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1.
Ann Neurol ; 93(3): 551-562, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36433783

RESUMO

OBJECTIVE: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype. METHODS: We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose. The outcome was nongenetic MCM and specific subtypes. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) with log-binomial regression and propensity score weights. RESULTS: There was a higher crude risk of any MCM in pregnancies exposed to lamotrigine monotherapy (n = 8,339) compared to ASM-unexposed pregnancies (n = 4,866,362), but not after confounder adjustment (aRR = 0.97, 95% CI = 0.87-1.08). Compared to lamotrigine, there was an increased risk of malformations associated with valproate (n = 2,031, aRR = 2.05, 95% CI = 1.70-2.46) and topiramate (n = 509, aRR = 1.81, 95% CI = 1.26-2.60), which increased in a dose-dependent manner. We found no differences in malformation risk for carbamazepine (n = 2,674, aRR = 0.91, 95% CI = 0.72-1.15), oxcarbazepine (n = 1,313, aRR = 1.09, 95% CI = 0.83-1.44), or levetiracetam (n = 1,040, aRR = 0.78, 95% CI = 0.53-1.13). Valproate was associated with several malformation subtypes, including nervous system, cardiac, oral clefts, clubfoot, and hypospadias, whereas lamotrigine and carbamazepine were not. INTERPRETATION: Topiramate is associated with an increased risk of MCM similar to that associated with valproate, but lower doses may mitigate the risks for both drugs. Conversely, we found no increased risks for lamotrigine, carbamazepine, oxcarbazepine, or levetiracetam, which is reassuring. ANN NEUROL 2023;93:551-562.


Assuntos
Anormalidades Induzidas por Medicamentos , Epilepsia , Gravidez , Masculino , Feminino , Humanos , Ácido Valproico/efeitos adversos , Lamotrigina/uso terapêutico , Topiramato/uso terapêutico , Epilepsia/tratamento farmacológico , Oxcarbazepina/uso terapêutico , Levetiracetam/uso terapêutico , Estudos de Coortes , Anticonvulsivantes/uso terapêutico , Carbamazepina , Benzodiazepinas/uso terapêutico
2.
Epilepsia ; 65(8): 2397-2411, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38804650

RESUMO

OBJECTIVE: Research points to disparities in disease burden and access to medical care in epilepsy. We studied the association between socioeconomic status (SES) and antiseizure medication (ASM) use in pregnancies with maternal epilepsy. METHODS: We conducted a cross-sectional study consisting of 21 130 pregnancies with maternal epilepsy identified from Nordic registers during 2006-2017. SES indicators included cohabitation status, migrant background, educational attainment, and household income. Main outcomes were the proportion and patterns of ASM use from 90 days before pregnancy to birth. We applied multiple imputation to handle SES variables with 2%-4% missingness. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using modified Poisson regression with the highest SES category as reference. RESULTS: Mothers with the highest education and the highest income quintile used ASMs least frequently (56% and 53%, respectively). We observed increased risks of ASM discontinuation prior to or during the first trimester for low SES. The risk estimates varied depending on the SES indicator from aRR = 1.27 for low income (95% CI: 1.03-1.57) to aRR = 1.66 for low education (95% CI: 1.30-2.13). Migrant background was associated with ASM initiation after the first trimester (aRR 2.17; 95% CI 1.88-2.52). Low education was associated with the use of valproate during pregnancy in monotherapy (aRR 1.70; 95% CI 1.29-2.24) and in polytherapy (aRR 2.65; 95% CI 1.66-4.21). Low education was also associated with a 37% to 39% increased risk of switching from one ASM to another depending on the ASM used. For the other SES indicators, aRRs of switching varied from 1.16 (foreign origin; 95% CI 1.08-1.26) to 1.26 (not married or cohabiting; 95% CI 1.17-1.36). SIGNIFICANCE: Low SES was associated with riskier patterns of ASM use: discontinuation, late initiation, and switching during pregnancy. These findings may reflect unplanned pregnancies, disparities in access to preconception counseling, and suboptimal care.


Assuntos
Anticonvulsivantes , Epilepsia , Complicações na Gravidez , Humanos , Feminino , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Gravidez , Anticonvulsivantes/uso terapêutico , Adulto , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Estudos Transversais , Fatores Socioeconômicos , Países Escandinavos e Nórdicos/epidemiologia , Adulto Jovem , Classe Social , Sistema de Registros
3.
Epilepsia ; 65(6): 1698-1708, 2024 Jun.
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.


Assuntos
Anticonvulsivantes , Epilepsia , Ácido Fólico , Padrões de Prática Médica , Complicações na Gravidez , Humanos , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/uso terapêutico , Epilepsia/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/administração & dosagem , Gravidez , Adulto , Noruega/epidemiologia , Dinamarca/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , Complicações na Gravidez/tratamento farmacológico , Suécia/epidemiologia , Estudos Retrospectivos , Adulto Jovem , Suplementos Nutricionais
4.
Cephalalgia ; 44(4): 3331024241248846, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38663979

RESUMO

BACKGROUND: Migraine is common in women of reproductive age. Migraine's episodic manifestation and acute and preventive pharmacological treatment options challenge studying drug safety for this condition during pregnancy. To improve such studies, we aimed to develop algorithms to identify and characterize migraines in electronic healthcare registries and to assess the level of care. METHODS: We linked four registries to detect pregnancies from 2009-2018 and used three algorithms for migraine identification: i) diagnostic codes, ii) triptans dispensed, and iii) a combination of both. We assessed migraine severity using dispensed drugs as proxies. ICD-10 diagnostic subcodes of migraine (G43) allowed the allocation of four subtypes: complicated and/or status migrainosus; with aura; without aura; other/unspecified. RESULTS: We included 535,089 pregnancies in 367,908 women with available one-year lookback. The prevalence of migraines identified was 2.9%-4.3% before, and 0.8%-1.5% during pregnancy, depending on algorithm used. Pregnant women with migraine were mostly managed in primary care. CONCLUSIONS: Primary care data in combination with drug dispensation records were instrumental for identification of migraine in electronic healthcare registries. Data from secondary care and drug dispensations allow better characterization of migraines. Jointly, these algorithms may contribute to improved perinatal pharmacoepidemiological studies in this population by addressing confounding by maternal migraine indication.


Assuntos
Transtornos de Enxaqueca , Complicações na Gravidez , Sistema de Registros , Humanos , Feminino , Gravidez , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Noruega/epidemiologia , Adulto , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/diagnóstico , Estudos de Coortes , Triptaminas/uso terapêutico , Algoritmos , Adulto Jovem
5.
Cephalalgia ; 44(5): 3331024241251488, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38690640

RESUMO

BACKGROUND: We aimed to develop the first machine learning models to predict citation counts and the translational impact, defined as inclusion in guidelines or policy documents, of headache research, and assess which factors are most predictive. METHODS: Bibliometric data and the titles, abstracts, and keywords from 8600 publications in three headache-oriented journals from their inception to 31 December 2017 were used. A series of machine learning models were implemented to predict three classes of 5-year citation count intervals (0-5, 6-14 and, >14 citations); and the translational impact of a publication. Models were evaluated out-of-sample with area under the receiver operating characteristics curve (AUC). RESULTS: The top performing gradient boosting model predicted correct citation count class with an out-of-sample AUC of 0.81. Bibliometric data such as page count, number of references, first and last author citation counts and h-index were among the most important predictors. Prediction of translational impact worked optimally when including both bibliometric data and information from the title, abstract and keywords, reaching an out-of-sample AUC of 0.71 for the top performing random forest model. CONCLUSION: Citation counts are best predicted by bibliometric data, while models incorporating both bibliometric data and publication content identifies the translational impact of headache research.


Assuntos
Bibliometria , Pesquisa Biomédica , Cefaleia , Aprendizado de Máquina , Ciência Translacional Biomédica , Pesquisa Biomédica/estatística & dados numéricos , Ciência Translacional Biomédica/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Publicações Periódicas como Assunto , Curva ROC , Área Sob a Curva , Autoria , Algoritmo Florestas Aleatórias , Humanos , Conjuntos de Dados como Assunto
6.
Cephalalgia ; 44(8): 3331024241268212, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39149980

RESUMO

OBJECTIVE: The objective of this study was to describe and discuss patterns of migraine medication use in the entire Norwegian population. METHODS: In this nationwide, observational study, all individuals with a migraine-related prescription between 2010 and 2020 were identified using the Norwegian Prescription Database. The outcomes of interest were the incidence and 1-year prevalence of migraine medication users, as well as individuals with triptan overuse. Patterns of medication use were statistically compared between women and men adjusted for age, year of treatment start, comorbidities and county of residence calculating adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: We identified 327,904 migraine medication users. The incidence ranged from 0.39% to 0.46%, and the 1-year prevalence increased from 1.99% to 2.99%. Preventive use increased >50% during the study period. Preventives were significantly more often prescribed to women than to men (39.72% vs. 33.75%; aOR 1.41, 95% CI 1.38 to 1.44). Triptan overuse was significantly more common among women, but women with overuse were more often using preventives, as compared to men (56.64% vs 52.69%; aOR = 1.43, 95% CI 1.37 to 1.49). CONCLUSION: The prevalence of medically treated migraine is low. Overuse of triptans is frequent, especially among women. Clinicians should be encouraged to try out different triptans, recognize triptan overuse, and prescribe preventives when indicated.


Assuntos
Transtornos de Enxaqueca , Sistema de Registros , Triptaminas , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/epidemiologia , Noruega/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Triptaminas/uso terapêutico , Adolescente , Prevalência , Analgésicos/uso terapêutico
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.
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
9.
Cephalalgia ; 43(3): 3331024221148398, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36786371

RESUMO

BACKGROUND: Migraine has a largely unexplained connection with sleep and is possibly related to a dysfunction of thalamocortical systems and cortical inhibition. In this study we investigate the effect of insufficient sleep on cortical sensorimotor processing in migraine. METHODS: We recorded electroencephalography during a sensorimotor task from 46 interictal migraineurs and 28 controls after two nights of eight-hour habitual sleep and after two nights of four-hour restricted sleep. We compared changes in beta oscillations of the sensorimotor cortex after the two sleep conditions between migraineurs, controls and subgroups differentiating migraine subjects usually having attacks starting during sleep and not during sleep. We included preictal and postictal recordings in a secondary analysis of temporal changes in relation to attacks. RESULTS: Interictally, we discovered lower beta synchronisation after sleep restriction in sleep related migraine compared to non-sleep related migraine (p=0.006) and controls (p=0.01). No differences were seen between controls and the total migraine group in the interictal phase. After migraine attacks, we observed lower beta synchronisation (p<0.001) and higher beta desynchronisation (p=0.002) after sleep restriction closer to the end of the attack compared to later after the attack. CONCLUSION: The subgroup with sleep related migraine had lower sensorimotor beta synchronisation after sleep restriction, possibly related to dysfunctional GABAergic inhibitory systems. Sufficient sleep during or immediately after migraine attacks may be of importance for maintaining normal cortical excitability.


Assuntos
Transtornos de Enxaqueca , Córtex Sensório-Motor , Humanos , Estudos Cross-Over , Privação do Sono/complicações , Eletroencefalografia
10.
Cephalalgia ; 43(1): 3331024221128273, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36620891

RESUMO

BACKGROUND: Oxygen inhalation aborts cluster headache attacks, and case reports show the effect of continuous positive airway pressure. The aim of this study was to investigate the prophylactic effect of continuous positive airway pressure in chronic cluster headache. METHODS: This was a randomized placebo-controlled triple-blind crossover study using active and sham continuous positive airway pressure treatment for chronic cluster headache. Patients entered a one month's baseline period before randomly being assigned to two months' active continuous positive airway pressure treatment followed by a four weeks' washout period and two months' sham continuous positive airway pressure or vice versa. Primary outcome measure was number of cluster headache attacks/week. RESULTS: Of the 30 included participants (12 males, median age 49.5 years, min-max 20-66 years), 25 completed both treatment/sham cycles (two discontinued, three lost to follow-up). The median number of cluster headache attacks per week was reduced from 8.25 (0.75-89.75) attacks to 6.25 (0-56.00) attacks for active continuous positive airway pressure and to 7.50 (0.50-43.75) attacks for sham continuous positive airway pressure, but there was no difference in active versus sham (p = 0.904). One patient had a serious adverse event during active treatment, none occurred during sham treatment. CONCLUSIONS: Continuous positive airway pressure treatment did not reduce the number of cluster headache attacks compared to sham treatment in chronic cluster headache patients. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03397563.


Assuntos
Cefaleia Histamínica , Humanos , Masculino , Pessoa de Meia-Idade , Cefaleia Histamínica/terapia , Pressão Positiva Contínua nas Vias Aéreas , Estudos Cross-Over , Método Duplo-Cego , Resultado do Tratamento
11.
J Neurol Neurosurg Psychiatry ; 93(6): 645-650, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35379699

RESUMO

OBJECTIVE: To study whether exposure to childhood emotional, sexual or physical abuse is associated with subsequent multiple sclerosis (MS) development. METHODS: A nationwide, prospective cohort study based on participants in the Norwegian Mother, Father and Child cohort study. Enrolment took place 1999-2008, with follow-up until 31 December 2018. Childhood abuse before age 18 years was obtained from self-completed questionnaires. We identified MS diagnoses through data-linkage with national health registries and hospital records. The Cox model was used to estimate HRs for MS with 95% CIs, adjusting for confounders and mediators. RESULTS: In this prospective cohort study, 14 477 women were exposed to childhood abuse and 63 520 were unexposed. 300 women developed MS during the follow-up period. 71 of these (24%) reported a history of childhood abuse, compared with 14 406 of 77 697 (19%) women that did not develop MS. Sexual abuse (HR 1.65, 95% CI 1.13 to 2.39) and emotional abuse (HR 1.40, 95% CI 1.03 to 1.90) in childhood were both associated with an increased risk of developing MS. The HR of MS after exposure to physical abuse was 1.31 (95% CI 0.83 to 2.06). The risk of MS was further increased if exposed to two (HR 1.66, 95% CI 1.04 to 2.67) or all three abuse categories (HR 1.93, 95% CI 1.02 to 3.67). INTERPRETATION: Childhood sexual and emotional abuse were associated with an increased risk of developing MS. The risk was higher when exposed to several abuse categories, indicating a dose-response relationship. Further studies are needed to identify underlying mechanisms.


Assuntos
Experiências Adversas da Infância , Maus-Tratos Infantis , Esclerose Múltipla , Adolescente , Criança , Maus-Tratos Infantis/psicologia , Estudos de Coortes , Feminino , Humanos , Masculino , Esclerose Múltipla/epidemiologia , Estudos Prospectivos , Fatores de Risco
12.
Epilepsia ; 63(7): 1822-1834, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35352343

RESUMO

OBJECTIVE: This study was undertaken to examine the prevalence of self-reported experiences with abuse in pregnant women with epilepsy and the association between having experienced abuse and childbirth expectations, particularly the fear of childbirth. METHODS: We performed a cross-sectional study of women with and without epilepsy enrolled in the Norwegian Mother, Father, and Child Cohort Study 1999-2008. Data on epilepsy diagnosis; antiseizure medication (ASM) use; emotional, physical, and sexual abuse; and childbirth expectations were collected from questionnaires completed during gestational Weeks 17-19 and 30. RESULTS: Our study population included 295 women with ASM-treated epilepsy, 318 women with ASM-untreated epilepsy, and 93 949 women without epilepsy. A total of 115 women (47%) with ASM-treated and 132 women (57%) with ASM-untreated epilepsy reported any emotional, physical, or sexual abuse, compared to 25 100 women (32%) without epilepsy. The adjusted odds ratios (aORs) for having experienced any abuse were 1.8 (95% confidence interval [CI] = 1.4-2.3) and 1.8 (95% CI = 1.4-2.2) for ASM-treated and ASM-untreated epilepsy, respectively. A total of 29 women (11%) with ASM-treated and 34 women (11%) with ASM-untreated epilepsy reported having been raped, compared to 3088 women (4%) without epilepsy (aORs = 2.8 [95% CI = 1.8-4.1] and 2.9 [95% CI = 2.0-4.2], respectively). In nulliparous women with ASM-untreated epilepsy, having experienced abuse was associated with fear of childbirth; 22 women (31%) with abuse experiences reported fear of childbirth compared to five women (7%) with no experience of abuse (aOR = 5.4 [95% CI = 1.7-17.2]). This association was not seen in multiparous women or in women with ASM-treated epilepsy. SIGNIFICANCE: More women with epilepsy reported emotional, physical, and sexual abuse than women without epilepsy. Such experiences may be associated with childbirth expectations.


Assuntos
Epilepsia , Delitos Sexuais , Criança , Estudos de Coortes , Estudos Transversais , Epilepsia/epidemiologia , Pai , Medo , Feminino , Humanos , Masculino , Mães/psicologia , Noruega/epidemiologia , Parto/psicologia , Gravidez , Gestantes/psicologia , Prevalência , Autorrelato , Delitos Sexuais/psicologia , Inquéritos e Questionários
13.
Epilepsia ; 62(12): 2968-2980, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34590314

RESUMO

OBJECTIVE: Antiseizure medication (ASM) use interacts with vitamin B status in nonpregnant epilepsy populations. We aimed to examine the association between ASM and vitamin B status in pregnant women with epilepsy. METHODS: We performed a cross-sectional study of pregnancies in women with epilepsy enrolled in the Norwegian Mother, Father and Child Cohort Study from 1999 to 2008. Data on ASM and vitamin supplement use were collected from questionnaires. We analyzed maternal plasma concentrations of ASM and metabolites of folate, including unmetabolized folic acid (UMFA), riboflavin (vitamin B2), pyridoxine (vitamin B6), and niacin (vitamin B3) during gestational weeks 17-19. RESULTS: We included 227 singleton pregnancies exposed to ASM with available plasma samples (median maternal age 29 years, range 18 to 41 years). From the preconception period to gestational week 20, any supplement of folic acid was reported in 208 of pregnancies (94%), riboflavin in 72 (33%), pyridoxine in 77 (35%), and niacin in 45 (20%). High ASM concentrations correlated with high concentrations of UMFA and inactive folate metabolites, and with low concentrations of riboflavin and metabolically active pyridoxine. There was no association between ASM and niacin status. SIGNIFICANCE: ASM concentrations during pregnancy were associated with vitamin B status in pregnant women with epilepsy. Additional studies are needed to determine the clinical impact of these findings, and to define the optimal vitamin doses that should be recommended to improve pregnancy outcomes.


Assuntos
Epilepsia , Niacina , Complexo Vitamínico B , Adolescente , Adulto , Criança , Estudos de Coortes , Estudos Transversais , Epilepsia/tratamento farmacológico , Feminino , Ácido Fólico/uso terapêutico , Humanos , Niacina/uso terapêutico , Gravidez , Gestantes , Piridoxina/uso terapêutico , Riboflavina/uso terapêutico , Complexo Vitamínico B/metabolismo , Complexo Vitamínico B/uso terapêutico , Adulto Jovem
14.
Epilepsia ; 62(12): 2981-2993, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34585373

RESUMO

OBJECTIVE: Prenatal exposure to the antiseizure medication (ASM) valproate is associated with an increased risk of congenital malformations, but warnings against the use of valproate in pregnancy were not issued until 2009. The objective was to study how early administrative health registers could have identified the teratogenic risk associated with valproate. METHODS: This was a population-based cohort study of individual-linked data from Danish health care and socioeconomic registers including children born in Denmark between January 1, 1997 and December 31, 2014. Information on ASM use, including valproate, in pregnancy was obtained from the Danish National Prescription Registry. Children identified with major congenital malformations from the Danish National Patient Register and the Danish Register of Causes of Death were included. Using logistic regression models, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for major congenital malformations during the first year of life in children with and without prenatal exposure to ASMs adjusted for potential confounders. RESULTS: Among the 895 507 children (males, 51.3%), 31 790 (3.6%) were diagnosed with a major congenital malformation in the first year of life. In the analyses including children born in 1997, the risk of major congenital malformations among children prenatally exposed to valproate compared with children not exposed to ASMs was increased by a fully adjusted OR (aOR) of 3.95 (95% CI = 1.65-9.47). With the addition of data from the following years, the teratogenic effect of valproate was further substantiated, as the precision of the estimate improved (1997-2014: aOR = 2.44, 95% CI = 1.80-3.30). SIGNIFICANCE: Using Danish health care data, we were able to identify a teratogenic risk associated with prenatal valproate exposure in children born in 1997, which is much earlier than prospective clinical cohorts. Health registry data represent an important tool for early identification of risk associated with drugs in pregnancy.


Assuntos
Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Anticonvulsivantes/efeitos adversos , Criança , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Gravidez , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , Sistema de Registros , Ácido Valproico/efeitos adversos
15.
Eur J Neurol ; 28(7): 2443-2455, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33852763

RESUMO

Many clinicians lack experience in managing trigeminal autonomic cephalalgias (TACs) in pregnancy and lactation. In addition to cluster headache, TACs include hemicrania continua, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing/autonomic symptoms (SUNCT/SUNA). Treating these rare, severe headache conditions often requires off-label drugs that have uncertain teratogenic potential. In the last few years, several new treatment options and safety documentation have emerged, but clinical guidelines are lacking. This narrative review aimed to provide an updated clinical guide and good clinical practice recommendations for the management of these debilitating headache disorders in pregnancy and lactation.


Assuntos
Cefaleia Histamínica , Síndrome SUNCT , Cefalalgias Autonômicas do Trigêmeo , Aleitamento Materno , Cefaleia Histamínica/diagnóstico , Cefaleia Histamínica/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Humanos , Gravidez , Cefalalgias Autonômicas do Trigêmeo/diagnóstico , Cefalalgias Autonômicas do Trigêmeo/tratamento farmacológico
16.
J Headache Pain ; 20(1): 77, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288756

RESUMO

BACKGROUND: The migraine brain seems to undergo cyclic fluctuations of sensory processing. For instance, during the preictal phase, migraineurs experience symptoms and signs of altered pain perception as well as other well-known premonitory CNS-symptoms. In the present study we measured EEG-activation to non-painful motor and sensorimotor tasks in the different phases of the migraine cycle by longitudinal measurements of beta event related desynchronization (beta-ERD). METHODS: We recorded electroencephalography (EEG) of 41 migraine patients and 31 healthy controls. Each subject underwent three EEG recordings on three different days with classification of each EEG recording according to the actual migraine phase. During each recording, subjects performed one motor and one sensorimotor task with the flexion-extension movement of the right wrist. RESULTS: Migraine patients had significantly increased beta-ERD and higher baseline beta power at the contralateral C3 electrode overlying the primary sensorimotor cortex in the preictal phase compared to the interictal phase. We found no significant differences in beta-ERD or baseline beta power between interictal migraineurs and controls. CONCLUSION: Increased preictal baseline beta activity may reflect a decrease in pre-activation in the sensorimotor cortex. Altered pre-activation may lead to changes in thresholds for inhibitory responses and increased beta-ERD response, possibly reflecting a generally increased preictal cortical responsivity in migraine. Cyclic fluctuations in the activity of second- and third-order afferent somatosensory neurons, and their associated cortical and/or thalamic interneurons, may accordingly also be a central part of the migraine pathophysiology.


Assuntos
Transtornos de Enxaqueca/fisiopatologia , Córtex Sensório-Motor/fisiopatologia , Adulto , Mapeamento Encefálico , Eletroencefalografia , Feminino , Humanos , Estudos Longitudinais , Masculino , Percepção da Dor
18.
Cephalalgia ; 38(4): 718-729, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28478712

RESUMO

Background The migraine brain is believed to have altered cortical excitability compared to controls and between migraine cycle phases. Our aim was to evaluate post-activation excitability through post-movement beta event related synchronization (PMBS) in sensorimotor cortices with and without sensory discrimination. Subjects and methods We recorded EEG of 41 migraine patients and 31 healthy controls on three different days with classification of days in relation to migraine phases. During each recording, subjects performed one motor and one sensorimotor task with the right wrist. Controls and migraine patients in the interictal phase were compared with repeated measures (R-) ANOVA and two sample Student's t-test. Migraine phases were compared to the interictal phase with R-ANOVA and paired Student's t-test. Results The difference between PMBS at the contralateral and ipsilateral sensorimotor cortex was altered throughout the migraine cycle. Compared to the interictal phase, we found decreased PMBS at the ipsilateral sensorimotor cortex in the ictal phase and increased PMBS in the preictal phase. Lower ictal PMBS was found in bilateral sensorimotor cortices in patients with right side headache predominance. Conclusion The cyclic changes of PMBS in migraine patients may indicate that a dysfunction in deactivation and interhemispheric inhibition of the sensorimotor cortex is involved in the migraine attack cascade.


Assuntos
Ritmo beta/fisiologia , Sincronização de Fases em Eletroencefalografia/fisiologia , Transtornos de Enxaqueca/fisiopatologia , Movimento/fisiologia , Córtex Sensório-Motor/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
20.
Epilepsy Behav ; 62: 251-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27513352

RESUMO

OBJECTIVE: The aim of this study was to investigate life satisfaction in women with epilepsy during and after pregnancy. METHODS: The study was based on the Norwegian Mother and Child Cohort Study, including 102,265 women with and without epilepsy from the general population. Investigation took place at pregnancy weeks 15-19 and 6 and 18months postpartum. Women with epilepsy were compared with a reference group without epilepsy. RESULTS: The proportion of women with epilepsy was 0.6-0.7% at all three time points. Women with epilepsy reported lower life satisfaction and self-esteem both during and after pregnancy compared with the references. Single parenting correlated negatively with life satisfaction in epilepsy during the whole study period. Epilepsy was associated with lower levels of relationship satisfaction and higher levels of work strain during pregnancy and lower levels of self-efficacy and satisfactory somatic health 18months postpartum. Adverse life events, such as divorce, were more common in women with epilepsy compared with the references, and fewer women with epilepsy had a paid job 18months postpartum. SIGNIFICANCE: Reduced life satisfaction associated with epilepsy during and after pregnancy showed that, even in a highly developed welfare society, women with epilepsy struggle. Mothers with epilepsy and their partners should be examined for emotional complaints and partnership satisfaction during and after pregnancy. Validated screening tools are available for such measures.


Assuntos
Epilepsia/psicologia , Mães/psicologia , Satisfação Pessoal , Período Pós-Parto/psicologia , Autoimagem , Adulto , Estudos de Coortes , Feminino , Humanos , Noruega , Poder Familiar , Gravidez , Autoeficácia , Adulto Jovem
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