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.
Peripheral neuropathy has been reported as a side effect of interferon alpha, but not with interferon beta (IFNβ) treatment. The authors assessed six patients with multiple sclerosis who developed polyneuropathy, or had exacerbation of previously subclinical neuropathy, during treatment with IFNβ. In five patients the neuropathy improved after discontinuation of treatment and in two patients it relapsed upon rechallenge.
Preoperative localization of seizure onset zones (SOZs) is an evolving field in the treatment of refractory epilepsy. Both magnetic source imaging (MSI), and the more recent EEG-correlated functional MRI (EEG-fMRI), have shown applicability in assisting surgical planning. The purpose of this study was to evaluate the capability of each method and their combination in localizing the seizure onset lobe (SL).
Krumholz et al. 1 on the management of an unprovoked first seizure and the comments that followed, especially the one by Cole and Cascino, 2 which focused on treatment guidelines.The authors reported an absolute risk reduction in seizure recurrence of 35% during the first 2 years of treatment, based on the 5 studies that randomly divided the patients to receiving or not receiving treatment after the qualifying seizure.However, it seems that being randomly assigned to one of these treatment options yielded the best chances for the patient to remain seizure-free during this period.Overall, 522 out of 1,600 (33%) patients in the randomized studies had 1-2 years seizure recurrence (tables 1 and 2 1 ), while 625 of 1,612 (39%) in the studies where physicians decided whether to recommend treatment, based on their clinical judgment, recurred (table 1 1 ; p , 0.001, x 2 ).This observation, which was not reported in the article, emphasizes the limitations of our current knowledge on the issue of treatment after a first seizure, and the complexity of factors taken into consideration while making treatment recommendations in this situation, other than the seizure prevention itself.
Our goal was to measure the absolute differential abundance of key drug transporters in human epileptogenic brain tissue and to compare them between patients and at various distances from the epileptogenic zone within the same patient. Transporter protein abundance was quantified in brain tissue homogenates from patients who underwent epilepsy surgery, using targeted proteomics, and correlations with clinical and tissue characteristics were assessed. Fourteen brain samples (including four epileptogenic hippocampal samples) were collected from nine patients. Among the quantifiable drug transporters, the abundance (median, range) ranked: breast cancer resistance protein (ABCG2/BCRP; 0.55, 0.01–3.26 pmol/g tissue) > P-glycoprotein (ABCB1/MDR1; 0.30, 0.02–1.15 pmol/g tissue) > equilibrative nucleoside transporter 1 (SLC29A1/ENT1; 0.06, 0.001–0.35 pmol/g tissue). The ABCB1/ABCG2 ratio (mean 0.27, range 0.08–0.47) was comparable with literature values from nonepileptogenic brain tissue (mean 0.5–0.8). Transporter abundance was lower in the hippocampi than in the less epileptogenic neocortex of the same patients. ABCG2/BCRP and ABCB1/MDR1 expression strongly correlated with that of glucose transporter 1 (SLC2A1/GLUT1) (r = 0.97, p < 0.001; r = 0.90, p < 0.01, respectively). Low transporter abundance was found in patients with overt vascular pathology, whereas the highest abundance was seen in a sample with normally appearing blood vessels. In conclusion, drug transporter abundance highly varies across patients and between epileptogenic and less epileptogenic brain tissue of the same patient. The strong correlation in abundance of ABCB1/MDR1, ABCG2/BCRP, and SLC2A1/GLUT1 suggests variation in the content of the functional vasculature within the tissue samples. The epileptogenic tissue can be depleted of key drug transport mechanisms, warranting consideration when selecting treatments for patients with drug-resistant epilepsy.
Abstract So-called Western treatments are based on administration of products affecting a limited number of targets that are believed to be involved in the pathogenesis of disease. Many of these products, usually administered in very high concentrations, have a significant potential for adverse effects, frequently limiting their use. In contrast, many Traditional Medical Systems make use of mixtures of botanicals. The mixtures contain several to many herbs, which in turn are comprised of hundreds of single chemical compounds in low concentrations, likely acting on multiple sites of action. An open question is whether the use of herbal medicines is more likely to be able to restore homeostasis of brain function in states of disease. Studies are now emerging of the mechanisms of action of traditionally used botanicals, providing scientific rationale in many cases for their clinical assessment in the treatments of various CNS disorders. Better understanding of the use of botanicals in CNS disorders and further testing may lead to future more effective and better tolerated treatments.
Surveys among women with epilepsy (WWE) show that they receive their essential pregnancy-related information from many sources, including the internet. Our aim was to assess the types of websites provided by searching Google for the use of four antiepileptic drugs (AEDs) during pregnancy and lactation. The search was performed on 40 computers used by health-care professionals, on 40 computers used by nonhealth-care professionals, and on 5 computers used by WWE in Israel and on 8 computers used by nonhealth-care professionals in the U.S. On each computer, a Google search was conducted for term combinations that included one AED name ("carbamazepine","valproic acid", "lamotrigine", "levetiracetam", or "Keppra") and "Pregnancy", "Lactation", or "Breastfeeding". The top three and top ten websites retrieved in every search were mapped (a total of 45 and 150 websites, respectively, from each computer). Across all searches in English, on both U.S. and Israeli computers, the majority of websites listed among the first three and first ten results were those of independent health portals. The representation of the Epilepsy Foundation website was 10% or less, and only a few results were obtained from the NIH's general public-oriented MedlinePlus. In Hebrew, results included almost exclusively Israeli or Hebrew-translated websites. As in English, results from public-oriented, professionally-written websites in Hebrew accounted for less than 50% of entries. Overall, the availability of readable and high-quality information on AEDs used by pregnant and breastfeeding women is limited. Guiding patients towards accurate web resources can help them navigate among the huge amount of available online information.
