Pharmacological treatment of childhood absence epilepsy

Posner, Ewa

doi:10.1586/14737175.6.6.855

Cited by 20 publications

(18 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, the pharmacological treatment of G1D seizures is generally ineffective. A potential role for several specific anticonvulsants was suggested by the spike-wave EEG pattern often identified in G1D seizures, which is typical of some absence epilepsies 5152 . Yet this approach has proven ineffective 16 .…”

Section: Commentmentioning

confidence: 99%

Triheptanoin for Glucose Transporter Type I Deficiency (G1D)

et al. 2014

View full text Add to dashboard Cite

IMPORTANCE Disorders of brain metabolism are multiform in their mechanisms and manifestations, many of which remain insufficiently understood and are thus similarly treated. Glucose transporter type I deficiency (G1D) is commonly associated with seizures and with electrographic spike-waves. The G1D syndrome has long been attributed to energy (ie, adenosine triphosphate synthetic) failure such as that consequent to tricarboxylic acid (TCA) cycle intermediate depletion. Indeed, glucose and other substrates generate TCAs via anaplerosis. However, TCAs are preserved in murine G1D, rendering energy-failure inferences premature and suggesting a different hypothesis, also grounded on our work, that consumption of alternate TCA precursors is stimulated and may be detrimental. Second, common ketogenic diets lead to a therapeutically counterintuitive reduction in blood glucose available to the G1D brain and prove ineffective in one-third of patients.OBJECTIVE To identify the most helpful outcomes for treatment evaluation and to uphold (rather than diminish) blood glucose concentration and stimulate the TCA cycle, including anaplerosis, in G1D using the medium-chain, food-grade triglyceride triheptanoin. DESIGN, SETTING, AND PARTICIPANTSUnsponsored, open-label cases series conducted in an academic setting. Fourteen children and adults with G1D who were not receiving a ketogenic diet were selected on a first-come, first-enrolled basis.INTERVENTION Supplementation of the regular diet with food-grade triheptanoin. MAIN OUTCOMES AND MEASURESFirst, we show that, regardless of electroencephalographic spike-waves, most seizures are rarely visible, such that perceptions by patients or others are inadequate for treatment evaluation. Thus, we used quantitative electroencephalographic, neuropsychological, blood analytical, and magnetic resonance imaging cerebral metabolic rate measurements.RESULTS One participant (7%) did not manifest spike-waves; however, spike-waves promptly decreased by 70% (P = .001) in the other participants after consumption of triheptanoin. In addition, the neuropsychological performance and cerebral metabolic rate increased in most patients. Eleven patients (78%) had no adverse effects after prolonged use of triheptanoin. Three patients (21%) experienced gastrointestinal symptoms, and 1 (7%) discontinued the use of triheptanoin. CONCLUSIONS AND RELEVANCETriheptanoin can favorably influence cardinal aspects of neural function in G1D. In addition, our outcome measures constitute an important framework for the evaluation of therapies for encephalopathies associated with impaired intermediary metabolism.

show abstract

Section: Commentmentioning

confidence: 99%

Triheptanoin for Glucose Transporter Type I Deficiency (G1D)

et al. 2014

View full text Add to dashboard Cite

show abstract

“…However, reduced Scn8a activity also leads to non-convulsive absence epilepsy in mice (Papale et al, 2009) and humans (Berghuis et al, 2015). Similarly, common antiepileptic drugs (AEDs) that act on VGSCs are known to effectively control generalized convulsive and partial epilepsies; however, they are often ineffective against absence seizures and may even increase the risk of absence epilepsy (Manning et al, 2003; Osorio et al, 2000; Posner, 2006). …”

Section: Introductionmentioning

confidence: 99%

Regulation of Thalamic and Cortical Network Synchrony by Scn8a

Makinson

Tanaka

Sorokin

et al. 2017

Neuron

102

129

View full text Add to dashboard Cite

SUMMARYVoltage-gated sodium channel (VGSC) mutations cause severe epilepsies marked by intermittent, pathological hypersynchronous brain states. Here we present two mechanisms that help to explain how mutations in one VGSC gene, Scn8a, contribute to two distinct seizure phenotypes: (1) hypoexcitation of cortical circuits leading to convulsive seizure resistance, and (2) hyperexcitation of thalamocortical circuits leading to non-convulsive absence epilepsy. We found that loss of Scn8a leads to altered RT cell intrinsic excitability and a failure in recurrent RT synaptic inhibition. We propose that these deficits cooperate to enhance thalamocortical network synchrony and generate pathological oscillations. To our knowledge, this finding is the first clear demonstration of a pathological state tied to disruption of the RT-RT synapse. Our observation that loss of a single gene in the thalamus of an adult wild-type animal is sufficient to cause spike-wave discharges is striking and represents an example of absence epilepsy of thalamic origin.

show abstract

“…3 Childhood absence epilepsy is an idiopathic, age-related epilepsy syndrome notable for multiple daily staring spells and occasional generalized tonic-clonic seizures. 5 Childhood absence epilepsy is initially treated with anticonvulsants, most commonly ethosuximide, valproate, and lamotrigine. 5 Juvenile absence epilepsy begins in early adolescence and is more likely to be associated with generalized tonic-clonic seizures.…”

mentioning

confidence: 99%

“…5 Childhood absence epilepsy is initially treated with anticonvulsants, most commonly ethosuximide, valproate, and lamotrigine. 5 Juvenile absence epilepsy begins in early adolescence and is more likely to be associated with generalized tonic-clonic seizures. 6 Treatments for juvenile absence epilepsy are also usually anticonvulsants, often valproate, lamotrigine, and topiramate.…”

mentioning

confidence: 99%

Do Patients With Absence Epilepsy Respond to Ketogenic Diets?

et al. 2010

View full text Add to dashboard Cite

Dietary therapies are established as beneficial for symptomatic generalized epilepsies such as Lennox-Gastaut syndrome; however, the outcome for idiopathic generalized epilepsy has never been specifically reported. The efficacy of the ketogenic and modified Atkins diet for childhood and juvenile absence epilepsy was evaluated from both historical literature review and patients treated at Johns Hopkins Hospital. Upon review of 17 published studies in which absence epilepsy was included as a patient subpopulation, approximately 69% of 133 with clear outcomes patients who received the ketogenic diet had a >50% seizure reduction, and 34% of these patients became seizure free. At Johns Hopkins Hospital, the ketogenic diet (n = 8) and modified Atkins diet (n = 13) led to similar outcomes, with 18 (82%) having a >50% seizure reduction, of which 10 (48%) had a >90% seizure reduction and 4 (19%) were seizure free. Neither age at diet onset, number of anticonvulsants used previously, particular diet used, nor gender correlated with success.

show abstract

Pharmacological treatment of childhood absence epilepsy

Cited by 20 publications

References 59 publications

Triheptanoin for Glucose Transporter Type I Deficiency (G1D)

Triheptanoin for Glucose Transporter Type I Deficiency (G1D)

Regulation of Thalamic and Cortical Network Synchrony by Scn8a

Do Patients With Absence Epilepsy Respond to Ketogenic Diets?

Contact Info

Product

Resources

About