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Antiseizure medications and thyroid hormone homeostasis: Literature review and practical recommendations
Anne Maria Rochtus, Dorien Herijgers, Katrien Jansen, Brigitte Decallonne
doi : 10.1111/epi.17117
Pages: 259-270 First Published: 09 November 2021
Thyroid hormones play an essential role in central nervous system development, normal physiological brain function, and repair mechanisms. On one hand, thyroid hormone alterations influence cortical excitability, and on the other hand antiseizure medications (ASMs) are associated with alterations in thyroid hormone metabolism. Although this interaction has long been described, and epilepsy is a common and chronic neurological disease, studies describing the interplay are often small and retrospective. We performed a systematic review of the current literature on epilepsy, ASMs, and thyroid hormone metabolism according to PRISMA guidelines. Forty-seven studies were included. Most studies were retrospective cross-sectional studies (n = 25) and investigated thyroid function alterations in patients on older ASMs such as phenobarbital, phenytoin, carbamazepine, and valproate. Overall, almost one third of patients with epilepsy had thyroid hormone alterations, especially patients on valproate (25%) and carbamazepine (10%–25%). Studies with patients receiving polytherapy are scarce, but reported a higher risk for hypothyroidism in patients with older age (p = .004), female sex (p = .014), longer duration of epilepsy (p = .001), intractable epilepsy (p = .009), and polytherapy. Studies on newer ASMs are also limited, and further studies on an interplay with thyroid hormone homeostasis are essential to improve the care for epilepsy patients. ASMs are associated with alterations in thyroid hormone metabolism. Thyroid function monitoring is indicated in patients on ASMs, especially those with refractory epilepsy and those on polytherapy. We provide a practical guidance for thyroid function monitoring for the clinician taking care of patients on ASMs.
Not your usual drug-drug interactions: Monoclonal antibody–based therapeutics may interact with antiseizure medications
Erez Berman, Iris Noyman, Mordekhay Medvedovsky, Dana Ekstein, Sara Eyal
doi : 10.1111/epi.17147
Pages: 271-289 First Published: 29 December 2021
Therapeutic monoclonal antibodies (mAbs) have emerged as the fastest growing drug class. As such, mAbs are increasingly being co-prescribed with other drugs, including antiseizure medications (ASMs). Although mAbs do not share direct targets or mechanisms of disposition with small-molecule drugs (SMDs), combining therapeutics of both types can increase the risk of adverse effects and treatment failure. The primary goal of this literature review was identifying mAb-ASM combinations requiring the attention of professionals who are treating patients with epilepsy. Systematic PubMed and Embase searches (1980–2021) were performed for terms relating to mAbs, ASMs, drug interactions, and their combinations. Additional information was obtained from documents from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Evidence was critically appraised - key issues calling for clinicians’ consideration and important knowledge gaps were identified, and practice recommendations were developed by a group of pharmacists and epileptologists. The majority of interactions were attributed to the indirect effects of cytokine-modulating antibodies on drug metabolism. Conversely, strong inhibitors or inducers of drug-metabolizing enzymes or drug transporters could potentially interact with the cytotoxic payload of antibody-drug conjugates, and ASMs could alter mAb biodistribution. In addition, mAbs could potentiate adverse ASM effects. Unfortunately, few studies involved ASMs, requiring the formulation of class-based recommendations. Based on the current literature, most mAb-ASM interactions do not warrant special precautions. However, specific combinations should preferably be avoided, whereas others require monitoring and potentially adjustment of the ASM doses. Reduced drug efficacy or adverse effects could manifest days to weeks after mAb treatment onset or discontinuation, complicating the implication of drug interactions in potentially deleterious outcomes. Prescribers who treat patients with epilepsy should be familiar with mAb pharmacology to better anticipate potential mAb-ASM interactions and avoid toxicity, loss of seizure control, or impaired efficacy of mAb treatment.
Minimum standards for inpatient long-term video-electroencephalographic monitoring: A clinical practice guideline of the International League Against Epilepsy and International Federation of Clinical Neurophysiology
William O. Tatum, Jayanti Mani, Kazutaka Jin, Jonathan J. Halford, David Gloss, Firas Fahoum, Louis Maillard, Ian Mothersill, Sandor Beniczky
doi : 10.1111/epi.16977
Pages: 290-315 First Published: 13 December 2021
ILAE clinical practice recommendations for the medical treatment of depression in adults with epilepsy
Marco Mula, Martin J Brodie, Bertrand de Toffol, Alla Guekht, Hrvoje Hecimovic, Kousuke Kanemoto, Andres M Kanner, Antonio L Teixeira, Sarah J Wilson
doi : 10.1111/epi.17140
Pages: 316-334 First Published: 05 December 2021
The aim of this document is to provide evidence-based recommendations for the medical treatment of depression in adults with epilepsy. The working group consisted of members of an ad hoc Task Force of the International League Against Epilepsy (ILAE) Commission on Psychiatry, ILAE Executive and the International Bureau for Epilepsy (IBE) representatives. The development of these recommendations is based on a systematic review of studies on the treatment of depression in adults with epilepsy, and a formal adaptation process of existing guidelines and recommendations of treatment of depression outside epilepsy using the ADAPTE process. The systematic review identified 11 studies on drug treatments (788 participants, class of evidence III and IV); 13 studies on psychological treatments (998 participants, class of evidence II, III and IV); and 2 studies comparing sertraline with cognitive behavioral therapy (CBT; 155 participants, class of evidence I and IV). The ADAPTE process identified the World Federation of Societies of Biological Psychiatry guidelines for the biological treatment of unipolar depression as the starting point for the adaptation process. This document focuses on first-line drug treatment, inadequate response to first-line antidepressant treatment, and duration of such treatment and augmentation strategies within the broader context of electroconvulsive therapy, psychological, and other treatments. For mild depressive episodes, psychological interventions are first-line treatments, and where medication is used, selective serotonin reuptake inhibitors (SSRIs) are first-choice medications (Level B). SSRIs remain the first-choice medications (Level B) for moderate to severe depressive episodes; however, in patients who are partially or non-responding to first-line treatment, switching to venlafaxine appears legitimate (Level C). Antidepressant treatment should be maintained for at least 6Â months following remission from a first depressive episode but it should be prolonged to 9Â months in patients with a history of previous episodes and should continue even longer in severe depression or in cases of residual symptomatology until such symptoms have subsided.
Survey on the worldwide availability and affordability of antiseizure medications: Report of the ILAE Task Force on Access to Treatment
Virginia Pironi, Ornella Ciccone, Ettore Beghi, Hazel Paragua-Zuellig, Archana A. Patel, Giorgia Giussani, Elisa Bianchi, Viviana Venegas, Federico Vigevano, the ILAE Task Force on Access to Treatment
doi : 10.1111/epi.17155
Pages: 335-351 First Published: 03 January 2022
Influences on the trajectory and subsequent outcomes in CDKL5 deficiency disorder
Helen Leonard, Mohammed Junaid, Kingsley Wong, Alex A. Aimetti, Elia Pestana Knight, Jenny Downs
doi : 10.1111/epi.17125
Pages: 352-363 First Published: 27 November 2021
The study investigated the effect of seizure and medication burden at initial contact with the International CDKL5 Disorder Database on subsequent development and clinical severity and compared quality of life among those whose development progressed, remained stable, or regressed between baseline and follow-up.
Increased expression of complement components in tuberous sclerosis complex and focal cortical dysplasia type 2B brain lesions
Victoria-Elisabeth Gruber, Mark J. Luinenburg, Katrin Colleselli, Verena Endmayr, Jasper J. Anink, Till S. Zimmer, Floor Jansen, Peter Gosselaar, Roland Coras, Theresa Scholl, Ingmar Blumcke, José Pimentel, Johannes A. Hainfellner, Romana Höftberger, Karl Rössler, Martha Feucht, Jackelien van Scheppingen, Eleonora Aronica, Angelika Mühlebner
doi : 10.1111/epi.17139
Pages: 364-374 First Published: 14 December 2021
Increasing evidence supports the contribution of inflammatory mechanisms to the neurological manifestations of epileptogenic developmental pathologies linked to mammalian target of rapamycin (mTOR) pathway dysregulation (mTORopathies), such as tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD). In this study, we aimed to investigate the expression pattern and cellular distribution of the complement factors C1q and C3 in resected cortical tissue of clinically well-characterized patients with TSC and FCD2B.
Genetic testing for the epilepsies: A systematic review
Beth R. Sheidley, Jennifer Malinowski, Amanda L. Bergner, Louise Bier, David S. Gloss, Weiyi Mu, Maureen M. Mulhern, Emily J. Partack, Annapurna Poduri
doi : 10.1111/epi.17141
Pages: 375-387 First Published: 10 December 2021
Numerous genetic testing options for individuals with epilepsy have emerged over the past decade without clear guidelines regarding optimal testing strategies. We performed a systematic evidence review (SER) and conducted meta-analyses of the diagnostic yield of genetic tests commonly utilized for patients with epilepsy. We also assessed nonyield outcomes (NYOs) such as changes in treatment and/or management, prognostic information, recurrence risk determination, and genetic counseling.
Mutations associated with epileptic encephalopathy modify EAAT2 anion channel function
Peter Kovermann, Yulia Kolobkova, Arne Franzen, Christoph Fahlke
doi : 10.1111/epi.17154
Pages: 388-401 First Published: 28 December 2021
Mutations in the gene solute carrier family member 1A2 (SLC1A2) encoding the excitatory amino acid transporter 2 (EAAT2) are associated with severe forms of epileptic encephalopathy. EAAT2 is expressed in glial cells and presynaptic nerve terminals and represents the main l-glutamate uptake carrier in the mammalian brain. It does not only function as a secondary active glutamate transporter, but also as an anion channel. How naturally occurring mutations affect these two transport functions of EAAT2 and how such alterations cause epilepsy is insufficiently understood.
“Do I still have epilepsy?� Epilepsy identity 15–20 years after anterior temporal lobectomy
Honor Coleman, Anne McIntosh, Sarah J. Wilson
doi : 10.1111/epi.17143
Pages: 402-413 First Published: 04 December 2021
Identity is a multifaceted construct, comprising personal identity (sense of being a unique individual) and social identity (the sense-of-self derived from membership of social groups). Social identity involves explicit identification with a group (“I am …�) and implicit behaviors or attitudes associated with group membership. Following successful treatment with surgery, patients with epilepsy can undergo a complex and lasting change in personal identity. To date, there has been no research into postoperative social epilepsy identity (SEI). We sought to examine SEI 15–20 years post-surgery, and the relationship between SEI and satisfaction with surgery, psychosocial improvements, mood, and health-related quality of life (HRQoL).
Norwegian population-based study of long-term effects, safety, and predictors of response of vagus nerve stimulation treatment in drug-resistant epilepsy: The NORPulse study
Konstantin H. Kostov, Hrisimir Kostov, PÃ¥l Gunnar Larsson, Oliver Henning, Christian Alexander Cornelius Eckmann, Morten Ingvar Lossius, Jukka Peltola
doi : 10.1111/epi.17152
Pages: 414-425 First Published: 21 December 2021
This study was undertaken to evaluate the efficacy of vagus nerve stimulation (VNS) over time, and to determine which patient groups derive the most benefit.
Long-term cannabidiol treatment for seizures in patients with tuberous sclerosis complex: An open-label extension trial
Elizabeth A. Thiele, E. Martina Bebin, Francis Filloux, Patrick Kwan, Rachael Loftus, Farhad Sahebkar, Steven Sparagana, James Wheless
doi : 10.1111/epi.17150
Pages: 426-439 First Published: 27 December 2021
To evaluate the long-term safety and efficacy of add-on cannabidiol (CBD) in patients with seizures associated with tuberous sclerosis complex (TSC) in the open-label extension (OLE) of the randomized, placebo-controlled phase 3 trial GWPCARE6 (NCT02544763). Results of an interim (February 2019 data cut) analysis are reported.
Association between antiseizure medications and quality of life in epilepsy: A mediation analysis
Meng Wang, Kevin Perera, Colin B. Josephson, Mubasiru Lamidi, Oluwaseyi A. Lawal, Oluwagbohunmi Awosoga, Pamela Roach, Scott B. Patten, Samuel Wiebe, Tolulope T. Sajobi
doi : 10.1111/epi.17153
Pages: 440-450 First Published: 20 December 2021
The relationship between antiseizure medications (ASMs), which improve health outcomes by controlling seizures, and health-related quality of life (HRQOL) is poorly understood and may involve intermediate variables. We evaluated the potential mediators of the association between ASMs and HRQOL.
Relative importance of clinical outcomes and safety risks of antiseizure medication monotherapy for patients and physicians: Discrete choice experiment eliciting preferences in real-world study "VOTE"
Felix Rosenow, Yaroslav Winter, Iryna Leunikava, Marcus Brunnert, Lars Joeres, Jessie Sutphin, Marco Boeri, Jasmine Smith, Flavio Villani, Christian Brandt
doi : 10.1111/epi.17137
Pages: 451-462 First Published: 17 December 2021
This study was undertaken to elicit patients' preferences for attributes characterizing antiseizure medication (ASM) monotherapy options before treatment consultation, and to explore the trade-offs patients consider between treatment efficacy and risks of side effects. Further objectives were to explore how treatment consultation may affect patient preferences, to elicit physicians' preferences in selecting treatment, and to compare patient and physician preferences for treatment.
Abnormal functional connectivity profiles predict drug responsiveness in patients with temporal lobe epilepsy
Kangrun Wang, Fangfang Xie, Chaorong Liu, Langzi Tan, Jialinzi He, Ping Hu, Min Zhang, Ge Wang, Fenghua Chen, Bo Xiao, Weihua Liao, Lili Long
doi : 10.1111/epi.17142
Pages: 463-473 First Published: 07 December 2021
This work was undertaken to study the functional connectivity differences between non-seizure-free and seizure-free patients with temporal lobe epilepsy (TLE) and to identify imaging predictors for drug responsiveness in TLE.
Accelerated long-term forgetting in adult patients with genetic generalized epilepsy
Kristijonas Puteikis, Peter Wolf, Rūta Mameniškienė
doi : 10.1111/epi.17144
Pages: 474-482 First Published: 10 December 2021
Accelerated long-term forgetting (ALF) has been demonstrated among children but not adults with genetic generalized epilepsy (GGE). We investigated (1) how forgetting patterns of verbal and visuospatial material differ between patients with GGE and healthy controls (HCs) and (2) whether ALF is associated with ictal or interictal epileptic activity.
Correcting for physiological ripples improves epileptic focus identification and outcome prediction
Willemiek J. E. M. Zweiphenning, Nicolás von Ellenrieder, François Dubeau, Laurence Martineau, Lorella Minotti, Jeffery A. Hall, Stephan Chabardes, Roy Dudley, Philippe Kahane, Jean Gotman, Birgit Frauscher
doi : 10.1111/epi.17145
Pages: 483-496 First Published: 16 December 2021
The integration of high-frequency oscillations (HFOs; ripples [80–250 Hz], fast ripples [250–500 Hz]) in epilepsy evaluation is hampered by physiological HFOs, which cannot be reliably differentiated from pathological HFOs. We evaluated whether defining abnormal HFO rates by statistical comparison to region-specific physiological HFO rates observed in the healthy brain improves identification of the epileptic focus and surgical outcome prediction.
Early alterations of the neuronal network processing whisker-related sensory signal during absence epileptogenesis
Emel Laghouati, Florian Studer, Antoine Depaulis, Isabelle Guillemain
doi : 10.1111/epi.17151
Pages: 497-509 First Published: 16 December 2021
Epileptogenesis is the particular process during which the epileptic network builds up progressively before the onset of the first seizures. Whether physiological functions are impacted by this development of epilepsy remains unclear. To explore this question, we used Genetic Absence Epilepsy Rats From Strasbourg (GAERS), in which spike-and-wave discharges are initiated in the whisker primary somatosensory cortex (wS1) and first occur during cortical maturation. We studied the development of both the epileptic and the physiological wS1 circuits during cortical maturation to understand the interactions between them and the consequences for the animals' behavior.
Epilepsia – February 2022 – Announcements
doi : 10.1111/epi.17170
Pages: 510-511 First Published: 01 February 2022
