Pharmacodynamic sodium channel blockers-induced seizure aggravation in patients with newly diagnosed focal epilepsy

Pharmacodynamic aggravation (PA) is an unpredictable increase in the frequency, the severity of existing seizures, and/or development of new seizure types despite rational (adequate for seizure type and epilepsy form) antiepileptic drug (AED) prescription. Many mechanisms and predictors of its development are still poorly understood.Objective: to analyze PA of seizures in patients with newly diagnosed focal epilepsy receiving monotherapy with sodium channel blockers with epileptiform activity index (EAI) assessment.Patients and methods. We enrolled 201 patients with newly diagnosed focal epilepsy aged 16—81 years. In twelve months, patients had five follow-up visits. At each visit, treatment tolerability and efficacy were assessed, taking into account changes in the type, severity, and frequency of seizures. Additionally, at each visit, video-electroencephalographic monitoring was performed with EAI assessment. PA of seizures occurred in patients on oxcarbazepine, carbamazepine, and lacosamide therapy.Results and discussion. Five patients with PA of seizures had increased total EAI and EAI before sleep at the second follow-up visit after sodium channel blockers prescription. Electroencephalographic correlates of PA occurred earlier than clinical manifestations. In patients with PA, the absolute increase in EAI was minimal in patients receiving oxcarbazepine, and lacosamide therapy was associated with a minimal relative increase in EAI. At the end of the follow-up, total EAI decreased by 54—80% relative to its initial value in all five patients. The difference in the total index during the first and last visits was statistically significant.Conclusion. Due to the low level of knowledge about PA of seizures, it seems necessary to consider its possibility in all cases of increased frequency, aggravation, or change in the type of seizures after the AED treatment initiation or an increase in its dose. It is also possible to use changes in total EAI and EAI before sleep as an early objective marker of PA in adults with focal epilepsy.

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Diphenytoin, riluzole and lidocaine: Three sodium channel blockers, with different mechanisms of action, decrease hippocampal epileptiform activity

Neuropharmacology ◽

10.1016/j.neuropharm.2013.04.057 ◽

2013 ◽

Vol 73 ◽

pp. 48-55 ◽

Cited By ~ 10

Author(s):

Lihong Diao ◽

Jennifer L. Hellier ◽

Jessica Uskert-Newsom ◽

Philip A. Williams ◽

Kevin J. Staley ◽

...

Keyword(s):

Sodium Channel ◽

Epileptiform Activity ◽

Mechanisms Of Action ◽

Channel Blockers ◽

Sodium Channel Blockers

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Monotherapy with valproic acid for newly diagnosed epilepsy in adults

Russian Medical Inquiry ◽

10.32364/2587-6821-2020-4-9-552-559 ◽

2020 ◽

Vol 4 (9) ◽

pp. 552-559

Author(s):

A.B. Kozhokaru ◽

◽

A.S. Orlova ◽

V.I. Shmyrev ◽

E.S. Akarachkova ◽

...

Keyword(s):

Valproic Acid ◽

Adverse Events ◽

Focal Epilepsy ◽

Activity Index ◽

Epileptiform Activity ◽

Total Duration ◽

Idiopathic Epilepsy ◽

Seizure Type ◽

Newly Diagnosed ◽

Generalized Epilepsy

Background: valproic acid (VA) is a classic, well-proven medication for the epilepsy treatment, but there have not been enough studies to evaluate its effecacy and tolerability in correlation with the epileptiform activity index (EAI) during initial monotherapy. Aim: to evaluate the efficacy and tolerability of monotherapy with VA medications in patients with newly diagnosed epilepsy. Patients and Methods: 63 patients (including 37 (58.7%) men) with focal epilepsy (FE; 24 (38.1%)) and idiopathic (genetic) generalized epilepsy (IGE; 39) over the age of 18 years (average age — 31.49±12.29 years) were included in the single-arm study (61.9%)). All patients at each visit (initially, after 1, 3, 6 and 12 months of therapy) had EEG-video monitoring with an evaluation of EAI (total; before sleep; during sleep; during fragmented awakenings; after sleep). Therapy efficacy was evaluated considering the frequency of seizures: no seizures (medically induced remission); reduced frequency by more than 50% (responders) / less than 50% (lack of effect); therapy retention; increased frequency of seizures relative to the basic level; emergence of a new seizure type (aggravation). Total duration of the study was 12 months. Results: total EAI in patients with IGE before treatment was 2.7 times higher than in patients with FE (37.41 and 13.69, respectively). 1 month after the treatment initiation, it decreased to 4.08 and 2.56 in IGE and FE, respectively (p<0.001), and continued to decrease during the entire follow-up period. Monotherapy retention was achieved in 51 (81%) patients, including 15 (62.5%) with FE and 36 (92.3%) with IGE. Intolerable adverse events developed in only 6 (9.8%) patients. Conclusion: VA is an effective medicine for the initial treatment of FE and IGE in monotherapy. KEYWORDS: idiopathic epilepsy, genetic generalized epilepsy, focal epilepsy, epileptiform activity index, valproic acid, monotherapy, adverse events. FOR CITATION: Kozhokaru A.B., Orlova A.S., Shmyrev V.I. et al. Monotherapy with valproic acid for newly diagnosed epilepsy in adults. Russian Medical Inquiry. 2020;4(9):552–559. DOI: 10.32364/2587-6821-2020-4-9-552-559.

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Efficacy assessment of levetiracetam monotherapy in newly-diagnosed epilepsy in adults using epileptiform activity index

Epilepsia and paroxyzmal conditions ◽

10.17749/2077-8333/epi.par.con.2020.024 ◽

2020 ◽

Vol 12 (2) ◽

pp. 93-104

Author(s):

V. A. Karlov ◽

A. B. Kozhokaru ◽

P. N. Vlasov ◽

A. S. Samoilov ◽

Yu. D. Udalov

Keyword(s):

Treatment Efficacy ◽

Focal Epilepsy ◽

Activity Index ◽

Epileptiform Activity ◽

Dose Titration ◽

Therapeutic Drug ◽

Newly Diagnosed ◽

Rate Decrease ◽

Seizure Rate

Abstract. Levetiracetam (LEV) is one of the most commonly prescribed antiepileptic drugs (AED). However, there were no studies on its efficacy and safety in terms of the correlation with epileptiform activity index (EAI) performed among the Russian population.Aim. To evaluate the efficacy and tolerability of LEV monotherapy in patients with newly-diagnosed epilepsy using epileptiform activity index (EAI) assessment.Materials and methods. The study included 107 patients (46 (43.0%) male and 61 (57.0%) female) with focal epilepsy (FE) (39.3%; n=42) or idiopathic generalized epilepsy (IGE) (60.7%; n=65). At each visit, video-electroencephalographic (video-EEG) monitoring was performed (baseline and in 1, 3, 6, and 12 months of the therapy). Therapeutic drug monitoring was performed at dose titration in 1 month of the therapy or in case of therapy correction. Treatment efficacy was assessed using the criteria of seizure absence (medically induced remission), seizure rate decrease by >50% (responders), seizure rate decrease by <50% – insufficient efficacy, a composite index of efficacy/tolerability (retention on treatment), and seizure rate increase compared to baseline and/or development of a new type of seizures (aggravation). Adverse events (AE) were assessed using the scale for side effects in AED treatment (SIDAED).Results. Total EAI at baseline was 5.2-fold higher in patients with IGE compared to FE patients (23.4±3.0 and 4.5±0.97, respectively). After 1 month of LEV therapy, EAI decreased to 3.4±1.1 and 1.9±0.4 in patients with IGE and FE, respectively (p<0.01). The decrease continued during the whole follow-up period. Retention on monotherapy was achieved in 82.2% (n=88/107) patients; in 87.6% (n=57/65) patients with IGE and in 73.8% (n=31/42) with FE. The rate of serious AEs during the follow-up period was 8.4% (n=9).Conclusions. LEV is an effective drug of choice for the initial treatment of newly-diagnosed FE and IGE in monotherapy along with a significant decrease in EAI. EAI is an objective measure of LEV treatment efficacy.

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