Epilepsy currents
Networks Inhibited and Networks Excited: Loss of Consciousness in Epilepsy
2023-04-12
Epilepsy Currents, Ahead of Print.
Distinct Signatures of Loss of Consciousness in Focal Impaired Awareness Versus Tonic-Clonic Seizures Juan E, Górska U, Kozma C, Papantonatos C, Bugnon T, Denis C, Kremen V, Worrell G, Struck AF, Bateman LM, Merricks EM, Blumenfeld H, Tononi G, Schevon C, Boly M. Brain. 20235;146(1):109-123. doi:10.1093/brain/awac291Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of loss of consciousness and intracranial EEG activity during 129 focal impaired awareness and 50 focal to bilateral tonic-clonic from 41 patients. We characterized intracranial EEG changes both in the seizure onset zone and in areas remote from the seizure onset zone with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of intracranial EEG sleep-like activities: slow-wave activity (1-4 Hz) and beta/delta ratio (a validated marker of cortical activation) during focal impaired awareness versus focal to bilateral tonic-clonic. Second, we quantified differences between focal to bilateral tonic-clonic and focal impaired awareness for a marker validated to detect ictal cross-frequency coupling: phase-locked high gamma (high-gamma phased-locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index. Third, we assessed changes in intracranial EEG activity preceding and accompanying behavioural generalization onset and their correlation with electromyogram channels. In addition, we analysed human cortical multi-unit activity recorded with Utah arrays during three focal to bilateral tonic-clonic seizures. Compared to focal impaired awareness, focal to bilateral tonic-clonic seizures were characterized by deeper loss of consciousness, even before generalization occurred. Unlike during focal impaired awareness, early loss of consciousness before generalization was accompanied by paradoxical decreases in slow-wave activity and by increases in high-gamma activity in parieto-occipital and temporal cortex. After generalization, when all patients displayed loss of consciousness, stronger increases in slow-wave activity were observed in parieto-occipital cortex, while more widespread increases in cortical activation (beta/delta ratio), ictal cross-frequency coupling (phase-locked high gamma) and ictal recruitment (epileptogenicity index). Behavioural generalization coincided with a whole-brain increase in high-gamma activity, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of focal to bilateral tonic-clonic revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the seizure onset zone. Overall, these results indicate that unlike during focal impaired awareness, the neural signatures of loss of consciousness during focal to bilateral tonic-clonic consist of paradoxical increases in cortical activation and neuronal firing found most consistently in posterior brain regions. These findings suggest differences in the mechanisms of ictal loss of consciousness between focal impaired awareness and focal to bilateral tonic-clonic and may account for the more negative prognostic consequences of focal to bilateral tonic-clonic.
Fonte: Epilepsy currents, Dario J. Englot
Registry-Based Phenotyping to Improve the Diagnosis of Autoimmune Encephalitis
2023-04-12
Epilepsy Currents, Ahead of Print.
Seizure Semiology in Antibody-Associated Autoimmune Encephalitis Kaaden T, Madlener M, Angstwurm K, Bien CG, Bogarin Y, Doppler K, Finke A, Gerner ST, Reimann G, Häusler M, Handreka R, Hellwig K, Kaufmann M, Kellinghaus C, Koertvelyessy P, Kraft A, Lewerenz J, Menge T, Paliantonis A, von Podewils F, Prüss H, Rauer S, Ringelstein M, Rostásy K, Schirotzek I, Schwabe J, Sokolowski P, Suesse M, Sühs K-W, Surges R, Tauber SC, Thaler F, Bergh FT, Urbanek C, Wandinger K-P, Wildemann B, Mues S, Zettl U, Leypoldt F, Melzer N, Geis C, Malter M, Kunze A; The Generate Study Group. Neurol Neuroimmunol Neuroinflamm. 2022;9(6):e200034. doi:10.1212/NXI.0000000000200034Background and Objectives:To assess seizure characteristics in antibody (ab)-associated autoimmune encephalitis (ab +AE) with the 3 most prevalent abs against N-methyl-D-aspartate receptor (NMDAR), leucine rich glioma-inactivated protein 1 (LGI1), and glutamic acid decarboxylase (GAD).Methods:Multicenter nationwide prospective cohort study of the German Network for Research in Autoimmune Encephalitis.Results:Three hundred twenty patients with ab + AE were eligible for analysis: 190 NMDAR+, 89 LGI1+, and 41 GAD+. Seizures were present in 113 (60%) NMDAR+, 69 (78%) LGI1+, and 26 (65%) GAD+ patients and as leading symptoms for diagnosis in 53 (28%) NMDAR+, 47 (53%) LGI+, and 20 (49%) GAD+ patients. Bilateral tonic-clonic seizures occurred with almost equal frequency in NMDAR+ (38/51, 75%) and GAD+ (14/20, 70%) patients, while being less common in LGI1+ patients (27/59, 46%). Focal seizures occurred less frequently in NMDAR+(67/113; 59%) than in LGI1+ (54/69, 78%) or in GAD+ patients (23/26; 88%). An aura with deja-vu phenomenon was nearly specific in GAD+ patients (16/20, 80%). Faciobrachial dystonic seizures (FBDS) were uniquely observed in LGI1+ patients (17/59, 29%). Status epilepticus was reported in one-third of NMDAR+ patients, but only rarely in the 2 other groups. The occurrence of seizures was associated with higher disease severity only in NMDAR+ patients.Discussion:Seizures are a frequent and diagnostically relevant symptom of ab + AE. Whereas NMDAR+ patients had few localizing semiological features, semiology in LGI1+ and GAD+ patients pointed toward a predominant temporal seizure onset. FBDS are pathognomonic for LGI1 + AE. Status epilepticus seems to be more frequent in NMDAR + AE. Epileptic Phenotypes in Autoimmune Encephalitis: From Acute Symptomatic Seizures to Autoimmune-Associated Epilepsy Matricardi S, Casciato S, Bozzetti S, Mariotto S, Stabile A, Freri E, Deleo F, Sartori S, Nosadini M, Pappalardo I, Meletti S, Giovannini G, Zucchi E, Di Bonaventura C, Di Gennaro G, Ferrari S, Zuliani L, Zoccarato M, Vogrig A, Lattanzi S, Michelucci R, Gambardella A, Ferlazzo E, Fusco L, Granata T, Villani F; On behalf of the Immune Epilepsies Study Group of the Italian League Against Epilepsy. J Neurol Neurosurg Psychiatry. 2022;93(11). doi:10.1136/jnnp-2022-329195Objective:To describe the clinical and paraclinical findings, treatment options and long-term outcomes in autoimmune encephalitis (AE), with a close look to epilepsy.Methods:In this retrospective observational cohort study, we enrolled patients with new-onset seizures in the context of AE. We compared clinical and paraclinical findings in patients with and without evidence of antibodies.Results:Overall, 263 patients (138 females; median age 55 years, range 4–86) were followed up for a median time of 30 months (range 12–120). Antineuronal antibodies were detected in 63.50%. Antibody-positive patients had multiple seizure types (p = 0.01) and prevalent involvement of temporal regions (p = 0.02). A higher prevalence of episodes of SE was found in the antibody-negative group (p < 0.001). Immunotherapy was prescribed in 88.60%, and effective in 61.80%. Independent predictors of favourable outcome of the AE were early immunotherapy (p < 0.001) and the detection of antineuronal surface antibodies (p = 0.01). Autoimmune-associated epilepsy was the long-term sequela in 43.73%, associated with cognitive and psychiatric disturbances in 81.73%. Independent predictors of developing epilepsy were difficult to treat seizures at onset (p = 0.04), a high number of antiseizure medications (p < 0.001), persisting interictal epileptiform discharges at follow-up (p < 0.001) and poor response to immunotherapy during the acute phase (p < 0.001).Conclusions:The recognition of seizures secondary to AE represents a rare chance for aetiology-driven seizures management. Early recognition and treatment at the pathogenic level may reduce the risk of long-term irreversible sequelae. However, the severity of seizures at onset is the major risk factor for the development of chronic epilepsy. This study provides class IV evidence for management recommendations.
Fonte: Epilepsy currents, Claude Steriade
Exploring CITEs of Inflammation in the Human Epilepsy Brain
2023-04-11
Epilepsy Currents, Ahead of Print.
Single-Cell Transcriptomics and Surface Epitope Detection in Human Brain Epileptic Lesions Identifies Pro-Inflammatory Signaling Kumar P, Lim A, Hazirah SN, Chua CJH, Ngoh A, Poh SL, Yeo TH, Lim J, Ling S, Sutamam NB, Petretto E, Low DCY, Zeng L, Tan EK, Arkachaisri T, Yeo JG, Ginhoux F, Chan D, Albani S. Nat Neurosci. 2022;25(7):956-966. doi:10.1038/s41593-022-01095-5Epileptogenic triggers are multifactorial and not well understood. Here we aimed to address the hypothesis that inappropriate pro-inflammatory mechanisms contribute to the pathogenesis of refractory epilepsy (non-responsiveness to antiepileptic drugs) in human patients. We used single-cell cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to reveal the immunotranscriptome of surgically resected epileptic lesion tissues. Our approach uncovered a pro-inflammatory microenvironment, including extensive activation of microglia and infiltration of other pro-inflammatory immune cells. These findings were supported by ligand-receptor (LR) interactome analysis, which demonstrated potential mechanisms of infiltration and evidence of direct physical interactions between microglia and T cells. Together, these data provide insight into the immune microenvironment in epileptic tissue, which may aid the development of new therapeutics.
Fonte: Epilepsy currents, Tore Eid
Magnetic Resonance Imaging in Status Epilepticus: Useful Scrying Board or Expensive Stopwatch?
2023-03-30
Epilepsy Currents, Ahead of Print.
Association of Peri-Ictal MRI Abnormalities With Mortality, Antiseizure Medications Refractoriness, and Morbidity in Status Epilepticus Bonduelle T, Ollivier M, Trin K, Thomas B, Daubigney A, Michel V, De Montaudouin M, Marchal C, Aupy J. Neurology. 2022. doi:10.1212/WNL.0000000000201599. Online ahead of print.Background and objectives:Status epilepticus (SE) is a life-threatening emergency requiring a prompt assessment of patient prognosis to guide management. Magnetic resonance imaging (MRI) allows the identification of peri-ictal MRI abnormalities (PMA) and provides insight into brain structural modifications induced by SE. However, little is known about the significance of PMA in SE prognosis. The aim of this study was to determine whether PMA are associated with an increased mortality in SE, and to establish the association between PMA and refractoriness to antiseizure medications, complications encountered and induced morbidity.Methods:We conducted a retrospective observational cohort study including all eligible consecutive patients over 15 years-old and hospitalized with SE at Bordeaux University Hospital (France), between January 2015 and December 2019. The primary endpoint was in-hospital mortality. Together with a dedicated neuroradiological reassessment, baseline characteristics, in-hospital death, SE characterization, drug refractoriness and following outcome in survivors were assessed by comprehensive medical review.Results:Of 307 patients included, 79 (26%) showed PMA related to SE. Demographic, functional status at baseline and median delay between SE onset and MRI exam were similar in PMA-positive and PMA-negative group. In-hospital death occurred in 15% (45/307) patients and was significantly higher in the PMA-positive group (27%, 21/79 vs 11%, 24/228; p<0.001). In multivariate analysis, the presence of PMA (odds ratio [OR] 2.86, 95% confidence interval [CI] 1.02-8.18; p=0.045), together with SE duration ([OR] 1.01, 95% CI 1.01-1.02; p=0.007), older age at SE onset ([OR] 1.05, 95% CI 1.01-1.09; p=0.013), preexisting ultimately fatal comorbidity ([OR] 4.01, 95% CI 1.56-10.6; p=0.004) and acute lesional SE etiology ([OR] 3.74, 95% CI 1.45-10.2; p=0.007) were independent predictors associated with in-hospital death. Patients with PMA had a higher risk of refractory SE (71 vs 33%, p<0.001). Among survivors, delayed onset epilepsy (40% vs 21%, p=0.009) occurred more frequently in the PMA-positive group.Discussion:PMA-positive cases had a higher mortality rate in the largest cohort so far to assess the prognosis value of PMA in SE. As a non-invasive and easily available tool, PMA represents a promising structural biomarker for developing a personalized approach to prognostication in SE patients receiving MRI. Association of Ictal Imaging Changes in Status Epilepticus and Neurological Deterioration Cornwall CD, Dahl SM, Nguyen N, Roberg LE, Monsson O, Krøigård T, Beier CP. Epilepsia. 2022;63(11):2970-2980. doi:10.1111/epi.17404Objective:In patients with status epilepticus (SE), the clinical significance of ictal changes on magnetic resonance imaging (MRI) is insufficiently understood. We here studied whether the presence of ictal MRI changes was associated with neurological deterioration at discharge.Methods:The retrospective cohort comprised all identifiable patients treated at Odense University Hospital in the period 2008-2017. All amenable MRIs were systemically screened for ictal changes. Patient demographics, electroencephalography, seizure characteristics, treatment, and SE duration were assessed. Neurological status was estimated before and after SE. The predefined endpoint was the association of neurological deterioration and ictal MRI changes.Results:Of 261 eligible patients, 101 received at least one MRI during SE or within 7 days after cessation; 43.6% (44/101) had SE due to non- or less brain-damaging etiologies. Patients who received MRI had a longer duration of SE, less frequently had a history of epilepsy, and were more likely to have SE due to unknown causes. Basic characteristics (including electroencephalographic features defined by the Salzburg criteria) did not differ between patients with (n = 20) and without (n = 81) ictal MRI changes. Timing of MRI was important; postictal changes were rare within the first 24 h and hardly seen >5 days after cessation of SE. Ictal MRI changes were associated with a higher risk of neurological deterioration at discharge irrespective of etiology. Furthermore, they were associated with a longer duration of SE and higher long-term mortality that reached statistical significance in patients with non- or less brain-damaging etiologies.Significance:In this retrospective cohort, ictal changes on MRI were associated with a higher risk of neurological deterioration at discharge and, possibly, with a longer duration of SE and poorer survival.
Fonte: Epilepsy currents, Nicolas Gaspard
Anti-Epileptogenesis: Some Roads Lead to Losartan
2023-03-30
Epilepsy Currents, Ahead of Print.
Association Between Angiotensin Receptor Blocker Therapy and Incidence of Epilepsy in Patients With Hypertension Doege C, Luedde M, Kostev K. JAMA Neurol. 2022;79(12):1296-1302. doi:10.1001/JAMANEUROL.2022.3413Importance: Arterial hypertension is associated with an increased incidence of epilepsy. Results from animal studies suggest that angiotensin receptor blocker (ARB) therapy could inhibit epileptic seizures. However, there is a lack of clinical data to support the use of ARB therapy in humans. Objective: To assess whether ARB therapy is associated with a decreased incidence of epilepsy in patients with hypertension. Design, setting, and participants: This cohort study obtained data from the Disease Analyzer database (IQVIA) on patients aged 18 years or older who had hypertension and at least 1 antihypertensive drug prescription. Patients were treated at 1274 general practices between January 2010 and December 2020 in Germany. Data were available for 1 553 875 patients who had been prescribed at least 1 antihypertensive drug. Patients diagnosed with epilepsy before or up to 3 months after the index date were excluded. A total of 168 612 patients were included in propensity score matching. Patients treated with 1 of 4 antihypertensive drug classes (β-blockers, ARBs, angiotensin-converting enzyme inhibitors, and calcium channel blockers [CCBs]) were matched to each other using propensity scores. Main outcomes and measures: The main outcome of the study was the incidence of epilepsy associated with ARB therapy compared with other antihypertensive drug classes. Cox regression models were used to study the association between the incidence of epilepsy and ARBs compared with all other antihypertensive drug classes as a group. Results: The study included a total of 168 612 patients, with 42 153 in each antihypertensive drug class. The mean [SD] age of patients was 62.3 [13.5] years, and 21 667 (51.4%) were women. The incidence of epilepsy within 5 years was lowest among patients treated with ARBs (0.27% at 1 year, 0.63% at 3 years, 0.99% at 5 years) and highest among patients receiving β-blockers and CCBs (0.38% for both β-blockers and CCBs at 1 year; 0.91% for β-blockers and 0.93% for CCBs at 3 years; β-blockers, 1.47%; and CCBs, 1.48% at 5 years). Angiotensin receptor blocker therapy was associated with a significantly decreased incidence of epilepsy (hazard ratio, 0.77; 95% CI, 0.65-0.90) compared with the other drug classes as a group. Conclusions and relevance: In this cohort study of patients with hypertension, ARB therapy was associated with a significantly decreased incidence of epilepsy. The findings suggest antihypertensive drugs could be used as a novel approach for preventing epilepsy in patients with arterial hypertension.
Fonte: Epilepsy currents, Rani A. Sarkis
The BEST Conceivable Way to Talk About Epilepsy Biomarkers
2023-03-30
Epilepsy Currents, Ahead of Print.
The search for valid biomarkers to aid in epilepsy diagnosis and management is a major goal of the Epilepsy Research Benchmarks. Many papers and grants answer this call by searching for new biomarkers from a wide range of disciplines. However, the academic use of the word “biomarker” is often imprecise. Without proper definition, such work is not well-prepared to progress to the next step of translating these biomarkers into clinical use. In 2016, the Food and Drug Administration and National Institutes of Health collaborated to develop the BEST (Biomarkers, EndpointS, and other Tools) Resource as a guide to adopt formal definitions that aid in pushing successful biomarkers toward regulatory approval. Using the vignette of high-frequency oscillations, which have been proposed as a potential biomarker of several potential aspects of epilepsy, we demonstrate how improper use of the term “biomarker,” and lack of a clear context of use, can lead to confusion and difficulty obtaining regulatory approval. Similar conditions are likely in many areas of biomarker research. This Resource should be adopted by all researchers developing epilepsy biomarkers. Adopting the BEST guidelines will improve reproducibility, guide research objectives toward translation, and better target the Epilepsy Benchmarks.
Fonte: Epilepsy currents, Stephen V. Gliske
Brand Name Versus Generic?
2023-03-30
Epilepsy Currents, Ahead of Print.
Changes in the Use of Brand Name and Generic Medications and Total Prescription Cost Among Medicare Beneficiaries With Epilepsy Terman SW, Lin CC, Kerr WT, DeLott LB, Callaghan BC, Burke JF. Neurology. 2022;99(8):e751-e761. doi:10.1212/WNL.0000000000200779 Background and Objective:To characterize trends in antiseizure medication (ASM) fills and total prescription costs in people with epilepsy.Methods:This was a retrospective cohort study of beneficiaries with epilepsy (ASM, plus ICD codes) in a 20% random Medicare sample, with continuous Fee-For-Service coverage (Parts A, B, and D) in 2008–2018. We summed the number of pill days and costs (adjusted to 2018 dollars) per person-year for each ASM. ASMs were categorized into brand versus generic, first versus newer generation, and enzyme inducers versus noninducers.Results:There were 77,000–133,000 beneficiaries with epilepsy per year. The most common ASM was phenytoin in 2008, which shifted to levetiracetam in 2018 (2008: phenytoin 25%, levetiracetam 14%; 2018: phenytoin 9%, levetiracetam 27%). Brand name (2008: 56%; 2018: 14%), first-generation (2008: 55%; 2018: 32%), and enzyme-inducing ASMs (2008: 44%; 2018: 24%) each decreased over time as a proportion of pill days. The number of brand pill days per person-year initially decreased (e.g., 2008: 250; 2009: 121; 2010: 96) but then plateaued (2013–2018: between 66 and 69) given a notable increase in lacosamide pill days per person (2008: 0; 2018: 20). Total brand name costs per year initially decreased 2008–2010 (2008: $150 million; 2010: $72 million) but then increased after 2010 (2018: $256 million). In 2018, brand name ASMs represented 79% of costs despite representing only 14% of pill days, a 1-year pill supply became 277% more expensive for brand name medications but 42% less expensive for generic medications over time (2008: brand ∼$2,800 versus generic ∼$800; 2018: brand ∼$10,700 versus generic ∼$460), and many common brand name ASMs cost approximately 10-fold more per pill day than their generic equivalents.Discussion:First-generation and enzyme-inducing ASMs waned from 2008 to 2018. Although brand name ASMs initially waned translating into lower costs and potentially higher value care, after 2010, brand name costs markedly increased because of increasing use of lacosamide plus a 277% increase in per-pill cost of brand name ASMs. Brand name ASMs represented a minority of prescriptions, but the majority of costs.
Fonte: Epilepsy currents, Gewalin Aungaroon
Ripples of Hyperexcitability in Epilepsy, Autism, and Inattention
2023-01-23
Epilepsy Currents, Volume 23, Issue 2, Page 97-98, March–April 2023.
The Association Between Early Childhood Onset Epilepsy and Attention-Deficit Hyperactivity Disorder (ADHD) in 3237 Children and Adolescents With Autism Spectrum Disorder (ASD): A Historical Longitudinal Cohort Data Linkage Study Carson L, Parlatini V, Safa T, Baig B, Shetty H, Phillips-Owen J, Prasad V, Downs J. Eur Child Adolesc Psychiatry. 2022. doi:10.1007/s00787-022-02041-3 Children and young people with Autism Spectrum Disorder (ASD) have an increased risk of comorbidities, such as epilepsy and Attention-Deficit/Hyperactivity Disorder (ADHD). However, little is known about the relationship between early childhood epilepsy (below age 7) and later ADHD diagnosis (at age 7 or above) in ASD. In this historical cohort study, we examined this relationship using an innovative data source, which included linked data from routinely collected acute hospital paediatric records and childhood community and inpatient psychiatric records. In a large sample of children and young people with ASD (N = 3237), we conducted a longitudinal analysis to examine early childhood epilepsy as a risk factor for ADHD diagnosis while adjusting for potential confounders, including socio-demographic characteristics, intellectual disability, family history of epilepsy and associated physical conditions. We found that ASD children and young people diagnosed with early childhood epilepsy had nearly a twofold increase in risk of developing ADHD later in life, an association which persisted after adjusting for potential confounders (adjusted OR = 1.72, CI95% = 1.13-2.62). This study suggests that sensitive monitoring of ADHD symptoms in children with ASD who have a history of childhood epilepsy may be important to promote early detection and treatment. It also highlights how linked electronic health records can be used to examine potential risk factors over time for multimorbidity in neurodevelopmental conditions.
Fonte: Epilepsy currents, Jay A. Salpekar
Too Much of a Good Thing? High-Dose Folic Acid in Pregnancy and Childhood Cancer
2023-01-23
Epilepsy Currents, Volume 23, Issue 2, Page 102-104, March–April 2023.
Cancer Risk in Children of Mothers With Epilepsy and High-Dose Folic Acid Use During Pregnancy Vegrim HM, Dreier JW, Alvestad S, Gilhus NE, Gissler M, Igland J, Leinonen MK, Tomson T, Sun Y, Zoega H, Christensen J, Bjørk MH. JAMA Neurol. 2022;79(11):1-10. doi:10.1001/jamaneurol.2022.2977. Epub ahead of print. PMID: 36156660.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.
Fonte: Epilepsy currents, Elizabeth E. Gerard
Optimizing Care for Pregnancy in Epilepsy: The Need to Address Anxiety and Depression Symptoms
2023-01-23
Epilepsy Currents, Volume 23, Issue 2, Page 99-101, March–April 2023.
Prospective Cohort Study of Depression During Pregnancy and the Postpartum Period in Women With Epilepsy vs Control Groups Meador KJ, Stowe ZN, Brown CA, Robalino CP, Matthews AG, Kalayjian LA, Voinescu PE, Gerard EE, Penovich P, Gedzelman E, Cavitt J, Pennell PB. MONEAD Investigator Group. Neurology. 2022;99(15): e1573-e1583. doi:10.1212/WNL.0000000000200958 Background and Objective:Assess the incidence and factors associated with major depressive episodes (MDE) and symptoms of depression and anxiety during pregnancy and postpartum periods in pregnant women with epilepsy (PWWE) compared to healthy pregnant women (HPW) and to non-pregnant women with epilepsy (NPWWE) in comparable timeframes. Previous studies have reported higher rates of postpartum depression in women with epilepsy compared to women without epilepsy. However, the incidence of MDE using a structured interview during pregnancy and postpartum has not been directly compared to control groups, and the comparison of depression and anxiety symptoms and the role of associated factors remain ambiguous.Methods:The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a multicenter NIH-funded prospective observational parallel-group cohort study of PWWE and their children. This report examines mood disorders. Unlike prior epilepsy pregnancy studies, the Structured Clinical Interview for DSM-IV (SCID) provided lifetime diagnoses, and repeated SCID mood modules assessed for MDE, the a priori primary outcome. Symptoms of depression (Beck Depression Inventory [BDI], Edinburg Postnatal Depression Scale [EPDS]) and anxiety (Beck Anxiety Inventory [BAI]) were also assessed along with multiple clinical factors.Results:The study included PWWE (n = 331) and HPW (n = 102) during pregnancy and postpartum, and NPWWE (n = 102) at comparable times. No difference in SCID-diagnosed MDE incidence was found across groups, but BDI depressive symptoms were worse during pregnancy in PWWE vs NPWWE, and during postpartum vs HPW and NPWWE. BAI anxiety symptoms were worse during pregnancy in PWWE vs HPW and NPWWE, and during postpartum vs HPW. Factors associated with MDE during pregnancy/postpartum for PWWE included >1 seizure/90 days, anticonvulsant polytherapy, unplanned pregnancy, and lifetime history of mood disorder. Suicidal ideation from BDI or EPDS was related to BAI anxiety symptoms.Discussion:Although SCID-based MDE did not differ across groups, this prospective study confirms higher rates of psychiatric symptoms in patients with epilepsy during pregnancy and postpartum, provides new data on associated factors, and underscores the importance of anxiety in risk for depression and thoughts of death/dying or suicide. Given the risks, PWWE should be routinely assessed, and symptomatic patients should be offered treatment.Trial registration information:The study is registered at ClinicalTrials.gov as NCT01730170.
Fonte: Epilepsy currents, Heidi M. Munger Clary