The use of lamotrigine, vigabatrin and gabapentin as add-on therapy in intractable epilepsy of childhood

McDonald, Denise; Najam, Yawar; Keegan, Maria; Whooley, Max; Madden, David; McMenamin, Joseph B.

doi:10.1016/j.seizure.2004.12.001

Cited by 16 publications

(7 citation statements)

References 6 publications

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“…17 The retrospective clinical chart review of 26 children on gabapentin add-on therapy did not find any cases of rash associated with gabapentin use. 8 Finally, in a postmarketing surveillance study, reports on 136 children younger than 12 years of age were received. Six of these children had developed rash, but in only 2 cases (1.5%) was this thought to be due to gabapentin therapy and severe enough to discontinue the drug.…”

Section: Discussionmentioning

confidence: 99%

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Probability of Rash Related to Gabapentin Therapy in a Child

2009

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Section: Discussionmentioning

confidence: 99%

“…1,3-6 Rash is considered an uncommon effect of gabapentin administration in children, in contrast to lamotrigine, for which rash is reported in up to 10% of adults and children. 7, 8 We describe a child who developed a skin reaction shortly after starting gabapentin therapy and evaluate the probability that this reaction was related to gabapentin.…”

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confidence: 99%

Probability of Rash Related to Gabapentin Therapy in a Child

2009

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“…In addition to its ATP dependent ion channels modulation properties, LMT might promote mitochondrial stability through its anti oxidant (39), anti excitotoxic (40) and anti apoptotic effects (41). LMT might also carry additional properties on the mitochondrial membrane permeability and/or the respiratory chain complexes activity, which have not been reported yet.…”

Section: Discussionmentioning

confidence: 99%

Lamotrigine Is Neuroprotective in the Energy Deficiency Model of MPTP Intoxicated Mice

et al. 2007

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ABSTRACT:The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibits the mitochondrial complex I of the respiratory chain. This results in ATP and ion homeostasis disturbances, which lead to selective death of the substantia nigra dopaminergic neurons. Well known as a Parkinson's disease model, the MPTP animal model also provides a potential paradigm of the energy deficiencies found in childhood. In these conditions, anticonvulsants may provide neuroprotection by limiting cellular energy consumption. We tested valproate, topiramate and lamotrigine in the MPTP mouse model. Dopamine transporter (DAT) density was assessed by quantitative autoradiography, tyrosine hydroxylase (TH) was evaluated by immunohistochemistry and dopamine (DA) levels by HPLC-ED whereas neuronal apoptosis was monitored through active caspase-3. Expectedly, the DAT density, TH immunoreactive neurons and DA content in the MPTP group were respectively reduced to 51%, 40% and 26% versus control animals. Unlike valproate and topiramate, lamotrigine provided a significant neuroprotection against MPTP in maintaining these levels at 99%, 74% and 58% respectively and reducing the induced apoptosis. Altogether, the data indicate that lamotrigine limits dopaminergic neuronal death in the substantia nigra and promotes striatal dendrites sprouting. Lamotrigine, a widely used and well-tolerated molecule in young patients, could represent a valuable adjuvant therapy in various energy deficiency conditions during childhood. (Pediatr Res 62: 14-19, 2007) E vidences from degenerative and metabolic encephalopathies studies indicate that the striatum and the substantia nigra (SN) are vulnerable structures in the brain, especially during pre and postnatal brain development (1,2). A partial or total destruction of this striato-nigral dopaminergic network is found in several conditions occurring in childhood such as iron or copper metabolism abnormalities (1), organic acidurias (3), urea cycle disorders, various mitochondrial energy production deficiencies (1,4), or hypoxia-ischemia (2,5). All these conditions witness the vulnerability of this particular deep nuclei network involved in multiple motor, sensory and cognitive functions.These basal ganglia share a common susceptibility to energetic stress (6,7), which can be studied experimentally using mitochondrial inhibitors (8). Once converted into MPPϩ, the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibits the mitochondrial electron transport chain at complex I (NADH-ubiquinone oxidoreductase) resulting in decreased oxygen consumption and ATP production and ion homeostasis disturbances which, together, lead to neuronal cell death (9). This toxin depletes dopaminergic neurons in the SN and causes neuronal degeneration of the nigrostriatal pathway in animals and humans (9).Several neuroprotection studies were performed in this MPTP mouse model using: energy sparing drugs; free radicals scavengers; anti-glutamatergic drugs; anti-apoptotic molecules and neurotrophines (10 -12).Anticonvulsan...

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“…Most treatment regimens for SSADH-deficient patients have been symptomatic (e.g., treating seizures, aggressive behavior, etc). The most widely employed therapy has been vigabatrin, the irreversible GABA-transaminase inhibitor (35). Treatment with vigabatrin should result in decreased GHB production with increased GABA levels (Fig.…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Murine succinate semialdehyde dehydrogenase (SSADH) deficiency, a heritable disorder of GABA metabolism with epileptic phenotype

Gibson

Jakobs

Pearl

et al. 2005

IUBMB Life (International Union of Biochemistry and Molecular B

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Murine models of inborn errors of metabolism represent an established approach for investigating pathophysiological mechanisms associated with the corresponding human disorder. Our laboratory studies human inherited defects of GABA synthesis and degradation. One of these, succinate semialdehyde dehydrogenase (SSADH) deficiency (or gamma-hydroxybutyric aciduria; OMIM 271980; E.C. 1.2.1.24), has recently been modeled via gene targeting in the mouse. SSADH-/- mice succumb to early lethality in status epilepticus at postnatal (PN) days 20 - 26. Numerous metabolic, neurochemical and neurophysiological abnormalities have been documented using in vitro and in vivo approaches, substantially altering our thoughts about the complexity of the corresponding human condition. Moreover, novel preclinical treatment paradigms have been developed through drug trials in gene-ablated animals. The greatest utility of this animal, however, may reside in its transition from early absence seizures to generalized convulsions and eventual status epilepticus. Accurate neurochemical assessment during this transition may provide clues to the same transition process in patients, for which the underlying mechanisms remain undefined.

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The use of lamotrigine, vigabatrin and gabapentin as add-on therapy in intractable epilepsy of childhood

Abstract: Lamotrigine is a useful add-on therapy in treating children with epilepsy. It has a low adverse event profile and a sustained beneficial effect in children with intractable epilepsy.

Cited by 16 publications

References 6 publications

Probability of Rash Related to Gabapentin Therapy in a Child

Probability of Rash Related to Gabapentin Therapy in a Child

Lamotrigine Is Neuroprotective in the Energy Deficiency Model of MPTP Intoxicated Mice

Murine succinate semialdehyde dehydrogenase (SSADH) deficiency, a heritable disorder of GABA metabolism with epileptic phenotype

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