-1 and nerve conduction velocity (P > 0.05), or the temperature detection threshold (P > 0.05). Multivariate regression analysis identified diabetes duration, HbA, and the low levels of IGF-1 as independent risk factors (P < 0.001). Receiver operating characteristic analysis determined that at 8 years duration of diabetes, 8.5% (69.4 mmol/mol) HbA and 120 ng/mL IGF-1, the optimal cut-off points, indicated DPN (P < 0.001).
CONCLUSIONS
A reduction of IGF-1 in patients with DPN suggests a potential protective role against axon injury in large fiber nerves of type 2 diabetes patients.
PubMed: 38923403
DOI: 10.1111/jdi.14260 -
Current Oncology (Toronto, Ont.) Jun 2024Involvement of the recurrent laryngeal nerve (RLN) in papillary thyroid carcinoma (PTC) is an important prognostic factor and is associated with a higher risk of...
The Effect of Hemithyroidectomy in Papillary Thyroid Carcinoma with an Exclusive Involvement of the Recurrent Laryngeal Nerve: A Retrospective Study with a Propensity Score-Matched Analysis.
BACKGROUND
Involvement of the recurrent laryngeal nerve (RLN) in papillary thyroid carcinoma (PTC) is an important prognostic factor and is associated with a higher risk of recurrence. This study aimed to retrospectively analyze the outcomes of patients treated with hemithyroidectomy (HT) in PTC patients with an exclusive RLN invasion who could not tolerate staged surgery, did not wish to undergo another operation, or had other reasons.
METHODS
A retrospective review was conducted on 163 patients with PTC and exclusive RLN involvement at our institution between 2013 and 2019. Patients were divided into a total thyroidectomy (TT) group and HT group. The clinicopathologic factors and prognostic outcomes were compared between the two groups. A propensity score-matched analysis was carried out to reduce selection bias, with the following covariates: gender, age, tumor size, multifocality, central lymph node metastasis (CLNM), and RLN resection. The Kaplan-Meier method was used for a comparison of recurrence outcomes.
RESULTS
In the baseline data of the 163 PTC patients, tumor size ( < 0.001), multifocality ( = 0.011), CLNM ( < 0.001), and RLN resection ( < 0.008) in the TT and HT groups differed significantly, whereas age and gender did not differ between the two groups. The TT group reported significantly higher temporary and permanent hypoparathyroidism than the HT group ( < 0.001 and = 0.042, respectively). With 72-month median follow-up, 11 (6.7%) patients developed recurrence. After propensity score matching, 24 patients with HT and 43 patients with TT were included. Recurrence-free survival (RFS) in the matched samples showed no difference between the TT and HT groups ( = 0.092).
CONCLUSION
Our results indicate that HT may be a feasible treatment for PTC patients with exclusive RLN involvement in specific circumstances without significantly increasing the risk of recurrence. Performing a thorough preoperative examination is crucial to exclude multifocal tumors and lymph node metastasis before undergoing HT.
Topics: Humans; Male; Retrospective Studies; Female; Thyroid Cancer, Papillary; Propensity Score; Thyroidectomy; Middle Aged; Adult; Thyroid Neoplasms; Recurrent Laryngeal Nerve; Neoplasm Recurrence, Local; Aged
PubMed: 38920748
DOI: 10.3390/curroncol31060265 -
Cells Jun 2024Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with...
Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with tumor cells or other components of the tumor microenvironment (TME) remains elusive. We established an SC-related 43-gene set as a surrogate for peripheral nerves in the TME. Head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA) were classified into low, intermediate and high SC score groups based on the expression of this gene set. Perineural invasion (PNI) and TGF-β signaling were hallmarks of SC tumors, whereas SC tumors were enriched for HPV16-positive OPSCC and higher PI3K-MTOR activity. The latter activity was partially explained by a higher frequency of mutation and copy number gain. The inverse association between PI3K-MTOR activity and peripheral nerve abundance was context-dependent and influenced by the mutation status. An in silico drug screening approach highlighted the potential vulnerabilities of HNSCC with variable SC scores and predicted a higher sensitivity of SC tumors to DNA topoisomerase inhibitors. In conclusion, we have established a tool for assessing peripheral nerve abundance in the TME and provided new clinical and biological insights into their regulation. This knowledge may pave the way for new therapeutic strategies and impart proof of concept in appropriate preclinical models.
Topics: Humans; Tumor Microenvironment; Squamous Cell Carcinoma of Head and Neck; Phosphatidylinositol 3-Kinases; Signal Transduction; Peripheral Nerves; Head and Neck Neoplasms; Mutation; TOR Serine-Threonine Kinases; Class I Phosphatidylinositol 3-Kinases; Schwann Cells; PTEN Phosphohydrolase; Gene Expression Regulation, Neoplastic; Tumor Suppressor Protein p53
PubMed: 38920662
DOI: 10.3390/cells13121033 -
Cells Jun 2024Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While... (Review)
Review
Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While OPCs are highly proliferative during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions, including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated; they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar-a barrier mainly formed by reactive astrocytes, microglia and the deposition of inhibitory extracellular matrix components. If, on the one hand, a glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered the glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.
Topics: Humans; Remyelination; Animals; Oligodendrocyte Precursor Cells; Cicatrix; Neuroglia; Oligodendroglia; Myelin Sheath; Cell Differentiation
PubMed: 38920654
DOI: 10.3390/cells13121024 -
Drug Design, Development and Therapy 2024Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study Clinical Trial
Comparison of Ciprofol-Based and Propofol-Based Total Intravenous Anesthesia on Microvascular Decompression of Facial Nerve with Neurophysiological Monitoring: A Randomized Non-Inferiority Trial.
PURPOSE
Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM).
PATIENTS AND METHODS
This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes.
RESULTS
The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7±44.1 and 53.4±35.4, respectively. Furthermore, the 95% confidence interval of the difference was -25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P<0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P<0.05).
CONCLUSION
Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect.
Topics: Humans; Propofol; Male; Middle Aged; Female; Single-Blind Method; Microvascular Decompression Surgery; Intraoperative Neurophysiological Monitoring; Facial Nerve; Anesthesia, Intravenous; Anesthetics, Intravenous; Aged; Adult
PubMed: 38919963
DOI: 10.2147/DDDT.S459618 -
Neuropsychiatric Disease and Treatment 2024We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to...
PURPOSE
We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to dementia, and its underlying mechanisms of action.
PATIENTS AND METHODS
This was a prospective open-label observational pilot study at Daejeon Korean Medicine Hospital of Daejeon University in South Korea from March 2022 to March 2023. We included six Korean patients (50% male) aged ≥ 45 years and < 85 years with MCI, a clinical dementia rating score of 0.5, and a Montreal Cognitive Assessment-Korea (MoCA-K) score ≤ 22. The exclusion criterion was impaired cognitive function. Patients received combined therapy, including a herbal formula and EA, for 12-24 weeks. We prescribed the herbal formulas Gamiguibi-tang, Yukmijihwang-tang, and Banhasasim-tang to the patients for at least 70% of the treatment period, in combination with EA. Moreover, we investigated changes in cognitive and cognition-related symptoms and cytokine expression in the blood following combined traditional medicine therapy. At baseline and after 12 and 24 weeks, we administered the MoCA-K and cognitive-related questionnaires. We analyzed network pharmacology to reflect the herbal formula intervention mechanism comprehensively.
RESULTS
The median score [interquartile range] of MoCA-K at baseline was 19.5 [16.0, 22.0], which improved significantly (24.5 [24.0, 26.0], < 0.01) over 24 weeks following combined therapy. We obtained no significant conclusion regarding cytokine changes due to the small sample size. In network pharmacology, we analyzed the brain, head, heart, peripheral nerves, peripheral nervous system, and pancreas as the enriched organs from the common targets of the three herbal formulas.
CONCLUSION
Combined herbal medicine and EA improved cognitive function in patients with MCI. We assume the underlying mechanism of herbal formulas to be antioxidative and anti-inflammatory changes in cytokine expression. Combined traditional medicine has potential therapeutic application in preventing MCI progression to dementia.
PubMed: 38919562
DOI: 10.2147/NDT.S465650