Experimental Convulsions Induced by Administration of Thujone

Keith, H. M.; Stavraky, G. W.; Rogerson, C. H.; Hardcastle, D. H.; Duguid, K.

doi:10.1097/00005053-193607000-00020

Cited by 8 publications

(9 citation statements)

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“…It has, thus, been hypothesised that the ketone bodies play a crucial role in the antiepileptic properties seen in KD. Studies involving administration of acetone and acetoacetate in animal models including rabbits, mice and rats have shown protection against induced seizures to varying degrees (45)(46)(47)(48) . In our study, we showed MCTD-related antiepileptic effects that were poorly correlated with relative changes in serum BHB concentrations.…”

Section: Discussionmentioning

confidence: 99%

A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy

Law

Davies

Pan³

et al. 2015

Br J Nutr

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Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0–9·89/month) in comparison with the placebo diet (2·67/month, 0·33–22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68–43·27 %) and six showed no response. Seizure day frequency were also significantly lower when dogs were fed the MCTD (1·63/month, 0–7·58/month) in comparison with the placebo diet (1·69/month, 0·33–13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood β-hydroxybutyrate concentrations in comparison with placebo diet (0·041 (sd 0·004) v. 0·031 (sd 0·016) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment.

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Section: Discussionmentioning

confidence: 99%

A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy

Law

Davies

Pan³

et al. 2015

Br J Nutr

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“…In trying to understand a ketogenic diet’s therapeutic mechanism, many laboratories have investigated whether ketone bodies at pharmacological doses have intrinsic anticonvulsant properties. The anticonvulsant properties of acetoacetate were first reported by Keith (1935) where its administration in rabbits protected against thujone‐induced seizures. In agreement with this early report, Rho and colleagues found that intraperitoneally administered acetoacetate and acetone, but not β‐hydroxybutyrate, protected against seizures in the Frings audiogenic seizure‐susceptible juvenile mouse (Rho et al.…”

Section: Ketone Bodies: Anticonvulsant Propertiesmentioning

confidence: 99%

Ketone bodies in epilepsy

McNally

Hartman

2012

Journal of Neurochemistry

171

134

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Seizures that are resistant to standard medications remain a major clinical problem. One underutilized option for patients with medication-resistant seizures is the high-fat, low-carbohydrate ketogenic diet. The diet received its name based on the observation that patients consuming this diet produce ketone bodies (e.g., acetoacetate, β-hydroxybutyrate, and acetone). Although the exact mechanisms of the diet are unknown, ketone bodies have been hypothesized to contribute to the anticonvulsant and antiepileptic effects. In this review, anticonvulsant properties of ketone bodies and the ketogenic diet are discussed (including GABAergic and glutamatergic effects). Because of the importance of ketone body metabolism in the early stages of life, the effects of ketone bodies on developing neurons in vitro also are discussed. Understanding how ketone bodies exert their effects will help optimize their use in treating epilepsy and other neurological disorders.

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“…Studies dating back to the 1930s also support the direct antiseizure effects of ketones [15,16]. In mice, acetone and acetoacetate raise seizure thresholds, resulting in fewer seizures [15,16]. Although BHB did not appear to contribute to antiseizure effects in these earlier studies, more recent studies indicate that BHB probably does play a direct antiseizure role, and that its effects may have been previously missed for methodological reasons [11].…”

Section: Ketones As Key Mediators Of Seizure Controlmentioning

confidence: 86%

Section: Ketones As Key Mediators Of Seizure Controlmentioning

confidence: 94%

Ketogenic Diet Therapies in Children and Adults with Epilepsy

Phillips¹

2019

Epilepsy - Advances in Diagnosis and Therapy

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Despite a wide array of anti-epileptic drugs and the option of surgery, one-third of children and adults with epilepsy continue to suffer from drug-resistant seizures. Many of these patients may benefit from a ketogenic diet, a non-pharmacologic therapy proven to improve seizure control in epilepsy. Ketogenic diets aim to mimic the metabolic profile of fasting, and probably improve seizure control through a variety of mechanisms that collectively stabilize synaptic function. Although many similarities exist with regards to patient selection, patient preparation, and diet implementation in children compared to adults, there are also important differences. The most conspicuous challenge to the more widespread use of ketogenic diets in children and adults with epilepsy is a lack of access to ketogenic services in many regions of the world. Moreover, the culinary and social restrictions associated with conventional ketogenic diets pose a significant barrier to their use in adults.

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Experimental Convulsions Induced by Administration of Thujone

Cited by 8 publications

References 0 publications

A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy

A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy

Ketone bodies in epilepsy

Ketogenic Diet Therapies in Children and Adults with Epilepsy

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