Advanced Treatments for Childhood Epilepsy Beyond Antiseizure Medications
ABSTRACT A substantial minority of children with epilepsy have continued seizures despite adequate trials of standard antiseizure medications. To maximize seizure control and thereby optimize their neurodevelopmental outcomes, alternate nonmedication therapies should be considered for these patients. Dietary therapies, including the ketogenic diet and its variations, have been available for years. With a recent resurgence in popularity and expansion of indications, these treatments can lead to freedom from seizures or a significantly reduced seizure burden for a large number of patients. For carefully selected individuals, resective epilepsy surgery may offer the best hope for a cure. For others, palliation may be achieved through additional surgical approaches, such as corpus callosotomy and multiple subpial transections, or through neurostimulation techniques, such as the vagus nerve stimulator. In this review, we present these nonmedication approaches to treatment-resistant childhood epilepsy, with attention to patient selection and the potential risks and benefits.
- SourceAvailable from: Marvin A Soriano-Ursúa
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- "Epilepsy, one of the most common neurological disorders, is characterized by recurrent spontaneous seizures (Newton and Garcia, 2012; Joshi et al., 2013). It is known that these seizures, like other problems related to the central nervous system (including pain, anxiety, depression, dementia and stroke), are characterized by an altered balance between excitatory and inhibitory neuronal functions (Takahashi and Niimi, 2009). "
ABSTRACT: The influx/efflux of calcium (Ca2+) ions through channels in cellular membranes plays a pivotal role in many physiological and physiopathological processes. Among these are those involved in the physiopathology of epileptic seizures. Hence, the control of permeability of ions through these channels is considered a strategy for the development of anticonvulsant drugs. According to the previous reports, dihydropyridine derivatives have proven to be Ca2+ channel blockers and have anticonvulsive properties, presumably by means of their action on L-type Ca2+ channels (LCCs). The aim of the present study was to determine the anticonvulsant effects of four bis-1,4-dihydropyridines (bis-DHPs) in male CF1 mice (25–30 g bw) using two experimental models: maximal electroshock (MES, which induces convulsions with an alternating current of 60 Hz) and pentylenetetrazole administration (PTZ, 90 mg/kg administered i.p.). Additionally, the binding mode was explored with a docking study on a 3-D model of an LCC. The four bis-DHPs herein tested showed a protective effect in relation to the number of convulsions induced by MES, the recovery time after a convulsion, and the duration of the tonic phase. However, only bis-DHPs 01–03 reduced the duration of the clonic phase, and these compounds also produced a significant protective effect against the convulsions induced by PTZ administration. This effect may be related to the interaction of bis-DHPs with a cluster of aromatic residues (Tyr1152, Tyr1463, and Phe1159) involved in blocking calcium flow, as suggested by docking studies.Medicinal Chemistry Research 12/2014; 23(12). DOI:10.1007/s00044-014-1083-0 · 1.61 Impact Factor
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- "In addition, it is worthwhile mentioning that a recent study by Juge et al. linked fasting and excitatory neurotransmission through Cl − -dependent regulation of VGLUT activity (Juge et al., 2010). The ketogenic diet is often used to control epilepsy (Joshi et al., 2013). Although fasting does not affect the activity of glutamate reuptake transporters (Bough et al., 2007), the vesicular transporters are possibly targeted by the ketone bodies, in particular acetoacetate and β-hydroxybutyrate, produced by this diet. "
ABSTRACT: The vesicular neurotransmitter transporters (VNTs) are small proteins responsible for packing synaptic vesicles with neurotransmitters thereby determining the amount of neurotransmitter released per vesicle through fusion in both neurons and glial cells. Each transporter subtype was classically seen as a specific neuronal marker of the respective nerve cells containing that particular neurotransmitter or structurally related neurotransmitters. More recently, however, it has become apparent that common neurotransmitters can also act as co-transmitters, adding complexity to neurotransmitter release and suggesting intriguing roles for VNTs therein. We will first describe the current knowledge on vesicular glutamate transporters (VGLUT1/2/3), the vesicular excitatory amino acid transporter (VEAT), the vesicular nucleotide transporter (VNUT), vesicular monoamine transporters (VMAT1/2), the vesicular acetylcholine transporter (VAChT) and the vesicular γ-aminobutyric acid (GABA) transporter (VGAT) in the brain. We will focus on evidence regarding transgenic mice with disruptions in VNTs in different models of seizures and epilepsy. We will also describe the known alterations and reorganizations in the expression levels of these VNTs in rodent models for temporal lobe epilepsy (TLE) and in human tissue resected for epilepsy surgery. Finally, we will discuss perspectives on opportunities and challenges for VNTs as targets for possible future epilepsy therapies.Frontiers in Cellular Neuroscience 08/2013; 7:139. DOI:10.3389/fncel.2013.00139 · 4.18 Impact Factor
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ABSTRACT: Vagal nerve stimulators (VNS) are surgically implantable medical devices which are approved by the food and drug administration (FDA) for treatment of medically refractory epilepsy in children. Two children with seizures disorders presented to the pediatric otolaryngology clinic with complaints of stridor and sleep apnea following implantation of VNS devices. Both children were evaluated with flexible laryngoscopy, direct laryngoscopy and bronchoscopy. The children were noted to have contraction of their vocal folds and supraglottis and the settings of their VNS were adjusted until no further contractions were noted. Each child had resolution of their symptoms following adjustment. Published by Elsevier Ireland Ltd.International Journal of Pediatric Otorhinolaryngology 11/2014; 79(2). DOI:10.1016/j.ijporl.2014.10.037 · 1.32 Impact Factor