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Archives of Disease in Childhood Apr 2005Corticosteroids (predominantly prednisolone and hydrocortisone) and adrenocorticotropic hormone (ACTH) have been used in the treatment of the epilepsies for over 50... (Review)
Review
Corticosteroids (predominantly prednisolone and hydrocortisone) and adrenocorticotropic hormone (ACTH) have been used in the treatment of the epilepsies for over 50 years. Over the past 30 years most reports have focused on epilepsy syndromes and epileptic encephalopathies resistant to treatment with the more conventional anticonvulsant and antiepileptic drugs (AEDs) and specifically West syndrome. There has been relatively little attention on the role of corticosteroids in treating other epilepsies.
Topics: Adrenal Cortex Hormones; Anticonvulsants; Child; Epilepsy; Humans; Infant; Spasms, Infantile; Syndrome
PubMed: 15781928
DOI: 10.1136/adc.2004.051375 -
The Cochrane Database of Systematic... May 2016July 2015: This review has been split and updated in a series of four new reviews (Linde 2013a; Linde 2013b; Linde 2013c; Linde 2013d). Readers are referred to those... (Meta-Analysis)
Meta-Analysis Review
July 2015: This review has been split and updated in a series of four new reviews (Linde 2013a; Linde 2013b; Linde 2013c; Linde 2013d). Readers are referred to those reviews for updated results. This review will not be updated. May 2016: This review has now been withdrawn as it has been replaced by the four new titles listed above. The editorial group responsible for this previously published document have withdrawn it from publication.
Topics: Adult; Anticonvulsants; Humans; Migraine Disorders; Randomized Controlled Trials as Topic
PubMed: 27233055
DOI: 10.1002/14651858.CD003226.pub3 -
Journal of Neuroscience Research Jan 2017Epilepsy is one of the leading causes of chronic neurological morbidity worldwide. Acquired epilepsy may result from a number of conditions, such as brain injury,... (Review)
Review
Epilepsy is one of the leading causes of chronic neurological morbidity worldwide. Acquired epilepsy may result from a number of conditions, such as brain injury, anoxia, tumors, stroke, neurotoxicity, and prolonged seizures. Sex differences have been observed in many seizure types; however, some sex-specific seizure disorders are much more prevalent in women. Despite some inconsistencies, substantial data indicates that sensitivity to seizure stimuli differs between the sexes. Men generally exhibit greater seizure susceptibility than women, whereas many women with epilepsy experience a cyclical occurrence of seizures that tends to center around the menstrual period, which has been termed catamenial epilepsy. Some epilepsy syndromes show gender differences with female predominance or male predominance. Steroid hormones, endogenous neurosteroids, and sexually dimorphic neural networks appear to play a key role in sex differences in seizure susceptibility. Neurosteroids, such as allopregnanolone, reflect sex differences in their anticonvulsant activity. This Review provides a brief overview of the evidence for sex differences in epilepsy and how sex differences influence the use of neurosteroids in epilepsy and epileptogenesis. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Anticonvulsants; Epilepsy; Humans; Neurotransmitter Agents; Sex Characteristics
PubMed: 27870400
DOI: 10.1002/jnr.23853 -
Current Neuropharmacology 2021Over the decades, various interventions have been developed and utilized to treat epilepsy. However, the majority of epileptic patients are often first prescribed... (Review)
Review
Over the decades, various interventions have been developed and utilized to treat epilepsy. However, the majority of epileptic patients are often first prescribed anti-epileptic drugs (AED), now known as anti-seizure drugs (ASD), as the first line of defense to suppress their seizures and regain their quality of life. ASDs exert their anti-convulsant effects through various mechanisms of action, including regulation of ion channels, blocking glutamate-mediated stimulating neurotransmitter interaction, and enhancing the inhibitory GABA transmission. About one-third of epileptic patients are often resistant to anti-convulsant drugs, while others develop numerous side effects, which may lead to treatment discontinuation and further deterioration of quality of life. Common side effects of ASDs include headache, nausea and dizziness. However, more adverse effects, such as auditory and visual problems, skin problems, liver dysfunction, pancreatitis and kidney disorders may also be witnessed. Some ASDs may even result in life-threatening conditions as well as serious abnormalities, especially in patients with comorbidities and in pregnant women. Nevertheless, some clinicians had observed a reduction in the development of side effects post individualized ASD treatment. This suggests that a careful and well-informed ASD recommendation to patients may be crucial for an effective and side-effect-free control of their seizures. Therefore, this review aimed to elucidate the anticonvulsant effects of ASDs as well as their side effect profile by discussing their mechanism of action and reported adverse effects based on clinical and preclinical studies, thereby providing clinicians with a greater understanding of the safety of current ASDs.
Topics: Anticonvulsants; Epilepsy; Female; Humans; Pharmaceutical Preparations; Pregnancy; Quality of Life; Seizures
PubMed: 34525933
DOI: 10.2174/1570159X19666210826125341 -
Current Neuropharmacology 2018Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in... (Review)
Review
BACKGROUND
Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in recent years, recurrent epileptic seizures remain intractable and lead to a serious morbidity in the world. The ketogenic diet refers to a high-fat, low-carbohydrate and adequate-protein diet. Currently, its beneficial effects on epileptic seizure reduction have been well established. However, the detailed mechanisms underlying the anti-epileptic effects of ketogenic diet are still poorly understood. In this article, the possible roles of ketogenic diet on epilepsy were discussed.
METHODS
Data was obtained from the websites including Web of Science, Medline, Pubmed, Scopus, based on these keywords: "Ketogenic diet" and "epilepsy".
RESULTS
As shown in both clinical and basic studies, the therapeutic effects of ketogenic diet might involve neuronal metabolism, neurotransmitter function, neuronal membrane potential and neuron protection against ROS.
CONCLUSION
In this review, we systematically reviewed the effects and possible mechanisms of ketogenic diet on epilepsy, which may optimize the therapeutic strategies against epilepsy.
Topics: Animals; Anticonvulsants; Diet, Ketogenic; Humans; Seizures
PubMed: 28521671
DOI: 10.2174/1570159X15666170517153509 -
Advances in Therapy Apr 2024Stiripentol (Diacomit) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet... (Review)
Review
Stiripentol (Diacomit) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet syndrome (DS), a severe form of childhood epilepsy, in conjunction with clobazam and, in some regions valproic acid. Since the discovery of STP, several mechanisms of action (MoA) have been described that may explain its specific effect on seizures associated with DS. STP is mainly considered as a potentiator of gamma-aminobutyric acid (GABA) neurotransmission: (i) via uptake blockade, (ii) inhibition of degradation, but also (iii) as a positive allosteric modulator of GABA receptors, especially those containing α3 and δ subunits. Blockade of voltage-gated sodium and T-type calcium channels, which is classically associated with anticonvulsant and neuroprotective properties, has also been demonstrated for STP. Finally, several studies indicate that STP could regulate glucose energy metabolism and inhibit lactate dehydrogenase. STP is also an inhibitor of several cytochrome P450 enzymes involved in the metabolism of other ASMs, contributing to boost their anticonvulsant efficacy as add-on therapy. These different MoAs involved in treatment of DS and recent data suggest a potential for STP to treat other neurological or non-neurological diseases.
Topics: Humans; Anticonvulsants; Dioxolanes; Seizures; Epilepsies, Myoclonic; gamma-Aminobutyric Acid
PubMed: 38443647
DOI: 10.1007/s12325-024-02813-0 -
Molecules (Basel, Switzerland) Dec 2021Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and... (Review)
Review
Valproic acid (VPA) is a well-established anticonvulsant drug discovered serendipitously and marketed for the treatment of epilepsy, migraine, bipolar disorder and neuropathic pain. Apart from this, VPA has potential therapeutic applications in other central nervous system (CNS) disorders and in various cancer types. Since the discovery of its anticonvulsant activity, substantial efforts have been made to develop structural analogues and derivatives in an attempt to increase potency and decrease adverse side effects, the most significant being teratogenicity and hepatotoxicity. Most of these compounds have shown reduced toxicity with improved potency. The simple structure of VPA offers a great advantage to its modification. This review briefly discusses the pharmacology and molecular targets of VPA. The article then elaborates on the structural modifications in VPA including amide-derivatives, acid and cyclic analogues, urea derivatives and pro-drugs, and compares their pharmacological profile with that of the parent molecule. The current challenges for the clinical use of these derivatives are also discussed. The review is expected to provide necessary knowledgebase for the further development of VPA-derived compounds.
Topics: Amides; Animals; Anticonvulsants; Drug Monitoring; Epilepsy; Humans; Molecular Structure; Structure-Activity Relationship; Teratogens; Urea; Valproic Acid
PubMed: 35011339
DOI: 10.3390/molecules27010104 -
American Journal of Medical Genetics.... Aug 2012The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy (WWE) require anticonvulsant drugs for adequate... (Review)
Review
The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy (WWE) require anticonvulsant drugs for adequate control of their seizures, the teratogenicity associated with some antiepileptic drugs (AEDs) is a risk that needs to be carefully addressed. Antiepileptic medications are also used to treat an ever broadening range of medical conditions such as bipolar disorder, migraine prophylaxis, cancer, and neuropathic pain. Despite the fact that the majority of pregnancies of WWE who are receiving pharmacological treatment are normal, studies have demonstrated that the risk of having a pregnancy complicated by a major congenital malformation is doubled when comparing the risk of untreated pregnancies. Furthermore, when AEDs are used in polytherapy regimens, the risk is tripled, especially when valproic acid (VPA) is included. However, it should be noted that the risks are specific for each anticonvulsant drug. Some investigations have suggested that the risk of teratogenicity is increased in a dose-dependent manner. More recent studies have reported that in utero exposure to AEDs can have detrimental effects on the cognitive functions and language skills in later stages of life. In fact, the FDA just issued a safety announcement on the impact of VPA on cognition (Safety Announcement 6-30-2011). The purpose of this document is to review the most commonly used compounds in the treatment of WWE, and to provide information on the latest experimental and human epidemiological studies of the effects of AEDs in the exposed embryos.
Topics: Anticonvulsants; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 22711424
DOI: 10.1002/ajmg.a.35438 -
Epilepsia Nov 2008Recent interest in the anticonvulsant effects of acetone has stemmed from studies related to the ketogenic diet (KD). The KD, a high-fat diet used to treat... (Review)
Review
Recent interest in the anticonvulsant effects of acetone has stemmed from studies related to the ketogenic diet (KD). The KD, a high-fat diet used to treat drug-resistant seizures, raises blood and brain levels of three ketones: beta-hydroxybutyrate, acetoacetate, and acetone. An obvious question is whether these ketones have anticonvulsant properties. We found that neither beta-hydroxybutyrate nor acetoacetate has proven to be anticonvulsant. Acetone, however, is clearly anticonvulsant at physiological, and near-physiological, nontoxic concentrations. Despite knowledge of acetone's anticonvulsant properties since the 1930's, acetone had never been characterized using the standard animal seizure tests. In our recent experiments, acetone was found to be active in animal models of tonic-clonic seizures, typical absence seizures, complex partial seizures, and atypical absence seizures associated with Lennox-Gastaut syndrome. Therapeutic indices are either comparable or better than that of valproate, a standard broad-spectrum anticonvulsant. A number of acetone-like molecules have also been tested, and these also show good potency up to a "cutoff" point of nine carbons contained in the side chain. Above this number, potency disappears, suggesting the possibility of a receptor for acetone and its analogs.
Topics: Acetone; Animals; Anticonvulsants; Diet, Ketogenic; Humans; Ketone Bodies; Seizures
PubMed: 19049597
DOI: 10.1111/j.1528-1167.2008.01844.x -
Cells Jun 2023Zebrafish (Danio rerio) assays provide a versatile pharmacological platform to test compounds on a wide range of behaviors in a whole organism. A major challenge lies in...
Zebrafish (Danio rerio) assays provide a versatile pharmacological platform to test compounds on a wide range of behaviors in a whole organism. A major challenge lies in the lack of knowledge about the bioavailability and pharmacodynamic effects of bioactive compounds in this model organism. Here, we employed a combined methodology of LC-ESI-MS/MS analytics and targeted metabolomics with behavioral experiments to evaluate the anticonvulsant and potentially toxic effects of the angular dihydropyranocoumarin pteryxin (PTX) in comparison to the antiepileptic drug sodium valproate (VPN) in zebrafish larvae. PTX occurs in different Apiaceae plants traditionally used in Europe to treat epilepsy but has not been investigated so far. To compare potency and efficacy, the uptake of PTX and VPN into zebrafish larvae was quantified as larvae whole-body concentrations together with amino acids and neurotransmitters as proxy pharmacodynamic readout. The convulsant agent pentylenetetrazole (PTZ) acutely reduced the levels of most metabolites, including acetylcholine and serotonin. Conversely, PTX strongly reduced neutral essential amino acids in a LAT1 (SLCA5)-independent manner, but, similarly to VPN specifically increased the levels of serotonin, acetylcholine, and choline, but also ethanolamine. PTX dose and time-dependent manner inhibited PTZ-induced seizure-like movements resulting in a ~70% efficacy after 1 h at 20 µM (the equivalent of 4.28 ± 0.28 µg/g in larvae whole-body). VPN treated for 1 h with 5 mM (the equivalent of 18.17 ± 0.40 µg/g in larvae whole-body) showed a ~80% efficacy. Unexpectedly, PTX (1-20 µM) showed significantly higher bioavailability than VPN (0.1-5 mM) in immersed zebrafish larvae, possibly because VPN in the medium dissociated partially to the readily bioavailable valproic acid. The anticonvulsive effect of PTX was confirmed by local field potential (LFP) recordings. Noteworthy, both substances specifically increased and restored whole-body acetylcholine, choline, and serotonin levels in control and PTZ-treated zebrafish larvae, indicative of vagus nerve stimulation (VNS), which is an adjunctive therapeutic strategy to treat refractory epilepsy in humans. Our study demonstrates the utility of targeted metabolomics in zebrafish assays and shows that VPN and PTX pharmacologically act on the autonomous nervous system by activating parasympathetic neurotransmitters.
Topics: Humans; Animals; Pentylenetetrazole; Valproic Acid; Zebrafish; Vagus Nerve Stimulation; Serotonin; Acetylcholine; Tandem Mass Spectrometry; Seizures; Anticonvulsants; Choline
PubMed: 37296660
DOI: 10.3390/cells12111540