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Voltage-gated sodium channels initiate action potentials in nerve, skeletal muscle, and other electrically excitable cells. Mutations in them cause a wide range of diseases. These channelopathy mutations affect every aspect of sodium channel function, including voltage sensing, voltage-dependent activation, ion conductance, fast and slow inactivation, and both biosynthesis and assembly. Mutations that cause different forms of periodic paralysis in skeletal muscle were discovered first and have provided a template for understanding structure, function, and pathophysiology at the molecular level. More recent work has revealed multiple sodium channelopathies in the brain. Here we review the well-characterized genetics and pathophysiology of the periodic paralyses of skeletal muscle and then use this information as a foundation for advancing our understanding of mutations in the structurally homologous α-subunits of brain sodium channels that cause epilepsy, migraine, autism, and related comorbidities. We include studies based on molecular and structural biology, cell biology and physiology, pharmacology, and mouse genetics. Our review reveals unexpected connections among these different types of sodium channelopathies.
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Encéfalo/fisiopatologia , Canalopatias/fisiopatologia , Músculo Esquelético/fisiopatologia , Canais de Sódio , Animais , Canalopatias/genética , Humanos , Camundongos , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/fisiopatologia , Canais de Sódio/genéticaRESUMO
Facial nerve regeneration still lacks a well-defined and practical clinical intervention. The survival of central facial motoneuron is a critical component in the successful peripheral facial nerve regeneration. Endogenous GDNF is vital for facial nerve regeneration according to earlier investigations. Nevertheless, the low endogenous GDNF level makes it challenging to achieve therapeutic benefits. Thus, we crushed the main trunk of facial nerve in SD rats to provide a model of peripheral facial paralysis, and we administered exogenous GDNF and Rapa treatments. We observed changes in the animal behavior scores, the morphology of facial nerve and buccinator muscle, the electrophysiological of facial nerve, and the expression of GDNF, GAP-43, and PI3K/AKT/mTOR signaling pathway-related molecules in the facial motoneurons. We discovered that GDNF could boost axon regeneration, hasten the recovery of facial paralysis symptoms and nerve conduction function, and increase the expression of GDNF, GAP-43, and PI3K/AKT/mTOR signaling pathway-related molecules in the central facial motoneurons. Therefore, exogenous GDNF injection into the buccinator muscle can enhance facial nerve regeneration following crushing injury and protect facial neurons via the PI3K/AKT/mTOR signaling pathway. This will offer a fresh perspective and theoretical foundation for the management of clinical facial nerve regeneration.
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Axônios , Nervo Facial , Ratos , Animais , Ratos Sprague-Dawley , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Proteína GAP-43 , Regeneração Nervosa/fisiologia , Neurônios Motores/fisiologia , Serina-Treonina Quinases TOR , Transdução de SinaisRESUMO
BACKGROUND: SARS-CoV-2 infections cause COVID-19 and are associated with inflammation, coagulopathy, and high incidence of thrombosis. Myeloid cells help coordinate the initial immune response in COVID-19. Although we appreciate that myeloid cells lie at the nexus of inflammation and thrombosis, the mechanisms that unite the two in COVID-19 remain largely unknown. METHODS: In this study, we used systems biology approaches including proteomics, transcriptomics, and mass cytometry to define the circulating proteome and circulating immune cell phenotypes in subjects with COVID-19. RESULTS: In a cohort of subjects with COVID-19 (n=35), circulating markers of inflammation (CCL23 [C-C motif chemokine ligand 23] and IL [interleukin]-6) and vascular dysfunction (ACE2 [angiotensin-converting enzyme 2] and TF [tissue factor]) were elevated in subjects with severe compared with mild COVID-19. Additionally, although the total white blood cell counts were similar between COVID-19 groups, CD14+ (cluster of differentiation) monocytes from subjects with severe COVID-19 expressed more TF. At baseline, transcriptomics demonstrated increased IL-6, CCL3, ACOD1 (aconitate decarboxylase 1), C5AR1 (complement component 5a receptor), C5AR2, and TF in subjects with severe COVID-19 compared with controls. Using stress transcriptomics, we found that circulating immune cells from subjects with severe COVID-19 had evidence of profound immune paralysis with greatly reduced transcriptional activation and release of inflammatory markers in response to TLR (Toll-like receptor) activation. Finally, sera from subjects with severe (but not mild) COVID-19 activated human monocytes and induced TF expression. CONCLUSIONS: Taken together, these observations further elucidate the pathological mechanisms that underlie immune dysfunction and coagulation abnormalities in COVID-19, contributing to our growing understanding of SARS-CoV-2 infections that could also be leveraged to develop novel diagnostic and therapeutic strategies.
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COVID-19 , Monócitos , Tromboplastina , Trombose , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , COVID-19/imunologia , COVID-19/sangue , COVID-19/complicações , Monócitos/imunologia , Monócitos/metabolismo , Proteômica/métodos , SARS-CoV-2/fisiologia , Tromboplastina/metabolismo , Tromboplastina/genética , Trombose/imunologia , Trombose/sangue , Trombose/etiologiaRESUMO
BACKGROUND: Sepsis is a life-threatening syndrome with complex pathophysiology and great clinical heterogeneity which complicates the delivery of personalized therapies. Our goals were to demonstrate that some biomarkers identified as regulatory immune checkpoints in preclinical studies could 1)improve sepsis prognostication based on clinical variables and 2)guide the stratification of septic patients in subgroups with shared characteristics of immune response or survival outcomes. METHODS: We assayed the soluble counterparts of 12 biomarkers of immune response in 113 internal medicine patients with bacterial sepsis. RESULTS: IL-1 receptor-associated kinase M (IRAK-M) exhibited the highest hazard ratios (HRs) for increased 7-day (1.94 [1.17-3.20]) and 30-day mortality (1.61 [1.14-2.28]). HRs of IRAK-M and Galectin-1 for predicting 1-year mortality were 1.52 (1.20-1.92) and 1.64 (1.13-2.36), respectively. A prognostic model including IRAK-M, Galectin-1, and clinical variables (Charlson Comorbidty Index, multiple source of sepsis, and SOFA score) had high discrimination for death at 7 days and 30 days (area under the curve 0.90 [0.82-0.99]) and 0.86 [0.79-0.94], respectively). Patients with elevated serum levels of IRAK-M and Galectin-1 had clinical traits of immune suppression and low survival rates. None of the 12 biomarkers were independent predictors of 2-year mortality. CONCLUSIONS: Two inhibitory immune checkpoint biomarkers (IRAK-M and Galectin-1) helped identify 3 distinct sepsis phenotypes with distinct prognoses. These biomarkers shed light on the interplay between immune dysfunction and prognosis in patients with bacterial sepsis and may prove to be useful prognostic markers, therapeutic targets, and biochemical markers for targeted enrollment in targeted therapeutic trials.
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Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 and its clinical impact during the fall-winter season of 2021/22. From 19 European countries, 58 institutes reported 10,481 (6.8%) EV-positive samples of which 1,004 (9.6%) were identified as EV-D68 (852 respiratory samples). Clinical data was reported for 969 cases. 78.9% of infections were reported in children (0-5 years); 37.9% of cases were hospitalised. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases with six reported with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of two novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale EV-D68 European upsurge with severe clinical impact and the emergence of B3-derived lineages.
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Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self-reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl-Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB-AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by .40 and 3.70 points from baseline to 1-week and 6-month post-surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1-week post-surgery, although partially recurred at 6-month follow-up. The average scores of WAB-AQ were increased by 9.14 and 10.69 points at 1-week and 6-month post-surgery (P < .001 for both), respectively. Post-surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries.
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Afasia , Transferência de Nervo , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Afasia/etiologia , Afasia/fisiopatologia , Adulto , Transferência de Nervo/métodos , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Idoso , Braço/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Espasticidade Muscular/cirurgia , Espasticidade Muscular/fisiopatologia , Espasticidade Muscular/etiologiaRESUMO
BACKGROUND & AIMS: Although transient bacteremia is common during dental and endoscopic procedures, infections developing during sterile diseases like acute pancreatitis (AP) can have grave consequences. We examined how impaired bacterial clearance may cause this transition. METHODS: Blood samples from patients with AP, normal controls, and rodents with pancreatitis or those administered different nonesterified fatty acids (NEFAs) were analyzed for albumin-unbound NEFAs, microbiome, and inflammatory cell injury. Macrophage uptake of unbound NEFAs using a novel coumarin tracer were done and the downstream effects-NEFA-membrane phospholipid (phosphatidylcholine) interactions-were studied on isothermal titration calorimetry. RESULTS: Patients with infected AP had higher circulating unsaturated NEFAs; unbound NEFAs, including linoleic acid (LA) and oleic acid (OA); higher bacterial 16S DNA; mitochondrial DNA; altered ß-diversity; enrichment in Pseudomonadales; and increased annexin V-positive myeloid (CD14) and CD3-positive T cells on admission. These, and increased circulating dead inflammatory cells, were also noted in rodents with unbound, unsaturated NEFAs. Isothermal titration calorimetry showed progressively stronger unbound LA interactions with aqueous media, phosphatidylcholine, cardiolipin, and albumin. Unbound NEFAs were taken into protein-free membranes, cells, and mitochondria, inducing voltage-dependent anion channel oligomerization, reducing ATP, and impairing phagocytosis. These were reversed by albumin. In vivo, unbound LA and OA increased bacterial loads and impaired phagocytosis, causing infection. LA and OA were more potent for these amphipathic interactions than the hydrophobic palmitic acid. CONCLUSIONS: Release of stored LA and OA can increase their circulating unbound levels and cause amphipathic liponecrosis of immune cells via uptake by membrane phospholipids. This impairs bacterial clearance and causes infection during sterile inflammation.
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Pancreatite , Humanos , Doença Aguda , Ácidos Graxos não Esterificados , Ácido Oleico , Inflamação , Albuminas , FosfatidilcolinasRESUMO
In 2014, 2016, and 2018, the United States experienced unprecedented spikes in pediatric cases of acute flaccid myelitis (AFM), which is a poliomyelitis-like paralytic illness. Accumulating clinical, immunological, and epidemiological evidence has identified enterovirus D68 (EV-D68) as a major causative agent of these biennial AFM outbreaks. There are currently no available FDA-approved antivirals that are effective against EV-D68, and the treatment for EV-D68-associated AFM is primarily supportive. Telaprevir is an food and drug administration (FDA)-approved protease inhibitor that irreversibly binds the EV-D68 2A protease and inhibits EV-D68 replication in vitro. Here, we utilize a murine model of EV-D68 associated AFM to show that early telaprevir treatment improves paralysis outcomes in Swiss Webster (SW) mice. Telaprevir reduces both viral titer and apoptotic activity in both muscles and spinal cords at early disease time points, which results in improved AFM outcomes in infected mice. Following intramuscular inoculation in mice, EV-D68 infection results in a stereotypic pattern of weakness that is reflected by the loss of the innervating motor neuron population, in sequential order, of the ipsilateral (injected) hindlimb, the contralateral hindlimb, and then the forelimbs. Telaprevir treatment preserved motor neuron populations and reduced weakness in limbs beyond the injected hindlimb. The effects of telaprevir were not seen when the treatment was delayed, and toxicity limited doses beyond 35 mg/kg. These studies are a proof of principle, provide the first evidence of benefit of an FDA-approved antiviral drug with which to treat AFM, and emphasize both the need to develop better tolerated therapies that remain efficacious when administered after viral infections and the development of clinical symptoms. IMPORTANCE Recent outbreaks of EV-D68 in 2014, 2016, and 2018 have resulted in over 600 cases of a paralytic illness that is known as AFM. AFM is a predominantly pediatric disease with no FDA-approved treatment, and many patients show minimal recovery from limb weakness. Telaprevir is an FDA-approved antiviral that has been shown to inhibit EV-D68 in vitro. Here, we demonstrate that a telaprevir treatment that is given concurrently with an EV-D68 infection improves AFM outcomes in mice by reducing apoptosis and viral titers at early time points. Telaprevir also protected motor neurons and improved paralysis outcomes in limbs beyond the site of viral inoculation. This study improves understanding of EV-D68 pathogenesis in the mouse model of AFM. This study serves as a proof of principle for the first FDA-approved drug that has been shown to improve AFM outcomes and have in vivo efficacy against EV-D68 as well as underlines the importance of the continued development of EV-D68 antivirals.
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Viroses do Sistema Nervoso Central , Enterovirus Humano D , Infecções por Enterovirus , Animais , Estados Unidos , Camundongos , Enterovirus Humano D/fisiologia , Modelos Animais de Doenças , Paralisia/tratamento farmacológico , Paralisia/etiologia , Infecções por Enterovirus/patologia , Antivirais/farmacologia , Antivirais/uso terapêuticoRESUMO
The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of vaccine-associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine-associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine-associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 [40.11%]) of vaccine-associated facial paralysis from 49 537 reports of all-cause facial paralysis. Vaccine-associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID-19) pandemic, which is attributable to the COVID-19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID-19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 [95% confidence interval, 27.60-29.03]; IC, 3.37 [IC0.25, 3.35]), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella-zoster, meningococcal, Ad-5 vectored COVID-19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole-virus COVID-19 vaccines. Concerning age- and sex-specific risks, vaccine-associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine-associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine-induced facial paralysis, primarily owing to COVID-19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine-associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.
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Bases de Dados Factuais , Paralisia Facial , Farmacovigilância , Organização Mundial da Saúde , Humanos , Paralisia Facial/epidemiologia , Paralisia Facial/etiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Criança , Pré-Escolar , Idoso , Incidência , Vacinas/efeitos adversos , Saúde Global , COVID-19/prevenção & controle , COVID-19/epidemiologia , Lactente , Vacinação/efeitos adversos , Vacinação/estatística & dados numéricos , SARS-CoV-2/imunologiaRESUMO
OBJECTIVES: It is well-known that long-term osteoarthritis prognosis is not improved by corticosteroid treatments. Here we investigate what could underlie this phenomenon by measuring the short term corticosteroid response of OA-Mf. METHODS: We determined the genome-wide transcriptomic response to corticosteroids of end-stage osteoarthritic joint synovial macrophages (OA-Mf). This was compared with LPS-tolerized and ß-glucan-trained circulating blood monocyte-derived macrophage models. RESULTS: Upon corticosteroid stimulation, the trained and tolerized macrophages significantly alter the abundance of 201 and 257 RNA transcripts, respectively. By contrast, by the same criteria, OA-Mf have a very restricted corticosteroid response of only 12 RNA transcripts. Furthermore, while metalloproteinases 1, -2, -3 and -10 expression clearly distinguish OA-Mf from both the tolerized and trained macrophage models, OA-Mf Interleukin 1 (IL1), chemokine (CXCL) and cytokine (CCL) family member profiles resemble the tolerized macrophage model, with the exception that OA-Mf show high levels of CCL20. CONCLUSION: Terminal osteoarthritis joints therefore harbor macrophages with an inflammatory state that closely resembles the tolerized macrophage state and this is compounded by a weak corticosteroid response capacity that may explain the lack of positive long-term effects of corticosteroid treatment for osteoarthritis patients.
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BACKGROUND: Facial paralysis due to parotid sialolithiasis-induced parotitis is a unusual clinical phenomenon that has not been reported in prior literature. This scenario can present a diagnostic challenge due to its rarity and complex symptomatology, particularly if a patient has other potential contributing factors such as facial trauma or bilateral forehead botox injections as in this patient. This case report elucidates such a complex presentation, aiming to increase awareness and promote timely recognition among clinicians. CASE PRESENTATION: A 56-year-old male, with a medical history significant for hyperlipidemia, recurrent parotitis secondary to parotid sialolithiasis, and recent bilateral forehead cosmetic Botox injections presented to the emergency department with right lower facial drooping. This onset was about an hour after waking up and was of 4 h duration. The patient also had a history of a recent ground level fall four days prior that resulted in facial trauma to his right eyebrow without any evident neurological deficits in the region of the injury. A thorough neurological exam revealed sensory and motor deficits across the entirety of the right face, indicating a potential lesion affecting the buccal and marginal mandibular branches of the facial nerve (CN VII). Several differential diagnoses were considered for the lower motor neuron lesion, including soft tissue trauma or swelling from the recent fall, compression due to the known parotid stone, stroke, and complex migraines. An MRI of the brain was conducted to rule out a stroke, with no significant findings. A subsequent CT scan of the neck revealed an obstructed and dilated right Stensen's duct with a noticeably larger and anteriorly displaced sialolith and evidence of parotid gland inflammation. A final diagnosis of facial palsy due to parotitis secondary to sialolithiasis was made. The patient was discharged and later scheduled for a procedure to remove the sialolith which resolved his facial paralysis. CONCLUSIONS: This case emphasizes the need for a comprehensive approach to the differential diagnosis in presentations of facial palsy. It underscores the potential involvement of parotid sialolithiasis, particularly in patients with a history of recurrent parotitis or facial trauma. Prompt recognition of such uncommon presentations can prevent undue interventions, aid in timely appropriate management, and significantly contribute to the patient's recovery and prevention of long-term complications.
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Paralisia de Bell , Toxinas Botulínicas Tipo A , Paralisia Facial , Parotidite , Cálculos das Glândulas Salivares , Acidente Vascular Cerebral , Masculino , Humanos , Pessoa de Meia-Idade , Glândula Parótida/diagnóstico por imagem , Cálculos das Glândulas Salivares/complicações , Parotidite/complicações , Parotidite/diagnóstico , Paralisia Facial/etiologia , Paralisia de Bell/complicações , Acidente Vascular Cerebral/complicaçõesRESUMO
PURPOSE: This paper describes a new surgical procedure with electrical stimulation of the facial nerve for unresolved Bell's palsy and compares the facial nerve recovery with another group who underwent traditional middle cranial fossa decompression. RECENT FINDINGS: All patients with total unilateral facial paralysis had surgery by the senior author 3 months from onset of Bell's Palsy. Surgical decompression was performed in 13 patients between 1992-2012 (Group 1). Surgical exposure with intraoperative electrical stimulation of the facial nerve in the peri-geniculate region was performed in 47 patients between 2012-2022 (Group 2). The facial recovery at 1 month and 3 month were significantly better in Group 2. The degree of synkinesis was significantly less in Group 2. The trans-mastoid electrical stimulation of the facial nerve is less invasive, requires no hospital stay, and less time off work compared to the middle cranial fossa approach. The earlier facial movement at one month results in less long-term unwanted faulty regeneration or synkinesis.
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Recurrent episodes of weakness in periodic paralysis are caused by intermittent loss of muscle fibre excitability, as a consequence of sustained depolarization of the resting potential. Repolarization is favoured by increasing the fibre permeability to potassium. Based on this principle, we tested the efficacy of retigabine, a potassium channel opener, to suppress the loss of force induced by a low-K+ challenge in hypokalaemic periodic paralysis (HypoPP). Retigabine can prevent the episodic loss of force in HypoPP. Knock-in mutant mouse models of HypoPP (Cacna1s p.R528H and Scn4a p.R669H) were used to determine whether pre-treatment with retigabine prevented the loss of force, or post-treatment hastened recovery of force for a low-K+ challenge in an ex vivo contraction assay. Retigabine completely prevents the loss of force induced by a 2 mM K+ challenge (protection) in our mouse models of HypoPP, with 50% inhibitory concentrations of 0.8 ± 0.13 µM and 2.2 ± 0.42 µM for NaV1.4-R669H and CaV1.1-R528H, respectively. In comparison, the effective concentration for the KATP channel opener pinacidil was 10-fold higher. Application of retigabine also reversed the loss of force (rescue) for HypoPP muscle maintained in 2 mM K+. Our findings show that retigabine, a selective agonist of the KV7 family of potassium channels, is effective for the prevention of low-K+ induced attacks of weakness and to enhance recovery from an ongoing loss of force in mouse models of type 1 (Cacna1s) and type 2 (Scn4a) HypoPP. Substantial protection from the loss of force occurred in the low micromolar range, well within the therapeutic window for retigabine.
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Paralisia Periódica Hipopotassêmica , Camundongos , Animais , Músculo Esquelético , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Fenilenodiaminas/farmacologia , Fenilenodiaminas/uso terapêuticoRESUMO
BACKGROUND: Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell's palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell's palsy. METHODS: This nationwide propensity score-weighting cohort study utilized Taiwan National Health Insurance data. 44,198 patients with DD were identified as the DD cohort and 1,433,650 adult subjects without DD were identified as the comparison cohort. The inverse probability of treatment weighting (IPTW) strategy was used to balance the differences of covariates between two groups. The 5-year incidence of Bell's palsy was evaluated using the Cox proportional-hazard model, presenting results in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The average age of DD patients was 48.3 ± 17.3 years, and 61.86% were female. After propensity score-weighting strategy, no significant demographic differences emerged between the DD and comparison cohort. The Cox proportional hazards model revealed a statistically significant adjusted IPTW-HR of 1.315 (95% CI: 1.168-1.481) for Bell's palsy in DD patients compared to comparison subjects. Further independent factors for Bell's palsy in this model were age (IPTW-HR: 1.012, 95% CI: 1.010-1.013, p < 0.0001), sex (IPTW-HR: 0.909, 95% CI: 0.869-0.952, p < 0.0001), hypertension (IPTW-HR: 1.268, 95% CI: 1.186-1.355, p < 0.0001), hyperlipidemia (IPTW-HR: 1.084, 95% CI: 1.001-1.173, p = 0.047), and diabetes (IPTW-HR: 1.513, 95% CI: 1.398-1.637, p < 0.0001) CONCLUSION: This Study confirmed that individuals with DD face an elevated risk of developing Bell's palsy. These findings hold significant implications for both clinicians and researchers, shedding light on the potential interplay between mental health and the risk of certain physical health outcomes.
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Paralisia de Bell , Transtorno Depressivo , Adulto , Humanos , Feminino , Masculino , Paralisia de Bell/epidemiologia , Paralisia de Bell/etiologia , Paralisia de Bell/psicologia , Pontuação de Propensão , Estudos de Coortes , Modelos de Riscos ProporcionaisRESUMO
Patients with familial hypokalemic periodic paralysis (HOKPP) experience episodes of reversible immobility and are at an increased risk of limited sunlight exposure, potentially leading to vitamin D deficiency. However, there is a lack of data on vitamin D levels in this population. We investigated serum vitamin D levels and their associated factors in children with HOKPP. This study included 170 genetically-confirmed children with HOKPP, aged 3-18 years, and 170 age-, sex-, and body mass index (BMI)-matched healthy controls from the Korean Channelopathy Study, a prospective controlled investigation. Anthropometric and clinical characteristics were recorded, and serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, and intact parathyroid hormone (PTH) were analyzed. Vitamin D deficiency (< 20 ng/mL) was observed in 87.0% of the patients compared to 45.5% of the controls (P < 0.05) during the summer-fall season. During the winter-spring season, 91.7% of the patients and 73.4% of the controls were deficient (P < 0.05). A strong positive correlation was found between onset age of the first paralytic attack and vitamin D levels (r = 0.78, P < 0.01). Conversely, the frequency and duration of paralytic attacks were negatively correlated with vitamin D levels (r = -0.82 and r = -0.65, P < 0.01, respectively). Age, BMI, age at onset, frequency and duration of attacks, and PTH levels were independently associated with vitamin D levels (ß = -0.10, -0.12, 0.19, -0.27, -0.21, and -0.13, P < 0.05, respectively). CONCLUSIONS: Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics. We recommend routine screening for vitamin D levels in these patients to address this prevalent deficiency. Considering the high prevalence of vitamin D deficiency observed, further research on other diseases characterized by reversible immobility is warranted. WHAT IS KNOWN: ⢠A correlation between immobility and low serum vitamin D levels has been established. However, the vitamin D status of patients with familial hypokalemic periodic paralysis (HOKPP) who experience periods of reversible immobility remains unknown. WHAT IS NEW: ⢠Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics.
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Paralisia Periódica Hipopotassêmica , Deficiência de Vitamina D , Criança , Humanos , Adolescente , Cálcio , Paralisia Periódica Hipopotassêmica/etiologia , Paralisia Periódica Hipopotassêmica/complicações , Estudos Prospectivos , Prevalência , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Fatores de Risco , Vitaminas , Hormônio Paratireóideo , Estações do AnoRESUMO
BACKGROUND: Giant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases. CASE PRESENTATION: In this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml. CONCLUSIONS: GOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.
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Adenocarcinoma Mucinoso , Neoplasias Ovarianas , Humanos , Feminino , Adulto , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/diagnóstico , Adenocarcinoma Mucinoso/complicações , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/diagnóstico , Assistência Perioperatória/métodos , Cistos Ovarianos/cirurgia , Cistos Ovarianos/complicações , Cistos Ovarianos/diagnóstico , Estadiamento de NeoplasiasRESUMO
PURPOSE: The anatomical variations of the recurrent laryngeal nerve (RLN) are common during thyroidectomy. We aimed to evaluate the risk of RLN paralysis in case of its anatomical variations, retrospectively. METHODS: The patients with primary thyroidectomy between January 2016 and December 2019 were enrolled. The effect of age, gender, surgical intervention, neuromonitorisation type, central neck dissection, postoperative diagnosis, neck side, extralaryngeal branching, non-RLN, relation of RLN to inferior thyroid artery (ITA), grade of Zuckerkandl tubercle on vocal cord paralysis (VCP) were investigated. RESULTS: This study enrolled 1070 neck sides. The extralaryngeal branching rate was 35.5%. 45.9% of RLNs were anterior and 44.5% were posterior to the ITA, and 9.6% were crossing between the branches of the ITA. The rate of total VCP was 4.8% (transient:4.5%, permanent: 0.3%). The rates of total and transient VCP were significantly higher in extralaryngeal branching nerves compared to nonbranching nerves (6.8% vs. 3.6%, p = 0.018; 6.8% vs. 3.2%, p = 0.006, respectively). Total VCP rates were 7.2%, 2.5%, and 2.9% in case of the RLN crossing anterior, posterior and between the branches of ITA, respectively (p = 0.003). The difference was also significant regarding the transient VCP rates (p = 0.004). Anterior crossing pattern increased the total and transient VCP rates 2.8 and 2.9 times, respectively. CONCLUSION: RLN crossing ITA anteriorly and RLN branching are frequent anatomical variations increasing the risk of VCP in thyroidectomy that cannot be predicted preoperatively. This study is the first one reporting that the relationship between RLN and ITA increased the risk of VCP.
Assuntos
Nervo Laríngeo Recorrente , Glândula Tireoide , Tireoidectomia , Paralisia das Pregas Vocais , Humanos , Tireoidectomia/efeitos adversos , Feminino , Masculino , Paralisia das Pregas Vocais/etiologia , Paralisia das Pregas Vocais/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Glândula Tireoide/irrigação sanguínea , Glândula Tireoide/cirurgia , Glândula Tireoide/inervação , Idoso , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Fatores de Risco , Adulto Jovem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , AdolescenteRESUMO
PURPOSE: Treating an infiltration of the recurrent laryngeal nerve (RLN) by thyroid carcinoma remains a subject of ongoing debate. Therefore, this study aims to provide a novel strategy for intraoperative phenosurgical management of RLN infiltrated by thyroid carcinoma. METHODS: Forty-two patients with thyroid carcinoma infiltrating the RLN were recruited for this study and divided into three groups. Group A comprised six individuals with medullary thyroid cancer who underwent RLN resection and arytenoid adduction. Group B consisted of 29 differentiated thyroid cancer (DTC)patients who underwent RLN resection and ansa cervicalis (ACN)-to-RLN anastomosis. Group C included seven patients whose RLN was preserved. RESULTS: The videostroboscopic analysis and voice assessment collectively indicated substantial improvements in voice quality for patients in Groups A and B one year post-surgery. Additionally, the shaving technique maintained a normal or near-normal voice in Group C one year post-surgery. CONCLUSION: The new intraoperative phonosurgical strategy is as follows: Resection of the affected RLN and arytenoid adduction is required in cases of medullary or anaplastic carcinoma, regardless of preoperative RLN function. Suppose RLN is found infiltrated by well-differentiated thyroid cancer (WDTC) during surgery, and the RLN is preoperatively paralyzed, we recommend performing resection the involved RLN and ACN-to-RLN anastomosis immediately during surgery. If vocal folds exhibit normal mobility preoperatively, the MACIS scoring system is used to assess patient risk stratification. When the MACIS score > 6.99, resection of the involved RLN and immediate ACN-to-RLN anastomosis were performed. RLN preservation was limited to patients with MACIS scores ≤ 6.99.
Assuntos
Nervo Laríngeo Recorrente , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Nervo Laríngeo Recorrente/cirurgia , Tireoidectomia/métodos , Paralisia das Pregas Vocais/etiologia , Paralisia das Pregas Vocais/cirurgia , Idoso , Qualidade da Voz , Invasividade Neoplásica/patologia , Resultado do TratamentoRESUMO
INTRODUCTION: Botulism is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of botulism, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Botulism is a neuromuscular disorder caused by toxin production of clostridium species bacteria and is a challenging diagnosis that mimics several other conditions. Children account for the majority of patients, with a foodborne source most common, followed by wound sources, typically from intravenous drug injection. Classically, patients with botulism develop bilateral cranial nerve palsies and symmetric, bilateral, descending paralysis. However, patients may initially present with vague symptomatology, such as weakness and dry mouth, which can make diagnosis challenging. A careful history elucidating exposures such as intravenous drug use or consumption of non-commercial canned products can help differentiate botulism from other disorders causing neuromuscular weakness. If suspected, the Centers for Disease Control should be notified to mobilize antitoxin for treatment as soon as the diagnosis is suspected even prior to confirmatory testing. Antibiotics should be avoided in these patients, as they can potentiate toxin release, unless there is a concomitant infection requiring antibiotic therapy. Patients with botulism can develop respiratory compromise requiring emergent airway management. Prolonged neuromuscular blockade from botulism will lead to a variety of symptoms that require comprehensive intensive care unit level care. CONCLUSION: An understanding of botulism and its many potential mimics can assist emergency clinicians in diagnosing and managing this deadly disease.
Assuntos
Botulismo , Botulismo/diagnóstico , Botulismo/epidemiologia , Botulismo/terapia , Humanos , Serviço Hospitalar de Emergência , Prevalência , Diagnóstico DiferencialRESUMO
BACKGROUND: Diaphragmatic paralysis can present with orthopnea. We report a unique presentation of bilateral diaphragmatic paralysis, an uncommon diagnosis secondary to an unusual cause, brachial plexitis. This report thoroughly describes the patient's presentation, workup, management, and outcome. It also reviews the literature on diaphragmatic paralysis and Parsonage-Turner syndrome. CASE PRESENTATION: A 50-year-old male patient developed insidious orthopnea associated with left shoulder and neck pain over three months with no associated symptoms. On examination, marked dyspnea was observed when the patient was asked to lie down; breath sounds were present and symmetrical, and the neurological examination was normal. The chest radiograph showed an elevated right hemidiaphragm. Echocardiogram was normal. There was a 63% positional reduction in Forced Vital Capacity and maximal inspiratory and expiratory pressures on pulmonary function testing. The electromyogram was consistent with neuromuscular weakness involving both brachial plexus and diaphragmatic muscle (Parsonage and Turner syndrome). CONCLUSIONS: Compared to unilateral, bilateral diaphragmatic paralysis may be more challenging to diagnose. On PFT, reduced maximal respiratory pressures, especially the maximal inspiratory pressure, are suggestive. Parsonage-Turner syndrome is rare, usually with unilateral diaphragmatic paralysis, but bilateral cases have been reported.