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1.
Epilepsia ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554037

RESUMO

OBJECTIVE: This study was undertaken to characterize the use of higher doses of folic acid (≥1 mg daily) in relation to pregnancy in Denmark, Norway, and Sweden in women with epilepsy treated with antiseizure medication (ASM). METHODS: In this observational study, we used data from national medical birth, patient, and prescription registers in Denmark, Norway, and Sweden to retrospectively identify pregnancies in women with epilepsy treated with ASM from 2006 to 2017. The proportion of higher dose folic acid supplementation in pregnancies among women receiving ASM for epilepsy was calculated according to country of origin, time period, and type of ASM. Logistic regression with restricted cubic splines was used to model country-specific time trends. RESULTS: Among a total of 2 748 882 pregnancies, we identified 8695 (.3%) pregnancies after restricting the population to women with ASM-treated epilepsy. A prescription for higher dose folic acid was filled in 4719 (54.3%) of these pregnancies. The proportion supplemented with higher dose folic acid was highest in Sweden (74.3%) and lower in Norway (41.4%) and Denmark (34.3%). Furthermore, we observed a decreasing trend of higher dose folic acid use in Denmark and Norway from year 2012 to 2017. Among those who used higher dose folic acid, 42% did not start preconception supplementation with higher dose folic acid. SIGNIFICANCE: Supplementation with higher dose folic acid occurred in approximately half of pregnancies in women with ASM-treated epilepsy, with many not starting supplementation until after becoming pregnant. Considerable variability was observed in the use of higher dose folic acid across the countries, despite similar population characteristics and health care systems. Future guidelines should be simplified with clear recommendations developed in a collaborative manner by relevant specialists including neurologists, obstetricians, pediatricians, and public health specialists to enhance real-world applicability.

2.
Lancet Reg Health Eur ; 38: 100849, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38476755

RESUMO

Background: The short- and long-term consequences of restricted fetal growth cause considerable concern, and how prenatal exposure to different antiseizure medications (ASMs) affects fetal growth remains uncertain. Methods: This was a population-based cohort study of liveborn singleton children born in Denmark, Finland, Iceland, Norway, and Sweden from 1996 to 2017. Prenatal exposure was defined as maternal filling of prescriptions for ASM during pregnancy registered in national prescription registries and primary outcomes were adjusted odds ratios (aORs) of microcephaly or being born small for gestational age. Findings: We identified 4,494,918 children (males: 51.3%, 2,306,991/4,494,918), including 38,714 (0.9%) children of mothers with epilepsy. In the overall population, prenatal monotherapy exposure with carbamazepine (aOR: 1.25 (95% CI: 1.12-1.40)), pregabalin (aOR: 1.16 (95% CI: 1.02-1.31)), oxcarbazepine (aOR: 1.48 (95% CI: 1.28-1.71)), clonazepam (aOR: 1.27 (95% CI: 1.10-1.48)), and topiramate (aOR: 1.48 (95% CI: 1.18-1.85)) was associated with risk of being born small for gestational age, and carbamazepine was associated with microcephaly (aOR: 1.43 (95% CI: 1.17-1.75)). In children of mothers with epilepsy, prenatal exposure to carbamazepine (aOR: 1.27 (95% CI: 1.11-1.47)), oxcarbazepine (aOR: 1.42 (95% CI: 1.18-1.70)), clonazepam (aOR: 1.40 (95% CI: 1.03-1.89)), and topiramate (aOR: 1.86 (95% CI: 1.36-2.54)) was associated with being born small for gestational age; carbamazepine, with microcephaly (aOR: 1.51 (95% CI: 1.17-1.95)). No associations with small for gestational age and microcephaly were identified after prenatal exposure to lamotrigine, valproate, gabapentin, levetiracetam, phenobarbital, acetazolamide, phenytoin, clobazam, primidone, zonisamide, vigabatrin, ethosuximide and lacosamide, but except for lamotrigine, valproate, gabapentin, and levetiracetam, numbers of exposed children were small. Interpretation: Prenatal exposure to carbamazepine, oxcarbazepine, clonazepam, and topiramate was associated with increased risk of being born small for gestational age in both the overall population and in children of women with epilepsy suggesting that prenatal exposure to these drugs is associated with fetal growth restriction. Funding: The NordForsk Nordic Program on Health and Welfare (83539), the Independent Research Fund Denmark (1133-00026B), the Danish Epilepsy Association, the Central Denmark Region, the Novo Nordisk Foundation (NNF16OC0019126 and NNF22OC0075033), and the Lundbeck Foundation (R400-2022-1205).

3.
Eur J Neurol ; 31(5): e16229, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38321574

RESUMO

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.


Assuntos
Miastenia Gravis , Doenças Neuromusculares , Neoplasias do Timo , Gravidez , Feminino , Recém-Nascido , Humanos , Pessoa de Meia-Idade , Idoso , Miastenia Gravis/tratamento farmacológico , Receptores Colinérgicos , Brometo de Piridostigmina/uso terapêutico , Imunossupressores/uso terapêutico , Autoanticorpos , Timectomia
4.
Eur J Neurol ; 31(5): e16233, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38323756

RESUMO

BACKGROUND AND PURPOSE: With the emergence of new treatment options for myasthenia gravis (MG), there is a need for information regarding epidemiology, healthcare utilization, and societal costs to support economic evaluation and identify eligible patients. We aimed to enhance the understanding of these factors using nationwide systematic registry data in Norway. METHODS: We received comprehensive national registry data from five Norwegian health- and work-related registries. The annual incidence and prevalence were estimated for the period 2013-2021 using nationwide hospital and prescription data. The direct, indirect (productivity losses) and intangible costs (value of lost life-years [LLY] and health-related quality of life [HRQoL]) related to MG were estimated over a period of 1 year. RESULTS: In 2021, the incidence of MG ranged from 15 to 16 cases per year per million population depending on the registry used, while the prevalence varied between 208.9 and 210.3 per million population. The total annual societal costs of MG amounted to EUR 24,743 per patient, of which EUR 3592 (14.5%) were direct costs, EUR 8666 (35.0%) were productivity loss, and EUR 12,485 (50.5%) were lost value from LLY and reduced HRQoL. CONCLUSION: The incidence and prevalence of MG are higher than previously estimated, and the total societal costs of MG are substantial. Our findings demonstrate that productivity losses, and the value of LLY and HRQoL constitute a considerable proportion of the total societal costs.


Assuntos
Custos de Cuidados de Saúde , Miastenia Gravis , Humanos , Qualidade de Vida , Dados de Saúde Coletados Rotineiramente , Efeitos Psicossociais da Doença , Noruega/epidemiologia , Miastenia Gravis/epidemiologia , Miastenia Gravis/terapia
5.
J Clin Med ; 13(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38398450

RESUMO

Myasthenia gravis (MG) is a rare autoimmune disease. Transient neonatal myasthenia gravis (TNMG) is caused by pathogenic maternal autoantibodies that cross the placenta and disrupt signaling at the neuromuscular junction. This is a systematic review of this transient immunoglobulin G (IgG)-mediated disease. TNMG affects 10-20% of children born to mothers with MG. The severity of symptoms ranges from minor feeding difficulties to life-threatening respiratory weakness. Minor symptoms might go unnoticed but can still interfere with breastfeeding. Acetylcholine-esterase inhibitors and antibody-clearing therapies such as immunoglobulins can be used to treat TNMG, but most children do well with observation only. TNMG is self-limiting within weeks as circulating antibodies are naturally cleared from the blood. In rare cases, TNMG is associated with permanent skeletal malformations or permanent myopathy. The mother's antibodies can also lead to spontaneous abortions. All healthcare professionals meeting pregnant or birthing women with MG or their neonates should be aware of TNMG. TNMG is hard to predict. Reoccurrence is common among siblings. Pre-pregnancy thymectomy and intravenous immunoglobulins during pregnancy reduce the risk. Neonatal fragment crystallizable receptor (FcRn) blocking drugs for MG might reduce TNMG risk.

6.
BMC Neurol ; 24(1): 61, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38336636

RESUMO

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disease characterised by muscle weakness, and progression from ocular (oMG) to generalised (gMG) symptoms results in a substantial negative impact on quality of life (QoL). This systematic review aimed to provide an overview of the patient burden experienced by people living with gMG. METHODS: Electronic database searches (conducted March 2022), supplemented by interrogation of grey literature, were conducted to identify studies reporting patient burden outcomes in patients with gMG in Europe, the Middle East and Africa. Results were synthesised narratively due to the heterogeneity across trials. RESULTS: In total, 39 patient burden publications (representing 38 unique studies) were identified as relevant for inclusion in the systematic review, consisting of 37 publications reporting formal patient-reported outcome measures (PROMs), and two publications describing alternative qualitative assessments of patient experience. The studies included a variety of measures including generic and disease-specific PROMs, as well as symptom-specific PROMs focusing on key comorbidities including depression, anxiety, fatigue and sleep disturbance. The findings showed some variation across studies and PROMs; however, in general there was evidence for worse QoL in patients with gMG than in healthy controls or in patients with oMG, and a trend for worsening QoL with increasing MG severity. CONCLUSIONS: This review highlights the importance of considering patient QoL when developing and assessing treatment and management plans for patients with gMG. However, the heterogeneity identified across studies illustrates the need for further representative and well-powered studies in large cohorts administering consistent, validated questionnaires. TRIAL REGISTRATION: The protocol for this systematic review was registered in PROSPERO: CRD42022328444.


Assuntos
Miastenia Gravis , Qualidade de Vida , Humanos , Miastenia Gravis/epidemiologia , Miastenia Gravis/terapia , Miastenia Gravis/diagnóstico , África , Oriente Médio/epidemiologia , Europa (Continente)/epidemiologia
7.
Int J Mol Sci ; 25(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338799

RESUMO

Adverse childhood experiences (ACEs), such as abuse, neglect, and household dysfunction, contribute to long-term systemic toxic stress and inflammation that may last well into adulthood. Such early-life stressors have been associated with increased susceptibility to multiple sclerosis (MS) in observational studies and with the development of experimental autoimmune encephalomyelitis in animal models. In this review, we summarize the evidence for an ACE-mediated increase in MS risk, as well as the potential mechanisms for this association. ACEs dysregulate neurodevelopment, stress responses, and immune reactivity; they also alter the interplay between the immune system and neural networks. All of this may be relevant for MS risk. We further discuss how ACEs induce epigenetic changes and how the toxic stress caused by ACEs may reactivate the Epstein-Barr Virus (EBV), a key risk factor for MS. We conclude by suggesting new initiatives to obtain further insights into this topic.


Assuntos
Experiências Adversas da Infância , Maus-Tratos Infantis , Infecções por Vírus Epstein-Barr , Esclerose Múltipla , Humanos , Criança , Esclerose Múltipla/etiologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4
8.
9.
Front Neurol ; 14: 1237140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37900608

RESUMO

Objectives: Autoantibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and leucine-rich glioma-inactivated 1 (Lgi1) are associated with autoimmune encephalitis. We described an acetylcholine receptor (AChR)-positive patient with myasthenia gravis who developed limbic encephalitis with antibodies to AMPAR and Lgi1. Methods: A single-case report with detailed, prospective clinical and biomarker data including serial laboratory testing and histopathology. Results: A 49-year-old woman was diagnosed with anti-AChR antibody-positive generalized myasthenia gravis in 1983. After 9 months of the removal of thymoma in 1984, she developed influenza-like symptoms and then symptoms of limbic encephalitis. Retrospective analysis of serum showed high concentrations of anti-AMPAR and lower concentrations of anti-Lgi1 antibodies. Cerebral CT was normal, EEG showed bifrontal dysrhythmia, and CSF showed mild pleocytosis. Immuno-histochemical examination of the thymoma confirmed staining for Glur2, a subunit of AMPAR. The patient recovered with mild sequelae, but low levels of anti-AMPAR and anti-Lgi1 antibodies were detectable for over 25 years subsequently. Discussion: This case confirms earlier reports of AMPAR-associated autoimmune encephalitis co-occurring with thymoma and myasthenia gravis and is unique in its observational length. It shows, moreover, that antibodies to AMPAR and Lgi1 can persist despite clinical recovery.

10.
Handb Clin Neurol ; 195: 635-652, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37562891

RESUMO

Myasthenia gravis is an autoimmune disorder caused by antibodies against elements in the postsynaptic membrane at the neuromuscular junction, which leads to muscle weakness. Congenital myasthenic syndromes are rare and caused by mutations affecting pre- or postsynaptic function at the neuromuscular synapse and resulting in muscle weakness. MG has a prevalence of 150-250 and an annual incidence of 8-10 individuals per million. The majority has disease onset after age 50 years. Juvenile MG with onset in early childhood is more common in East Asia. MG is subgrouped according to type of pathogenic autoantibodies, age of onset, thymus pathology, and generalization of muscle weakness. More than 80% have antibodies against the acetylcholine receptor. The remaining have antibodies against MuSK, LRP4, or postsynaptic membrane antigens not yet identified. A thymoma is present in 10% of MG patients, and more than one-third of thymoma patients develop MG as a paraneoplastic condition. Immunosuppressive drug therapy, thymectomy, and symptomatic drug therapy with acetylcholine esterase inhibitors represent cornerstones in the treatment. The prognosis is good, with the majority of patients having mild or moderate symptoms only. Most congenital myasthenic syndromes are due to dysfunction in the postsynaptic membrane. Symptom debut is in early life. Symptomatic drug treatment has sometimes a positive effect.


Assuntos
Miastenia Gravis , Síndromes Miastênicas Congênitas , Timoma , Neoplasias do Timo , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Síndromes Miastênicas Congênitas/diagnóstico , Síndromes Miastênicas Congênitas/genética , Timoma/complicações , Miastenia Gravis/diagnóstico , Miastenia Gravis/genética , Miastenia Gravis/terapia , Debilidade Muscular/etiologia , Autoanticorpos , Neoplasias do Timo/complicações
11.
Front Neurol ; 14: 1201451, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37521306

RESUMO

Myasthenia gravis (MG) is a disorder of the neuromuscular junction that can deteriorate into myasthenic crisis, involving weakness of bulbar and respiratory muscles. In this study, we describe the clinical manifestations of myasthenic crisis, identify risk factors, and examine treatments and outcomes. All 95 patients with generalized MG treated at our center during the last 10 years were included in this retrospective study. We collected data from the patients' records, including clinical follow-ups, muscle antibodies, thymic status, and treatments. The characteristics of patients who did and did not experience myasthenic crisis were compared. Features of all myasthenic crises were also assessed. Twelve patients (13%) developed myasthenic crisis during the observation period. Men were more often affected at older ages. Seven patients experienced multiple myasthenic crises. Thymoma increased the risk of a crisis, whereas thymic hyperplasia decreased the risk. Myasthenic crises were more common in the summer months. No patients died during a myasthenic crisis. Risk factors for myasthenic crisis were thymoma, older age, MuSK antibodies, and previous crises. Individualized and active immunosuppressive treatment and optimal intensive care during crises provide a good outcome for patients with generalized MG.

12.
Epilepsia ; 64(9): 2244-2248, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37452793

RESUMO

Women using antiseizure medication in pregnancy are often advised to use high doses of folic acid supplements (1mg to 5 mg) to reduce the risk of teratogenicity. Recently, we published a report showing an association between maternal prescription fill of high dose folic acid in relation to pregnancy and childhood cancer in the offspring. The report has sparked a debate about which dose of folic acid that should be recommended in pregnancy in women in need of antiseizure medication. In this Commentary, we explain our findings and the method used in our report, and answer recent questions that have emerged.


Assuntos
Ácido Fólico , Neoplasias , Gravidez , Feminino , Humanos , Criança , Ácido Fólico/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Risco , Família , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Neoplasias/tratamento farmacológico
13.
Front Neurol ; 14: 1165592, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37288067

RESUMO

Purpose: The purpose of this study is to investigate the impact of Bergen Epileptiform Morphology Score (BEMS) and interictal epileptiform discharge (IED) candidate count in EEG classification. Methods: We included 400 consecutive patients from a clinical SCORE EEG database during 2013-2017 who had focal sharp discharges in their EEG, but no previous diagnosis of epilepsy. Three blinded EEG readers marked all IED candidates. BEMS and IED candidate counts were combined to classify EEGs as epileptiform or non-epileptiform. Diagnostic performance was assessed and then validated in an external dataset. Results: Interictal epileptiform discharge (IED) candidate count and BEMS were moderately correlated. The optimal criteria to classify an EEG as epileptiform were either one spike at BEMS > = 58, two at > = 47, or seven at > = 36. These criteria had almost perfect inter-rater reliability (Gwet's AC1 0.96), reasonable sensitivity of 56-64%, and high specificity of 98-99%. The sensitivity was 27-37%, and the specificity was 93-97% for a follow-up diagnosis of epilepsy. In the external dataset, the sensitivity for an epileptiform EEG was 60-70%, and the specificity was 90-93%. Conclusion: Quantified EEG spike morphology (BEMS) and IED candidate count can be combined to classify an EEG as epileptiform with high reliability but with lower sensitivity than regular visual EEG review.

14.
Am J Clin Nutr ; 118(1): 303-313, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37217097

RESUMO

BACKGROUND: Prenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment. OBJECTIVES: To examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy. METHODS: We included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, Father, and Child Cohort Study. Information on ASM use, folic acid supplement use and dose, dietary folate intake, child autistic traits, and child language impairment was obtained from parent-reported questionnaires. Using logistic regression, we examined the interaction between prenatal ASM exposure and maternal genetic liability to folate deficiency expressed as polygenic risk score of low folate concentrations or maternal rs1801133 genotype (CC or CT/TT) on risk of language impairment or autistic traits. RESULTS: We included 96 children of women with ASM-treated epilepsy, 131 children of women with ASM-untreated epilepsy, and 37,249 children of women without epilepsy. The polygenic risk score of low folate concentrations did not interact with the ASM-associated risk of language impairment or autistic traits in ASM-exposed children of women with epilepsy compared with ASM-unexposed children aged 1.5-8 y. ASM-exposed children had increased risk of adverse neurodevelopment regardless of maternal rs1801133 genotype {adjusted odds ratio [aOR] for language impairment aged 8 y was 2.88 [95% confidence interval (CI): 1.00, 8.26] if CC and aOR 2.88 [95% CI: 1.10, 7.53] if CT/TT genotypes}. In children of women without epilepsy aged 3 y, those with maternal rs1801133 CT/TT compared with CC genotype had increased risk of language impairment (aOR: 1.18; 95% CI: 1.05, 1.34). CONCLUSIONS: In this cohort of pregnant women reporting widespread use of folic acid supplements, maternal genetic liability to folate deficiency did not significantly influence the ASM-associated risk of impaired neurodevelopment.


Assuntos
Transtorno Autístico , Epilepsia , Deficiência de Ácido Fólico , Transtornos do Desenvolvimento da Linguagem , Efeitos Tardios da Exposição Pré-Natal , Humanos , Criança , Feminino , Gravidez , Estudos de Coortes , Transtorno Autístico/genética , Transtorno Autístico/tratamento farmacológico , Ácido Fólico , Epilepsia/tratamento farmacológico , Epilepsia/genética , Deficiência de Ácido Fólico/complicações , Deficiência de Ácido Fólico/genética , Deficiência de Ácido Fólico/tratamento farmacológico , Transtornos do Desenvolvimento da Linguagem/tratamento farmacológico
15.
J Neurol ; 270(7): 3329-3340, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37101094

RESUMO

Myasthenia gravis (MG) is characterized by muscle weakness caused by autoantibodies that bind to the postsynaptic membrane at the neuromuscular junction and impair acetylcholine receptor function. Weakness of respiratory muscles represents the most severe MG manifestation, and 10-15% of all patients experience an MG crisis with the need of mechanical ventilatory support at least once in their life. MG patients with respiratory muscle weakness need active immunosuppressive drug treatment long term, and they need regular specialist follow-up. Comorbidities affecting respiratory function need attention and optimal treatment. Respiratory tract infections can lead to MG exacerbations and precipitate an MG crisis. Intravenous immunoglobulin and plasma exchange are the core treatments for severe MG exacerbations. High-dose corticosteroids, complement inhibitors, and FcRn blockers represent fast-acting treatments that are effective in most MG patients. Neonatal myasthenia is a transient condition with muscle weakness in the newborn caused by mother's muscle antibodies. In rare cases, treatment of respiratory muscle weakness in the baby is required.


Assuntos
Miastenia Gravis , Doenças Neuromusculares , Doenças Respiratórias , Recém-Nascido , Humanos , Junção Neuromuscular , Debilidade Muscular/etiologia , Doenças Respiratórias/complicações
16.
Expert Rev Neurother ; 23(2): 169-177, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36786092

RESUMO

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease where muscle antibodies form against the acetylcholine receptor (AChR), MuSK, or LRP4 at the neuromuscular junction leading to weakness. Patients worry about consequences for pregnancy, giving birth, nursing, and child outcome. AREAS COVERED: This review lists the pharmacological treatments for MG in the reproductive age and gives recommendations. Consequences for pregnancy, giving birth, breastfeeding, and child outcome are discussed. EXPERT OPINION: Pyridostigmine, corticosteroids in low doses, and azathioprine are regarded as safe during pregnancy and should be continued. Mycophenolate mofetil, methotrexate, and cyclophosphamide should not be used in reproductive age. Rituximab should not be given during pregnancy. Other monoclonal IgG antibodies such as eculizumab and efgartigimod should be given only when regarded strictly necessary to avoid long-term and severe incapacity. Intravenous and subcutaneous immunoglobulin and plasma exchange are safe treatments during pregnancy and are recommended for exacerbations with moderate or severe generalized weakness. Most MG women have spontaneous vaginal deliveries. Indications for Cesarean section are obstetrical and similar to non-MG women. Neonatal myasthenia manifests as a transient weakness caused by the mother's IgG muscle antibodies and affects 10% of the babies. MG women should be supported in their wish to have children.


Assuntos
Miastenia Gravis , Doenças Neuromusculares , Criança , Recém-Nascido , Humanos , Gravidez , Feminino , Cesárea , Miastenia Gravis/terapia , Receptores Colinérgicos/uso terapêutico , Autoanticorpos , Anticorpos Monoclonais/uso terapêutico , Imunoglobulina G
17.
Front Neurol ; 13: 1025183, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36188382
18.
JAMA Neurol ; 79(11): 1130-1138, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36156660

RESUMO

Importance: Women with epilepsy are recommended high doses of folic acid before and during pregnancy owing to risk of congenital anomalies associated with antiseizure medications. Whether prenatal exposure to high-dose folic acid is associated with increases in the risk of childhood cancer is unknown. Objective: To assess whether high-dose folic acid supplementation in mothers with epilepsy is associated with childhood cancer. Design, Setting, and Participants: Observational cohort study conducted with nationwide registers in Denmark, Norway, and Sweden from 1997 to 2017. Analyses were performed during January 10, 2022, to January 31, 2022. Mother-child pairs were identified in medical birth registers and linked with information from patient, prescription, and cancer registers, as well as with sociodemographic information from statistical agencies, and were categorized by maternal diagnosis of epilepsy. The study population consisted of 3 379 171 children after exclusion of 126 711 children because of stillbirth or missing or erroneous values on important covariates. Exposures: Maternal prescription fills for high-dose folic acid tablets (≥1 mg daily) between 90 days before pregnancy start and birth. Main Outcomes and Measures: First onset of childhood cancer at younger than 20 years. Cox proportional hazards models were used to calculate adjusted hazard ratios with corresponding 95% CIs, adjusted for potential confounders. Cumulative incidence at aged 20 years was used as a measure of absolute risk. Results: The median age at the end of follow-up in the study population of 3 379 171 children was 7.3 years (IQR, 3.5-10.9 years). Among the 27 784 children (51.4% male) born to mothers with epilepsy, 5934 (21.4%) were exposed to high-dose folic acid (mean dose, 4.3 mg), with 18 exposed cancer cases compared with 29 unexposed, producing an adjusted hazard ratio of 2.7 (95% CI, 1.2-6.3), absolute risk if exposed of 1.4% (95% CI, 0.5%-3.6%), and absolute risk if unexposed of 0.6% (95% CI, 0.3%-1.1%). In children of mothers without epilepsy, 46 646 (1.4%) were exposed to high-dose folic acid (mean dose, 2.9 mg), with 69 exposed and 4927 unexposed cancer cases and an adjusted hazard ratio of 1.1 (95% CI, 0.9-1.4; absolute risk, 0.4% [95% CI, 0.3%-0.5%]). There was no association between children born to mothers with epilepsy who were prenatally exposed to antiseizure medications, but not high-dose folic acid, and an increased risk of cancer (absolute risk, 0.6%; 95% CI, 0.2%-1.3%). Conclusions and Relevance: Prenatal exposure to high-dose folic acid was associated with increased risk of cancer in children of mothers with epilepsy.


Assuntos
Epilepsia , Neoplasias , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Humanos , Masculino , Feminino , Pré-Escolar , Criança , Ácido Fólico/uso terapêutico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/etiologia , Risco , Estudos de Coortes , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Neoplasias/complicações
19.
J Neurol ; 269(11): 5901-5909, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35780399

RESUMO

BACKGROUND: Knowledge concerning exposure to abuse in adulthood and in pregnancy in people with multiple sclerosis (MS) is sparse. OBJECTIVE: To determine the occurrence of adult abuse and abuse in relation to pregnancy in women with MS and their risk of revictimization (repeated abuse as adults after childhood abuse). METHODS: This cross-sectional study comprised pregnant women from the Norwegian Mother, Father and Child Cohort study. Information on abuse was acquired through self-completed questionnaires. We used logistic regression to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: We identified 106 women with MS at enrollment through linkage with national health registries. The reference group consisted of 77,278 women without MS. Twenty-seven women (26%) with MS reported any adult abuse compared to 15,491 women (20%) without MS, aOR 1.33 (0.85-2.09). Twenty-two (21%) women with MS reported systematic emotional abuse compared to 13% without MS, aOR 1.75 (1.08-2.83). Ten women (10%) with MS reported sexual abuse, compared to 6% without MS, aOR 1.72 (0.89-3.33). More women with MS reported rape as an adult, aOR 2.37 (1.02-5.49). Women with MS had higher risk of revictimization as adults, after childhood abuse, aOR 2.23 (1.22-4.10). The risk of abuse during pregnancy or 6 months preceding pregnancy was similar between the groups. CONCLUSIONS: Women with MS had increased occurrence of systematic emotional abuse, rape, and revictimization as adults, compared to women without MS.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis , Esclerose Múltipla , Adulto , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Esclerose Múltipla/epidemiologia , Gravidez , Fatores de Risco
20.
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