Is Infantile Alternating Hemiplegia Mediated by Glutamate Toxicity and Can it be Treated with Memantine?

Korinthenberg, R

doi:10.1055/s-2007-973779

Cited by 9 publications

(8 citation statements)

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“…Other drugs that induce sleep such as chloral hydrate and niaprazine also was used [9]. Korinthenberg reported a patient who was resistant to flunarizine responded to memantine [10]. Sone reported the use of amantadine in two patients with AHC [11].…”

Section: Discussionmentioning

confidence: 99%

Topiramate: A new Agent for Patients with Alternating Hemiplegia of Childhood

Jiang

Chi²,

Ma³

et al. 2006

Neuropediatrics

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Alternating hemiplegia of childhood is a rare syndrome characterized by the onset, before 18 months of age, of frequent attacks of alternating paralysis. Here we report the efficacy of topiramate in four patients with alternating hemiplegia of childhood (AHC) that did not respond to flunarizine, as well as in two newly diagnosed patients. Following treatment with topiramate, the frequency and duration of hemiplegic attacks significantly improved in all patients. Additional symptoms such as seizures, migraine, involuntary movements, autonomic symptoms, and impaired mental development also improved. Topiramate is worth trying when treating patients with AHC as a first trial, or a substitute for flunarizine once the latter agent loses effect.

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Section: Discussionmentioning

confidence: 99%

Topiramate: A new Agent for Patients with Alternating Hemiplegia of Childhood

Jiang

Chi²,

Ma³

et al. 2006

Neuropediatrics

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“…Although memantine has never been widely used for Parkinson's disease, it was registered in Germany in 1978 and became popular as an all-purpose neurological tonic, with anecdotal reports of utility in dementia, organic brain syndrome, acquired pendular nystagmus in multiple sclerosis (139), neurogenic bladder (57), alternating hemiplegia of childhood (71), neuroleptic drug-induced adverse reactions, spasticity and even coma (98). In 1989, memantine officially was launched in Germany for use in the treatment of dementia.…”

Section: Introductionmentioning

confidence: 99%

The Neuropharmacological Basis for the Use of Memantine in the Treatment of Alzheimer's Disease

2003

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Memantine has been demonstrated to be safe and effective in the symptomatic treatment of Alzheimer's disease (AD). While the neurobiological basis for the therapeutic activity of memantine is not fully understood, the drug is not a cholinesterase in-hibitor and, therefore, acts differently from current AD therapies. Memantine can interact with a variety of ligand-gated ion channels. However, NMDA receptors appear to be a key target of memantine at therapeutic concentrations. Memantine is an uncompetitive (channel blocking) NMDA receptor antagonist. Like other NMDA receptor antagonists, memantine at high concentrations can inhibit mechanisms of synaptic plasticity that are believed to underlie learning and memory. However, at lower, clinically relevant concentrations memantine can under some circumstances promote synaptic plasticity and preserve or enhance memory in animal models of AD. In addition, memantine can protect against the excitotoxic destruction of cholinergic neurons. Blockade of NMDA receptors by memantine could theoretically confer disease-modifying activity in AD by inhibiting the "weak" NMDA receptor-dependent excitotoxicity that has been hypothesized to play a role in the progressive neuronal loss that underlies the evolving dementia. Moreover, recent in vitro studies suggest that memantine abrogates â-amyloid (Aâ) toxicity and possibly inhibits Aâ production. Considerable attention has focused on the investigation of theories to explain the better tolerability of memantine over other NMDA receptor antagonists , particularly those that act by a similar channel blocking mechanism such as dis-sociative anesthetic-like agents (phencyclidine, ketamine, MK-801). A variety of chan-275 nel-level factors could be relevant, including fast channel-blocking kinetics and strong voltage-dependence (allowing rapid relief of block during synaptic activity), as well as reduced trapping (permitting egress from closed channels). These factors may allow memantine to block channel activity induced by low, tonic levels of glutamate-an action that might contribute to symptomatic improvement and could theoretically protect against weak excitotoxicity-while sparing synaptic responses required for normal be-havioral functioning, cognition and memory.

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“…Korinthenberg first reported an 8-year old boy with AHC, whose attacks were resistant to flunarizine, but responded dramatically to memantine, a derivative of amantadine hydrochloride [5]. Memantine as well as amantadine is an antiparkinsonian drug, acting as a noncompetitive antagonist of NMDA receptor [6].…”

Section: Discussionmentioning

confidence: 99%

“…In this case, brain MR spectroscopic examination also showed an abnormal chemical shift of glutamate. These facts, together with developing evidence that glutamate and NMDA receptors influence the pathogenesis of AHC, caused him to conclude that glutamate toxicity plays a pathogenic role in AHC [5,7].…”

Section: Discussionmentioning

confidence: 99%

“…Treatments with anticonvulsant drugs and antimigraine drugs are at times partially effective, but their efficacy is usually temporal or transient [4, 8 ± 11]. Korinthenberg first reported that memantine hydrochloride dramatically reduced the attacks of hemiplegia in a child with AHC, for whom flunarizine hydrochloride, currently the most effective drug for this disorder, was not effective [5]. We describe here the efficacy of amantadine, which shares pharmacological properties with memantine, in two patients with AHC, whose attacks were resistant to flunarizine.…”

Section: Introductionmentioning

confidence: 99%

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Successful Trial of Amantadine Hydrochloride for Two Patients with Alternating Hemiplegia of Childhood

Sone

Oguni²,

Katsumori³

et al. 2000

Neuropediatrics

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We report here the efficacy of amantadine hydrochloride for two patients with alternating hemiplegia of childhood (AHC) that did not respond to flunarizine. Amantadine was administered to one patient at age one year and seven months and to the other at age 25 years. The frequencies and duration of the hemiplegic attacks significantly improved in both patients. However, the attacks gradually returned to the previous level after a significant reduction in seizures for three years in the younger patient with ongoing AHC. Our therapeutic results further support the hypothesis that glutamate and NMDA receptors are involved in inducing alternating hemiplegic attacks, because amantadine as well as its derivative, memantine, are clinically available non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, with neuroprotective effects. Amantadine is worth trying when treating patients with AHC as a first trial or a substitute for flunarizine once the latter agent looses effect.

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Is Infantile Alternating Hemiplegia Mediated by Glutamate Toxicity and Can it be Treated with Memantine?

Cited by 9 publications

References 0 publications

Topiramate: A new Agent for Patients with Alternating Hemiplegia of Childhood

Topiramate: A new Agent for Patients with Alternating Hemiplegia of Childhood

The Neuropharmacological Basis for the Use of Memantine in the Treatment of Alzheimer's Disease

Successful Trial of Amantadine Hydrochloride for Two Patients with Alternating Hemiplegia of Childhood

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