Article
Clinical Neurology
Pavel Klein, Sami Aboumatar, Christian Brandt, Fang Dong, Gregory L. Krauss, Sarah Mizne, Juan Carlos Sanchez-Alvarez, Bernhard J. Steinhoff, Vicente Villanueva
Summary: This study evaluated the long-term efficacy and safety of adjunctive cenobamate in the treatment of uncontrolled focal seizures. The results showed that cenobamate reduced seizure frequency and had a high retention rate over a 48-month period. No new safety concerns were identified. These findings highlight the potential clinical benefits of cenobamate in long-term management of patients with uncontrolled focal seizures.
Article
Clinical Neurology
Jacqueline A. French, Steve S. Chung, Gregory L. Krauss, Sang Kun Lee, Maciej Maciejowski, William E. Rosenfeld, Michael R. Sperling, Marc Kamin
Summary: This study examined the long-term retention rate, safety, and tolerability of the antiseizure medication cenobamate as adjunctive treatment in adults with treatment-resistant focal seizures. Results showed sustained safety and tolerability of adjunctive cenobamate treatment up to 7.8 years, with a high probability of treatment continuation at 1-6 years. Common reasons for discontinuation included patient withdrawal, adverse events, and lack of efficacy, while the most frequent treatment-emergent adverse events reported were dizziness, headache, and somnolence.
Article
Clinical Neurology
Josemir W. Sander, William E. Rosenfeld, Jonathan J. Halford, Bernhard J. Steinhoff, Victor Biton, Manuel Toledo
Summary: Through pooling and analyzing data from multiple studies, it was found that long-term retention rates of adjunctive cenobamate therapy for individuals with uncontrolled focal seizures were consistently high, indicating cenobamate as a potentially effective and well-tolerated treatment option. The most common reasons for discontinuation of treatment were adverse events, withdrawal of consent, and other reasons.
Article
Clinical Neurology
Javier Pena-Ceballos, Patrick B. Moloney, Tudor Munteanu, Michael Doyle, Niamh Colleran, Brenda Liggan, Annette Breen, Sinead Murphy, Hany El-Naggar, Peter Widdess-Walsh, Norman Delanty
Summary: Cenobamate has been shown to significantly improve seizure control in highly active and ultra-refractory focal epilepsy patients. However, adverse events may occur at doses above 250 mg/day, limiting further improvements in seizure control.
Article
Behavioral Sciences
Ting Zhao, Hong-jian Li, Jing Yu, Ting-ting Wang, Jie Feng, Long Ma, Li Sun, Yan Sun, Lu-hai Yu
Summary: Levetiracetam has shown significant efficacy, safety, and tolerability in pediatric patients with epilepsy in Uygur, China. The seizure frequency decreased over time, with a substantial number of patients achieving seizure remission at 1, 2, and 3 years of treatment. The number of baseline ASMs and the order of levetiracetam introduction significantly impact the likelihood of seizure remission during a 3-year follow-up period.
EPILEPSY & BEHAVIOR
(2021)
Article
Clinical Neurology
Mala Manral, Rekha Dwivedi, Sheffali Gulati, Kirandeep Kaur, Ashima Nehra, Ravindra Mohan Pandey, Ashish Datt Upadhyay, Savita Sapra, Manjari Tripathi
Summary: This study investigated whether Modified Atkins diet (MAD) combined with standard drug therapy (SDT) was more effective than SDT alone in reducing seizure frequency and improving psychological outcomes in adolescents and adults with drug-resistant epilepsy (DRE). The results showed that the MAD group had significant improvements in seizure frequency and behavioral problems compared to the control group.
Article
Behavioral Sciences
Kayeong Im, Sang-Ahm Lee, Ji Hyun Kim, Dong Wook Kim, Sang Kun Lee, Dae Won Seo, Ji Woong Lee
Summary: Long-term treatment with perampanel as a first add-on therapy showed sustained improvement in seizure control, especially at low doses, without raising new safety signals. Adverse events were mainly dizziness, somnolence, anger, and irritability, but could be resolved by reducing the dose or discontinuing the medication.
EPILEPSY & BEHAVIOR
(2021)
Review
Neurosciences
Maria Antonietta Barbieri, Emilio Perucca, Edoardo Spina, Paola Rota, Valentina Franco
Summary: Cenobamate is a new antiseizure medication used for the treatment of focal seizures in adults. Its mechanisms of action include enhancing the inactivated state of sodium channels and positive modulation of GABA(A) receptors. It has high oral bioavailability and a long half-life, allowing for once-daily dosing. However, it can cause drug-drug interactions due to its effects on various liver enzymes.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2023)
Article
Clinical Neurology
Lanlan Zhang, Juan Wang, Chengzhong Wang
Summary: This study systematically investigated the efficacy and safety of adjunctive cenobamate for uncontrolled focal seizures, showing that cenobamate had favorable efficacy, especially at the dose of 400 mg, and was well tolerated.
ACTA NEUROLOGICA SCANDINAVICA
(2021)
Article
Clinical Neurology
Alvaro Beltran-Corbellini, Maria Romeral-Jimenez, Pablo Mayo, Irene Sanchez-Miranda Roman, Pablo Iruzubieta, Juan Luis Chico-Garcia, Paloma Parra-Diaz, Irene Garcia-Morales, Rafael Toledano, Angel Aledo-Serrano, Antonio Gil-Nagel
Summary: The purpose of this study was to determine the effectiveness and safety of cenobamate in patients with highly refractory focal epilepsy. The results showed that cenobamate significantly reduced seizure frequency and intensity, with a manageable safety profile.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2023)
Article
Clinical Neurology
Stephanie J. Nahas, Nada Hindiyeh, Deborah I. Friedman, Nada Elbuluk, Donald J. Kellerman, Pamela K. Foreman, Peter Schmidt
Summary: The study aimed to evaluate the safety and tolerability of M207 during long-term use for the treatment of migraine attacks. Results showed that most participants experienced cutaneous adverse reactions, with the majority of reactions being mild.
JOURNAL OF HEADACHE AND PAIN
(2021)
Article
Pharmacology & Pharmacy
Christopher T. Buckley, Olivia R. Waters, George DeMaagd
Summary: Cenobamate is an effective and generally well-tolerated adjunctive therapy for patients with drug-resistant focal epilepsy. Despite its efficacy, Drug Reaction with Eosinophilia and Systemic Symptoms remains a significant concern with cenobamate.
ANNALS OF PHARMACOTHERAPY
(2021)
Article
Clinical Neurology
Anup D. Patel, Maria Mazurkiewicz-Beldzinska, Richard F. Chin, Antonio Gil-Nagel, Boudewijn Gunning, Jonathan J. Halford, Wendy Mitchell, Michael Scott Perry, Elizabeth A. Thiele, Arie Weinstock, Eduardo Dunayevich, Daniel Checketts, Orrin Devinsky
Summary: Long-term add-on CBD treatment for LGS showed good safety and efficacy outcomes. Sustained reductions in drop and total seizure frequency were observed for up to 156 weeks, demonstrating long-term benefits of CBD treatment for patients with LGS.
Article
Clinical Neurology
Elinor Ben-Menachem, Michel Baulac, Seung Bong Hong, Jody M. Cleveland, Christoph Reichel, Anne-Liv Schulz, Gilbert Wagener, Christian Brandt
Summary: This study evaluated the long-term safety, tolerability, and efficacy of brivaracetam (BRV) in patients with epilepsy. The findings suggest that BRV is well-tolerated as a long-term adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease, with sustained improvements in focal seizure frequency.
Article
Clinical Neurology
Adam Strzelczyk, Clara Zaveta, Felix von Podewils, Gabriel Moddel, Lisa Langenbruch, Stjepana Kovac, Catrin Mann, Laurent M. Willems, Juliane Schulz, Barbara Fiedler, Gerhard Kurlemann, Susanne Schubert-Bast, Felix Rosenow, Isabelle Beuchat
Summary: The study evaluated the long-term efficacy, retention, and tolerability of add-on BRV in clinical practice. Results showed a 33% response rate at 12 months and an overall retention rate of over 50%, with good tolerability except for psychobehavioral adverse events in 10% of patients. Short-term response predictors were identified, but no significant predictors for long-term outcomes were found.
Article
Clinical Neurology
Heather Angus-Leppan, Michael R. Sperling, Vicente Villanueva
Summary: Up to 10% of people over the age of 80 experience seizures, and many do not require anti-seizure medication. The diagnosis is often made based on the patient's medical history. Targeted investigations are important for classification and risk prediction. Patients with a low risk of seizure recurrence do not usually need medication, while high-risk patients with multiple seizures and other symptoms are offered medication. Future technologies may offer better seizure monitoring and prediction, but they are not yet reliable or convenient. Therapeutic drug monitoring can be useful in confirming medication toxicity or identifying causes of breakthrough seizures. Current evidence does not support routine monitoring of medication levels. The decision to discontinue medication should be made after a discussion with the patient, considering their individual risks and preferences. Medication is usually discontinued gradually after at least two years of remission, and patients need specialist follow-up during this time.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Piero Perucca, Kate Stanley, Natasha Harris, Anne M. McIntosh, Ali A. Asadi-Pooya, Mohamad A. Mikati, Danielle M. Andrade, Patricia Dugan, Chantal Depondt, Hyunmi Choi, Erin L. Heinzen, Gianpiero L. Cavalleri, Russell J. Buono, Orrin Devinsky, Michael R. Sperling, Samuel F. Berkovic, Norman Delanty, David B. Goldstein, Terence J. O'Brien
Summary: This study investigated whether rare genetic variations influence seizure outcomes of MTLE surgery. The results showed that MTLE cases carried a higher burden of ultrarare missense variants in constrained genes and genes encoding voltage-gated cation channels. However, these genetic variations did not have a major role in the failure of MTLE surgery.
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Chris Rundfeldt, Pavel Klein, Detlev Boison, Alexander Rotenberg, Raimondo D'Ambrosio, Cliff Eastman, Benton Purnell, Madhuvika Murugan, Howard P. Goodkin, Wolfgang Loescher
Summary: This study presents a novel meglumine-based solution of topiramate (TPM) that may be well suited for clinical development. Meglumine significantly enhances the aqueous solubility of TPM and can be used to prepare drug cocktails with other antiseizure medications. Tolerability studies demonstrate excellent tolerability of the novel drug solutions.
Article
Multidisciplinary Sciences
Shennan A. Weiss, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Daniel Rubinstein, Jerome Engel Jr, Michael R. Sperling, Richard J. Staba
Summary: Fast ripples (FR) are a biomarker of epileptogenic brain. The FR resection ratio (RR) did not correlate with seizure-outcome, but the FR rate-distance radius resected difference and the FR MI mean characteristic path length RR did correlate with seizure-outcome. The diagnostic accuracy of the resection of FR events for predicting seizure freedom can be improved by using graph theoretical measures of FR networks.
SCIENTIFIC REPORTS
(2023)
Editorial Material
Clinical Neurology
Jo M. Wilmshurst, Michael R. Sperling
Editorial Material
Clinical Neurology
Pavel Klein, Gregory L. Krauss, Bernhard J. Steinhoff, Orrin Devinsky, Michael R. Sperling
Summary: Despite the approval of numerous antiseizure medications (ASMs), a significant number of epilepsy patients still experience seizures. Two new ASMs, cenobamate and fenfluramine, have shown improved efficacy in reducing seizures with sustained results. However, these medications are underutilized, likely due to limited knowledge, access restrictions, and insufficient post-launch information about their efficacy and safety. Addressing these issues can improve seizure control and ultimately reduce morbidity and mortality in epilepsy patients.
Article
Clinical Neurology
Shennan Aibel Weiss, Dawn Eliashiv, John Stern, Daniel Rubinstein, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Jerome Engel, Richard Staba, Michael R. Sperling
Summary: The mechanism by which responsive neurostimulation (RNS) reduces seizure frequency is not well understood. This study examined whether stimulation of fast ripples (FRs) generating networks differs between RNS super responders and intermediate responders. The results showed that the efficiency of the FR temporal correlational network on stimulated contacts differed significantly between the two groups. These findings suggest that RNS that targets FR networks more effectively may reduce epileptogenicity better.
Article
Neurosciences
Nora A. Herweg, Lukas Kunz, Daniel Schonhaut, Armin Brandt, Paul A. Wanda, Ashwini D. Sharan, Michael R. Sperling, Andreas Schulze-Bonhage, Michael J. Kahana
Summary: Distinct lines of research in both humans and animals have found that the hippocampus plays a specific role in spatial and episodic memory function. Concept cells in the hippocampus and surrounding areas suggest that the medial temporal lobe maps physical and semantic spaces using a similar neural architecture. This study examines the emergence of such maps using recordings from the medial temporal lobe of patients navigating a virtual environment with meaningful landmarks, and finds that the field potentials in the medial temporal lobe contain information to decode the subjects' locations and temporal sequences.
JOURNAL OF NEUROSCIENCE
(2023)
Editorial Material
Clinical Neurology
David G. Vossler
Editorial Material
Clinical Neurology
David G. Vossler
Summary: This study aimed to compare the efficacy of midazolam and propofol in treating refractory status epilepticus (RSE) and focused on management methods in resource-limited settings. The study found that patients treated with midazolam or propofol for RSE had similar baseline characteristics and outcomes. Prolonged EEG monitoring may help reduce the duration of anesthetic infusions, but this depends on the implementation of RSE management protocols.
Article
Clinical Neurology
Jonah Fox, Sarah Barnard, Shruti H. Agashe, Manisha G. Holmes, Barry Gidal, Pavel Klein, Bassel W. Abou-Khalil, Jacqueline French, Human Epilepsy Project Investigators
Summary: More than one third of patients with focal epilepsy remain on monotherapy with their initial prescribed ASM. Approximately three out of five patients transition to monotherapy with another ASM, while approximately two out of five end up on polytherapy. Patients stay on lamotrigine for a longer duration compared to levetiracetam when it is prescribed as the initial monotherapy.
Article
Clinical Neurology
David G. G. Vossler, William E. E. Rosenfeld, Sean Stern, Clarence T. T. Wade, Louis Ferrari, Wesley T. T. Kerr, Robert Wechsler
Summary: In this post hoc analysis, the sustainability of seizure reduction with cenobamate was evaluated in patients with uncontrolled focal seizures. The results demonstrated that cenobamate can lead to sustained seizure reduction, with some patients achieving complete seizure control.
Article
Clinical Neurology
Jacqueline A. French, Roger J. Porter, Emilio Perucca, Martin J. Brodie, Michael A. Rogawski, Simon Pimstone, Ernesto Aycardi, Cynthia Harden, Jenny Qian, Constanza Luzon Rosenblut, Christopher Kenney, Gregory N. Beatch
Summary: This phase 2b clinical trial showed that treatment with XEN1101 led to a significant and dose-dependent reduction in monthly seizure frequency in adults with focal-onset seizures. The results support the further development of XEN1101 for the treatment of FOSs.
Article
Clinical Neurology
Shennan A. Weiss, Itzhak Fried, Jerome Engel, Anatol Bragin, Shuang Wang, Michael R. Sperling, Robert K. S. Wong, Yuval Nir, Richard J. Staba
Summary: This study confirmed that pathological high frequency oscillations (pHFOs) occur during the UP-DOWN transition of slow wave activity and disrupt temporal correlations between brain regions. These findings suggest that pHFOs may interfere with information transmission and memory consolidation.
Article
Clinical Neurology
Levente Hadady, Michael R. Sperling, Juan Luis Alcala-Zermeno, Jacqueline A. French, Patricia Dugan, Lara Jehi, Daniel Fabo, Peter Klivenyi, Guido Rubboli, Sandor Beniczky
Summary: This study conducted external validation of previously published epilepsy surgery prediction tools using a large independent multicenter dataset and found that these tools can effectively stratify patients for surgery and freedom from disabling seizures.