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INTRODUCTION/AIMS: There are no blood biomarkers to monitor treatment effects in myasthenia gravis (MG) or studies visualizing the acetylcholine receptor (AChR) antibody-induced membrane attack complex (MAC) at the human muscle membrane. This study aimed to compare levels of complement activation products and native complement components in MG patients and healthy controls (HCs) and to model the AChR antibody-mediated attacks in human muscle cells. METHODS: We assessed the complement components and activation product levels with enzyme-linked immunosorbent assay and magnetic bead-based sandwich assays in plasma and sera of 23 MG patients and matched HCs. Receiver operator characteristic (ROC) curve analysis evaluated the diagnostic accuracy. Complement levels were correlated with the myasthenia gravis composite (MGC) scores. AChR+ MG modeling in human muscle cells used sera from nine MG patients and three HCs. RESULTS: MG patients had significantly higher plasma levels of C3a (p < .0001), C5 (p = .0003), and soluble C5b-9 (sC5b-9; p < .0001) than HCs. The ROC curve analysis showed a clear separation between MG patients and HCs for plasma C3a (AUC = 0.9720; p < .0001) and sC5b-9 (AUC = 0.8917, p < .0001). MG patients had higher levels of plasma complement Factor I (FI; p = .0002) and lower properdin levels (p < .0001). The MGC had moderate correlations with plasma Factor B (FB), FI, and Factor H. AChR+ MG patient sera triggered the deposition of MAC and reduced AChRs. DISCUSSION: We suggest validating plasma C3a and sC5b-9 as blood biomarkers for complement activation in MG. Further, the in vitro study allowed visualization of MAC deposition after applying AChR+ MG sera on human muscle cells.
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INTRODUCTION/AIMS: The circulating microRNAs (miRNAs) miR-150-5p, miR-30e-5p, and miR-21-5p have been suggested as potential biomarkers for myasthenia gravis (MG); however, the relationships between short-term natural changes of the miRNAs and patient-reported MG outcome scores have not been well-studied. We assessed the short-term fluctuations in miRNA levels and patient-reported outcome measures in MG. METHODS: This prospective cohort study included 39 MG patients with regular follow-ups and unchanged medications at the Neurology outpatient clinic at Uppsala University Hospital. Patients had weekly follow-up visits for 1 month, at which blood samples were drawn, and scores from MG activities of daily living (MG-ADL), MG quality-of-life-15 (MG-QoL15), and Fatigue Severity Scale (FSS) were assessed. Serum levels of miRNA miR-150-5p, miR-30e-5p, and miR-21-5p were analyzed using quantitative real-time PCR. RESULTS: Intra-individual levels of miR-30e-5p and miR-150-5p were stable, whereas a significant reduction in miR-21-5p was observed from week 1 to week 2 (p = .0024) and from week 2 to week 3 (p < .0001). There were intra-individual differences over a short time in MG-ADL, with higher scores in female patients (p = .0281) and a significant reduction from the first to the second weeks (p = .0281), whereas MG-QoL15 and FSS scores were stable. DISCUSSION: The suggested MG biomarkers miR-30e-5p and miR-150-5p were more stable than miR-21-5p over a short time, indicating their short-term stability as biomarkers. Prospective multi-center studies with longer periods of follow-up and matched controls are needed to validate these miRNAs as biomarkers in MG.
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MicroRNAs , Miastenia Gravis , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Miastenia Gravis/sangue , Miastenia Gravis/genética , Feminino , MicroRNAs/sangue , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Estudos Prospectivos , Atividades Cotidianas , Biomarcadores/sangue , Estudos de Coortes , SeguimentosRESUMO
BACKGROUND AND PURPOSE: Few large-scale studies examine whether maternal myasthenia gravis (MG) is a risk factor for complications during pregnancy and childbirth. This study evaluated whether maternal MG is associated with an increased risk of adverse pregnancy, delivery, and neonatal outcomes. METHODS: We conducted a nationwide Swedish register-based cohort study of women who gave birth to singleton infants (≥22 gestational weeks) during 1987-2019. Exposed women were diagnosed with MG before or during the index pregnancy (N = 443). Unexposed women comprised 4249 women without a diagnosis of MG, matched for age, parity, hospital, and year of childbirth. The risks of adverse pregnancy, delivery, and neonatal outcomes for women with MG were estimated using regression modeling and presented as adjusted odds ratios (aOR). RESULTS: There was no increased risk of pregnancy complications in women with MG. Women with MG had a spontaneous onset of labor less often than women without MG (69.8% vs. 79.5%; aOR 0.59; p < 0.001) as well as higher labor induction rates and elective cesarean section deliveries (16.0% vs. 12.3%, aOR 1.42; p = 0.02 and 12.0% vs. 8.1%, aOR 1.59; p = 0.009). Infants of women with MG were born on average 2 days earlier (p = 0.002); however, these infants did not have a higher risk of having low APGAR, being small for gestational age, or having a congenital malformation. CONCLUSION: This first nationwide study of pregnancy in women with MG in Sweden demonstrates reassuring results overall, suggesting generally safe pregnancy outcomes for women with MG and their infants.
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Miastenia Gravis , Resultado da Gravidez , Lactente , Gravidez , Recém-Nascido , Feminino , Humanos , Masculino , Resultado da Gravidez/epidemiologia , Cesárea , Estudos de Coortes , Fatores de Risco , Miastenia Gravis/epidemiologiaRESUMO
BACKGROUND: Generalized myasthenia gravis (MG) with antibodies against the acetylcholine receptor is a chronic disease causing muscle weakness. Access to novel treatments warrants authoritative treatment recommendations. The Nordic countries have similar, comprehensive health systems, mandatory health registers, and extensive MG research. METHODS: MG experts and patient representatives from the five Nordic countries formed a working group to prepare treatment guidance for MG based on a systematic literature search and consensus meetings. RESULTS: Pyridostigmine represents the first-line symptomatic treatment, while ambenonium and beta adrenergic agonists are second-line options. Early thymectomy should be undertaken if a thymoma, and in non-thymoma patients up to the age of 50-65 years if not obtaining remission on symptomatic treatment. Most patients need immunosuppressive drug treatment. Combining corticosteroids at the lowest possible dose with azathioprine is recommended, rituximab being an alternative first-line option. Mycophenolate, methotrexate, and tacrolimus represent second-line immunosuppression. Plasma exchange and intravenous immunoglobulin are used for myasthenic crises and acute exacerbations. Novel complement inhibitors and FcRn blockers are effective and fast-acting treatments with promising safety profiles. Their use depends on local availability, refunding policies, and cost-benefit analyses. Adapted physical training is recommended. Planning of pregnancies with optimal treatment, information, and awareness of neonatal MG is necessary. Social support and adaptation of work and daily life activities are recommended. CONCLUSIONS: Successful treatment of MG rests on timely combination of different interventions. Due to spontaneous disease fluctuations, comorbidities, and changes in life conditions, regular long-term specialized follow-up is needed. Most patients do reasonably well but there is room for further improvement. Novel treatments are promising, though subject to restricted access due to costs.
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Miastenia Gravis , Receptores Colinérgicos , Humanos , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/terapia , Miastenia Gravis/imunologia , Receptores Colinérgicos/imunologia , Autoanticorpos , Imunossupressores/uso terapêutico , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND AND PURPOSE: Although myasthenia gravis (MG) is recognized as an immunoglobulin G autoantibody-mediated disease, the relationship between autoantibody levels and disease activity in MG is unclear. We sought to evaluate this landscape through systematically assessing the evidence, testing the impact of predefined variables on any relationship, and augmenting with expert opinion. METHODS: In October 2020, a forum of leading clinicians and researchers in neurology from across Europe (Expert Forum for Rare Autoantibodies in Neurology in Myasthenia Gravis) participated in a series of virtual meetings that took place alongside the conduct of a systematic literature review (SLR). RESULTS: Forty-two studies were identified meeting inclusion criteria. Of these, 10 reported some correlation between a patient's autoantibody level and disease severity. Generally, decreased autoantibody levels (acetylcholine receptor, muscle-specific kinase, and titin) were positively and significantly correlated with improvements in disease severity (Quantitative Myasthenia Gravis score, Myasthenia Gravis Composite score, Myasthenia Gravis Activities of Daily Living score, Myasthenia Gravis Foundation of America classification). Given the limited evidence, testing the impact of predefined variables was not feasible. CONCLUSIONS: This first SLR to assess whether a correlation exists between autoantibody levels and disease activity in patients with MG has indicated a potential positive correlation, which could have clinical implications in guiding treatment decisions. However, in light of the limited and variable evidence, we cannot currently recommend routine clinical use of autoantibody level testing in this context. For now, patient's characteristics, clinical disease course, and laboratory data (e.g., autoantibody status, thymus histology) should inform management, alongside patient-reported outcomes. We highlight the need for future studies to reach more definitive conclusions on this relationship.
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Atividades Cotidianas , Miastenia Gravis , Humanos , Miastenia Gravis/terapia , Miastenia Gravis/tratamento farmacológico , Autoanticorpos , Imunoglobulina G , BiomarcadoresRESUMO
BACKGROUND AND PURPOSE: The potentially increased risk of extrathymic cancers in myasthenia gravis (MG) remains uncertain. We present the occurrence of extrathymic cancer diagnoses in different MG subgroups. METHODS: We conducted a nationwide Swedish register-based cohort study, including patients who had their first MG diagnosis or first prescription of acetylcholine esterase inhibitors between the years 2006 and 2018. Timing and subtypes of cancer diagnosis in relation to MG as well as corticosteroid-sparing immunosuppressants (CSISs) were identified from national patient, cancer and drug registers. RESULTS: In the study population of 2812 MG patients, 92 had juvenile MG (3%), 632 had early-onset MG (23%), 1968 had late-onset MG (LOMG; 70%) and 120 patients had thymoma-associated MG (TAMG; 4%). Extrathymic cancers were observed in 630 patients (22.4%). Skin cancer and cancer in the male genital organs were most common (N = 138, respectively), followed by cancers in the female genital organs (N = 103), digestive organs (N = 90) and breast (N = 80). Patients with TAMG (29.2%) and LOMG (28.4%) had the highest occurrence of extrathymic cancer. Cancer frequency was comparable between acetylcholine receptor antibody seropositive and seronegative patients. Two or more CSIS prescriptions significantly increased the frequency of cancer, especially cancers in the digestive organs (p = 0.0026), male genital organs (p = 0.0037) and skin (p < 0.0001). CONCLUSIONS: Most extrathymic cancer types in MG were observed in TAMG and LOMG patients, and there was a clear correlation between CSIS exposure and cancer risk. This study sheds light on extrathymic cancers also in non-thymoma MG.
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Miastenia Gravis , Timoma , Neoplasias do Timo , Estudos de Coortes , Feminino , Humanos , Imunossupressores , Masculino , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/epidemiologia , Receptores Colinérgicos , Suécia/epidemiologiaRESUMO
INTRODUCTION: To reduce myasthenia gravis (MG) patient risk of immunosuppressant (IS) exposure adverse events (AEs), such as infections and malignancies, and to reduce treatment burden, international guidelines recommend decreasing IS dose in stable MG patients. METHODS: Online surveys were conducted of self-identified MG patients and MG physician experts about the importance of IS dose reduction for MG patients who achieve prolonged periods of disease stability. RESULTS: Eighty-four percent of MG patients (n = 283) and 100% of physicians (n = 45) were concerned about long-term IS-associated AEs. Although both groups favored attempting IS reduction, they raised concerns including MG relapse, hospitalization, and uncertainty about the future. Presented with an estimated 12% significant relapse rate with IS dose reduction, 76% of patients would be willing to enroll in a randomized IS dose reduction trial. DISCUSSION: Patients and physicians favor considering IS dose reduction but are also concerned about potential negative sequelae.
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Conhecimentos, Atitudes e Prática em Saúde , Imunossupressores/administração & dosagem , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/psicologia , Participação do Paciente/psicologia , Papel do Médico/psicologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Participação do Paciente/métodos , Inquéritos e QuestionáriosAssuntos
Miastenia Gravis , Complicações na Gravidez , Gravidez , Recém-Nascido , Feminino , Humanos , Miastenia Gravis/complicaçõesRESUMO
PURPOSE: To evaluate disease-specific differences between Myasthenia Gravis (MG) subgroups and compare patterns of lifestyle between MG patients and population controls. METHODS: All MG patients (n = 70) in Jönköping County, Sweden, were invited to answer a disease-specific questionnaire, containing questions about disease-specific data, lifestyle, comorbidity, and mental fatigue. The patients were clinically evaluated. Four hundred age- and gender-matched population controls were invited to answer the nondisease-specific part of the questionnaire. Disease-specific issues were compared between MG subgroups. Lifestyle-related factors and concomitant conditions were compared to the population controls. RESULTS: Forty MG patients and 188 population controls participated in the study. In the late-onset MG (LOMG; N = 18) subgroup, the male predominance was higher than previously reported. In the early-onset MG (EOMG; N = 17) subgroup, time to diagnosis was longer, fatigue was higher, and bulbar weakness was the dominant symptom (65%). Compared to their matched population controls, LOMG patients were more obese (OR = 13.7, P = 0.015), ate less fish (OR = 4.1, P = 0.012), tended to smoke more (OR = 4.1, P = 0.086), and tended to be employed as manual laborers more often (OR = 2.82, P = 0.083). Mental health problems and sickness benefits were more common among MG patients than in controls, and MG patients were less regularly doing focused physical activity. CONCLUSIONS: It is important to consider disease-specific differences when tailoring the management of individual MG patients. There is a need for improved knowledge on how to apply primary and secondary prevention measures to lifestyle disorders in MG patients without risk of deterioration.
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Estilo de Vida , Miastenia Gravis , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SuéciaRESUMO
INTRODUCTION: Due to the shortage of exercise-related research in Myasthenia Gravis (MG), there are no consensus guidelines on physical exercise for MG patients. METHODS: In this prospective pilot study, 10 MG patients with mild disease performed supervised aerobic and resistance training twice weekly for 12 weeks. The Myasthenia Gravis Composite (MGC) score, compound motor action potential (CMAP), repetitive nerve stimulation, muscle force, physical performance-based measures, serum levels of interleukin-6, muscle enzymes, and immuno-microRNAs miR-150-5p and miR-21-5p were assessed before and after the training period. RESULTS: Physical exercise was well tolerated, and the MGC score was unchanged. Muscle resistance weights and CMAP amplitudes increased for biceps brachii and rectus femoris muscles, and physical performance-based measures improved. Muscle enzymes remained normal, whereas disease-specific microRNAs miR-150-5p and miR-21-5p were reduced after the training period. CONCLUSIONS: We propose that general recommendations regarding physical exercise can be applied safely to well-regulated MG patients. Muscle Nerve 56: 207-214, 2017.
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Exercício Físico/fisiologia , Miastenia Gravis/fisiopatologia , Miastenia Gravis/reabilitação , Junção Neuromuscular/fisiologia , Treinamento Resistido/métodos , Idoso , Idoso de 80 Anos ou mais , Composição Corporal/fisiologia , Potencial Evocado Motor/fisiologia , Feminino , Seguimentos , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Dinamômetro de Força Muscular , Condução Nervosa/fisiologia , Junção Neuromuscular/fisiopatologia , Projetos Piloto , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Different volumes of 0.9% NaCl may be used to reconstitute abobotulinumtoxinA yielding an injection volume that ranges from 0.05 to 0.1 mL per injection point for treatment of glabellar lines. OBJECTIVE: To evaluate the efficacy, safety, and subject satisfaction of 2 different injection volumes to deliver the same unit dose of abobotulinumtoxinA for treatment of glabellar lines. MATERIALS AND METHODS: This randomized comparative study was conducted using 2 different reconstitution volumes to deliver a fixed unit dose of 10 Speywood units (sU) of abobotulinumtoxinA in either 0.05 mL (labeled volume) or 0.1 mL (twofold volume) per injection point. Evaluations included wrinkle severity, neurophysiological assessment by compound muscle action potential (CMAP), and subject satisfaction. RESULTS: Use of either injection volume of abobotulinumtoxinA resulted in the early onset of effect, high effectiveness, and long duration of effect. The safety profile and injection pain levels were similar in both groups. The twofold injection volume was shown to be noninferior to the labeled injection volume based on CMAP results. CONCLUSION: A twofold increase in injection volume to 0.1 mL per injection point to deliver 10 sU of abobotulinumtoxinA is effective and safe.
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Inibidores da Liberação da Acetilcolina/administração & dosagem , Toxinas Botulínicas Tipo A/administração & dosagem , Músculo Esquelético/efeitos dos fármacos , Satisfação do Paciente , Envelhecimento da Pele/efeitos dos fármacos , Inibidores da Liberação da Acetilcolina/efeitos adversos , Potenciais de Ação , Adulto , Toxinas Botulínicas Tipo A/efeitos adversos , Feminino , Testa , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Dor/etiologiaRESUMO
Despite the extensive use of botulinum toxin A (BoNTA) in medical and cosmetic treatments, the potential spreading of BoNTA to surrounding tissues remains unknown. A patient with hemifacial paralysis upon blepharospasm treatment with low dose of BoNTA, prompted us to investigate the spreading effect. A randomised, double-blind study was conducted in which 5 healthy women (33-52 years) were treated with different doses of onabotulinum toxin unilaterally in the corrugator muscle. Parameters of efficacy and diffusion (CMAP; EMG and jitter analysis) in both glabellar and frontalis muscles were assessed at baseline, 2 and 4 weeks following BoNTA injection. CMAP of the treated glabellar muscles was reduced to approximately 40% in all dose groups. Additionally, contralateral CMAP reduction was observed in 3 of 5 subjects. These data confirm regional diffusion of BoNTA in facial muscle application, which raises question on the reliability of split-face models in BoNTA studies.
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Inibidores da Liberação da Acetilcolina/farmacocinética , Toxinas Botulínicas Tipo A/farmacocinética , Músculos Faciais/metabolismo , Inibidores da Liberação da Acetilcolina/administração & dosagem , Inibidores da Liberação da Acetilcolina/efeitos adversos , Potenciais de Ação/efeitos dos fármacos , Adulto , Idoso de 80 Anos ou mais , Blefarospasmo/tratamento farmacológico , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Ensaios Clínicos Controlados como Assunto/métodos , Difusão , Método Duplo-Cego , Eletromiografia , Músculos Faciais/efeitos dos fármacos , Paralisia Facial/induzido quimicamente , Feminino , Testa , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Projetos de PesquisaRESUMO
Despite the extensive use of botulinum toxin type A (BoNT-A) in treatments for glabellar frown lines, the dose-response effect in the glabellar muscles remains unknown. The aim of this randomized, double-blind, placebo-controlled prospective study was to characterize the neurophysiological parameters that correlate with the effect of BoNT-A in the glabellar muscles and its diffusion to surrounding ocular muscles. Sixteen healthy women were recruited and randomized to 3 different dose-groups of onabotulinumtoxin A (Vistabel®) or placebo and followed 24 weeks by neuro-physiological examinations. Efficacy of treatment on corrugator supercilii muscles was measured by compound motor action potential (CMAP) and electromyography (EMG). Photographs were used to score glabellar frown lines. Diffusion of the drug to surrounding muscles was assessed by CMAP of the nasalis muscle, EMG and concentric needle electrode jitter analysis (CNE) of the orbicularis oculi muscle. CMAP reduction correlated well with intramuscular BoNT-A dose. Muscle paralysis, measured by EMG, began from 2 weeks and was not entirely reversed at 24 weeks in individuals who received high dose of onabotulinumtoxin. Limited diffusion of orbicularis oculi was detected with CNE. In conclusion, we developed a novel neurophysiological strategy for effect evaluation of BoNT-A in glabellar muscles. CMAP and EMG correlated with given BoNT-A dose and are more defined effect measures than clinical glabellar photo scales.
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Toxinas Botulínicas Tipo A/administração & dosagem , Músculos Faciais/efeitos dos fármacos , Fármacos Neuromusculares/administração & dosagem , Potenciais de Ação , Adulto , Toxinas Botulínicas Tipo A/efeitos adversos , Técnicas Cosméticas , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eletromiografia , Músculos Faciais/fisiologia , Feminino , Humanos , Injeções Intramusculares , Pessoa de Meia-Idade , Fenômenos Fisiológicos Oculares/efeitos dos fármacos , Fotografação , Estudos Prospectivos , Envelhecimento da Pele/efeitos dos fármacosRESUMO
OBJECTIVE: This study aimed to explore the clinical characteristics and temporal disease course of patients with autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS) in Sweden. METHODS: Thirty-seven antibody-positive AE and PNS cases were identified in the Healthcare region Mid Sweden between 2015 and 2019. Clinical data were collected through a retrospective review of electronic health records. Patients were divided into three subgroups based on antibody type: neuronal surface antibodies (NSAbs), onconeural antibodies, and anti-GAD65 antibodies. RESULTS: Nineteen patients had NSAbs, 11 onconeural antibodies, and seven anti-GAD65 antibodies. Anti-LGI1 and anti-NMDAR were the most frequently detected NSAbs, with anti-NMDAR cases having an older-than-expected age distribution (median age 40, range 17-72). Only 11 of 32 (30%) of patients had findings suggesting encephalitis on initial MRI, but 28 of 31 (90%) had pathological findings on initial cerebrospinal fluid analysis. All patients but one had abnormal EEG findings. Median time to immunotherapy was comparable among the three subgroups, whereas patients with anti-LGI1, anti-CASPR2, and anti-IgLON5 had an eightfold longer time to immunotherapy than anti-NMDAR and anti-GABA-B (p = .0016). There was a seasonal variation in onset for patients with non-tumor-related NSAbs and anti-GAD65 antibodies, with most patients (72%) falling ill in spring or summer. CONCLUSION: Swedish patients with AE and PNS had similar clinical characteristics as previously described cohorts from other geographical regions except for anti-NMDAR encephalitis, with older onset than expected. The onset of non-tumor-related AE occurred predominantly in the warm seasons, and AE with a more insidious onset was associated with delayed treatment initiation.
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Autoanticorpos , Encefalite , Doença de Hashimoto , Síndromes Paraneoplásicas do Sistema Nervoso , Humanos , Suécia/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/fisiopatologia , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Encefalite/imunologia , Estudos Retrospectivos , Adulto Jovem , Adolescente , Doença de Hashimoto/imunologia , Glutamato Descarboxilase/imunologiaRESUMO
There is an unmet need for objective disease-specific biomarkers in the heterogeneous autoimmune neuromuscular disorder myasthenia gravis (MG). This cross-sectional study identified a signature of 23 inflammatory serum proteins with proximity extension assay (PEA) that distinguishes acetylcholine receptor antibody seropositive (AChR+) MG patients from healthy controls (HCs). CCL28, TNFSF14, 4E-BP1, transforming growth factor alpha (TGF-α), and ST1A1 ranked top biomarkers. TGF-ß1 and osteoprotegerin (OPG) differed between early- and late-onset MG, whereas CXCL10, TNFSF14, CCL11, interleukin-17C (IL-17C), and TGF-α differed significantly with immunosuppressive treatment. MG patients with moderate to high disease severity had lower uPA. Previously defined MG-associated microRNAs, miR-150-5p, miR-30e-5p, and miR-21-5p, correlated inversely with ST1A1 and TNFSF14. The presented inflammatory proteins that distinguish AChR+ MG are promising serum biomarkers for validation in prospective studies to allow for molecular signatures for patient subgroup stratification and monitoring of treatment response.
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Mammalian axons are specialized for transmitting action potentials to targets within the central and peripheral nervous system. A growing body of evidence suggests that, besides signal conduction, axons play essential roles in neural information processing, and their malfunctions are common hallmarks of neurodegenerative diseases. The technologies available to study axonal function and structure integrally limit the comprehension of axon neurobiology. High-density microelectrode arrays (HD-MEAs) allow for accessing axonal action potentials at high spatiotemporal resolution, but provide no insights on axonal morphology. Here, we demonstrate a method for electrical visualization of axonal morphologies based on extracellular action potentials recorded from cortical and motor neurons using HD-MEAs. The method enabled us to reconstruct up to 5-cm-long axonal arbors and directly monitor axonal conduction across thousands of recording sites. We reconstructed 1.86 m of cortical and spinal axons in total and found specific features in their structure and function.
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Axônios , Diagnóstico por Imagem , Animais , Potenciais de Ação , Cisteamina , Eletricidade , MamíferosRESUMO
Aesthetic use of low doses of Botulinum toxin (BoNT) injections into the facial muscles has become a leading non-surgical aesthetic treatment worldwide to reduce facial wrinkles, including glabellar lines, forehead lines, and periorbital wrinkles. Within these aesthetic applications, BoNT injections intend to reduce and prevent wrinkles, and the recommended usage of 2â¯years is often exceeded, which may result in atrophy of the injected muscles. The long-term effects of BoNT injections in the facial muscles and the evidence of diffusion of BoNT to surrounding muscles are obvious pitfalls and challenges for clinical neurophysiologists in differential diagnosing neuromuscular transmission failures. Also, this is further complicated by the risk of developing side effects upon permanent chemical denervation of facial muscles, with less possibility for reinnervation. This review summarizes the known long-term effects of BoNT over time in different facial muscles and the use of objective electrophysiological measures to evaluate these. A better understanding of the long-term effects of BoNT is essential to avoid misdiagnosing other neuromuscular disorders.
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Although supervised aerobic and resistance training in a hospital setting was proven safe and beneficial for well-controlled myasthenia gravis (MG) patients, implementation of similar programs in the community has not been studied. We conducted a pragmatic open-label study at a large gym in Uppsala, Sweden. Seven patients with generalized MG were recruited to participate in an individualized, tailored exercise program, based on individual baseline status and personal goals, with a personal trainer. All patients completed the entire training period. The individually tailored exercise program was implemented safely and effectively, with all patients improving in aerobic capacity, muscle strength, and balance. Our pragmatic open-label case study suggests that well-controlled patients with generalized MG can extend their physical exercise to personal training in the gym. This is an essential step towards reducing the barriers to implementing exercise procols and increasing the availability of these interventions to MG patients.
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Miastenia Gravis , Treinamento Resistido , Humanos , Terapia por Exercício , Estudos de Viabilidade , Exercício Físico/fisiologiaRESUMO
INTRODUCTION: Repeater F-waves are sometimes seen in routine studies. METHODS: We retrospectively reviewed the clinical significance of repeater F-waves in median, ulnar, and fibular nerve recordings in 50 healthy subjects and groups of 50 patients each with diabetic polyneuropathy, amyotrophic lateral sclerosis, carpal tunnel syndrome, ulnar mononeuropathy, and L5 root lesion. The number of identical F-waves and their repetitions in samples of 20 stimuli were estimated. RESULTS: Repeater F-waves occurred significantly more frequently in all nerves and patient groups than in healthy individuals. Their persistence was negatively correlated with that of non-repeater F-waves. CONCLUSIONS: Based on the presented material and recording condition it appears that repeater F-waves differentiate between health and disease but not between different types of pathology of motor neurons or their axons. Even in routinely recorded samples of 20 traces, the index of repeater all F-waves could be used as a sign of nerve pathology.