The ups and downs of alkyl‐carbamates in epilepsy therapy: How does cenobamate differ?

Abstract

Since 1955, several alkyl‐carbamates have been developed for the treatment of anxiety and epilepsy, including meprobamate, flupirtine, felbamate, retigabine, carisbamate, and cenobamate. They have each enjoyed varying levels of success as antiseizure drugs; however, they have all been plagued by the emergence of serious and sometimes life‐threatening adverse events. In this review, we compare and contrast their predominant molecular mechanisms of action, their antiseizure profile, and where possible, their clinical efficacy. The preclinical, clinical, and mechanistic profile of the prototypical ...

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Brief potentially ictal rhythmic discharges and paroxysmal fast activity as scalp electroencephalographic biomarkers of seizure activity and seizure onset zone

Abstract

Objective

The electroencephalographic (EEG) terms “brief potentially ictal rhythmic discharges” (BIRDs) and “paroxysmal fast activity” (PFA) are considered distinct entities; however, their definitions overlap, and they may have similar clinical significance. We investigated their clinical significance and their association with seizures and the seizure onset zone (SOZ).

Methods

We retrospectively identified an adult cohort (July 2015 to March 2018) whose long‐term (>12 h) EEGs in any setting reported BIRDs (>4 Hz, lasting .5–10 s) and/or PFA. Different frequency cutoffs for PFA (>13 Hz or ≥8 Hz) were tested ...

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Symptomatology of carbamazepine‐ and oxcarbazepine‐induced hyponatremia in people with epilepsy

Abstract

Objective

To ascertain whether adverse effects experienced by people taking carbamazepine or oxcarbazepine could be attributed to carbamazepine‐ or oxcarbazepine‐induced hyponatremia (COIH).

Methods

We performed an observational study, collecting data between 2017 and 2019 on serum sodium levels and adverse effects retrospectively in people with epilepsy while receiving treatment with either carbamazepine (CBZ) or oxcarbazepine (OXC). We defined hyponatremia as sodium level ≤134 mEq/L and severe hyponatremia as sodium level ≤128 mEq/L. Adverse effects experienced were compared between groups of individuals with and without hyponatremia.

Results

A ...

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Long‐term chemogenetic suppression of seizures in a multifocal rat model of temporal lobe epilepsy

Summary

Objective

One third of epilepsy patients do not become seizure‐free using conventional medication. Therefore, there is a need for alternative treatments. Preclinical research using designer receptors exclusively activated by designer drugs (DREADDs) has demonstrated initial success in suppressing epileptic activity. Here, we evaluated whether long‐term chemogenetic seizure suppression could be obtained in the intraperitoneal kainic acid rat model of temporal lobe epilepsy, when DREADDs were selectively expressed in excitatory hippocampal neurons.

Methods

Epileptic male Sprague Dawley rats received unilateral hippocampal injections of adeno‐associated ...

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Ictal activation of oxygen‐conserving reflexes as a mechanism for sudden death in epilepsy

Abstract

Objective

To test the hypothesis that death with physiological parallels to human cases of sudden unexpected death in epilepsy (SUDEP) can be induced in seizing rats by ictal activation of oxygen‐conserving reflexes (OCRs).

Methods

Urethane‐anesthetized female Long‐Evans rats were implanted with electrodes for electrocardiography (ECG), electrocorticography (ECoG), and respiratory thermocouple; venous and arterial cannulas; and a laryngoscope guide and cannula or nasal cannula for activation of the laryngeal chemoreflex (LCR) or mammalian diving reflex (MDR), respectively. Kainic acid injection, either systemic or into ...

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Detection of covert lesions in focal epilepsy using computational analysis of multimodal magnetic resonance imaging data

Abstract

Objective

To compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans.

Methods

We developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI‐visible lesions. ...

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Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial

Abstract

Objective

This study was undertaken to describe patterns of benzodiazepine use as first‐line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second‐line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT).

Methods

Patients refractory to an adequate dose of benzodiazepines for the treatment of SE were enrolled in ESETT. Choice of benzodiazepine, doses given prior to administration of second‐line agent, route of administration, setting, and patient weight were characterized. These were compared with ...

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