Valproate Metabolites in Serum and Urine During Antiepileptic Therapy in Children with Infantile Spasms: Abnormal Metabolite Pattern Associated with Reversible Hepatotoxicity

Fisher, E.; Siemes, H.; Pund, R.; Wittfoht, W.; Nau, Heinz

doi:10.1111/j.1528-1157.1992.tb02301.x

Cited by 47 publications

(22 citation statements)

References 16 publications

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“…The other study reported cessation of spasms in 72% of children at 3 months' follow-up. 49 Nitrazepam. Two class IV retrospective case series met the inclusion criteria for analysis.…”

Section: Other Agents What Other Agents Have Been Evaluated For the mentioning

confidence: 99%

“…Two studies met the inclusion criteria for analysis; both were class IV uncontrolled prospective open-label studies. 49,50 Valproate dose ranged from 25 to 100 mg/kg/day. One study reported cessation of spasms in 73% and resolution of hypsarrhythmia in 91% of 22 children at 6 months' follow-up.…”

Section: Other Agents What Other Agents Have Been Evaluated For the mentioning

confidence: 99%

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Practice Parameter: Medical Treatment of Infantile Spasms

Weiss²,

et al. 2004

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Abstract-Objective:To determine the current best practice for treatment of infantile spasms in children. Methods: Database searches of MEDLINE from 1966 and EMBASE from 1980 and searches of reference lists of retrieved articles were performed. Inclusion criteria were the documented presence of infantile spasms and hypsarrhythmia. Outcome measures included complete cessation of spasms, resolution of hypsarrhythmia, relapse rate, developmental outcome, and presence or absence of epilepsy or an epileptiform EEG. One hundred fifty-nine articles were selected for detailed review. Recommendations were based on a four-tiered classification scheme. Results: Adrenocorticotropic hormone (ACTH) is probably effective for the short-term treatment of infantile spasms, but there is insufficient evidence to recommend the optimum dosage and duration of treatment. There is insufficient evidence to determine whether oral corticosteroids are effective. Vigabatrin is possibly effective for the short-term treatment of infantile spasm and is possibly also effective for children with tuberous sclerosis. Concerns about retinal toxicity suggest that serial ophthalmologic screening is required in patients on vigabatrin; however, the data are insufficient to make recommendations regarding the frequency or type of screening. There is insufficient evidence to recommend any other treatment of infantile spasms. There is insufficient evidence to conclude that successful treatment of infantile spasms improves the long-term prognosis. Conclusions: ACTH is probably an effective agent in the short-term treatment of infantile spasms. Vigabatrin is possibly effective. NEUROLOGY 2004;62:1668 -1681 West syndrome 1 is a unique, age-specific epilepsy of early infancy. Infantile spasms are distinct from myoclonic and tonic seizures.2 They are characterized by an initial contraction phase followed by a more sustained tonic phase. They can be divided into three types (flexor, extensor, and mixed flexor-extensor spasms), and they can also be asymmetrical.2 The EEG characteristically demonstrates hypsarrhythmia, and onset of spasms is frequently associated with neurodevelopmental regression. The incidence of infantile spasms is

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“…The other study reported cessation of spasms in 72% of children at 3 months' follow-up. 49 Nitrazepam. Two class IV retrospective case series met the inclusion criteria for analysis.…”

Section: Other Agents What Other Agents Have Been Evaluated For the mentioning

confidence: 99%

Section: Other Agents What Other Agents Have Been Evaluated For the mentioning

confidence: 99%

Practice Parameter: Medical Treatment of Infantile Spasms

Weiss²,

et al. 2004

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“…All previous and current studies were rated Class IV for treatment using valproic acid (VPA), 30 Sulthiame. One Class II randomized, double-blind, placebo-controlled study demonstrated a 30% responder rate to sulthiame vs placebo ( p ϭ 0.025) e7 ; this finding is not different from spontaneous remission rates at as early as 1 month from spasms onset as described in limited natural history studies.…”

Section: Other Agents What Other Agents Are As Effective As Acth Formentioning

confidence: 99%

Evidence-based guideline update: Medical treatment of infantile spasms [RETIRED]

Mackay²,

Weiss³

et al. 2012

Neurology

300

277

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Objective:To update the 2004 American Academy of Neurology/Child Neurology Society practice parameter on treatment of infantile spasms in children.Methods: MEDLINE and EMBASE were searched from 2002 to 2011 and searches of reference lists of retrieved articles were performed. Sixty-eight articles were selected for detailed review; 26 were included in the analysis. Recommendations were based on a 4-tiered classification scheme combining pre-2002 evidence and more recent evidence. Results:There is insufficient evidence to determine whether other forms of corticosteroids are as effective as adrenocorticotropic hormone (ACTH) for short-term treatment of infantile spasms. However, low-dose ACTH is probably as effective as high-dose ACTH. ACTH is more effective than vigabatrin (VGB) for short-term treatment of children with infantile spasms (excluding those with tuberous sclerosis complex). There is insufficient evidence to show that other agents and combination therapy are effective for short-term treatment of infantile spasms. Short lag time to treatment leads to better long-term developmental outcome. Successful short-term treatment of cryptogenic infantile spasms with ACTH or prednisolone leads to better long-term developmental outcome than treatment with VGB.Recommendations: Low-dose ACTH should be considered for treatment of infantile spasms.ACTH or VGB may be useful for short-term treatment of infantile spasms, with ACTH considered preferentially over VGB. Hormonal therapy (ACTH or prednisolone) may be considered for use in preference to VGB in infants with cryptogenic infantile spasms, to possibly improve developmental outcome. A shorter lag time to treatment of infantile spasms with either hormonal therapy or VGB possibly improves long-term developmental outcomes. Neurology ® 2012;78:1974-1980 GLOSSARY AAN ϭ American Academy of Neurology; ACTH ϭ adrenocorticotropic hormone; AE ϭ adverse effect; AED ϭ antiepileptic drug; BD ϭ Breslow-Day; CI ϭ confidence interval; ERG ϭ electroretinogram; FDA ϭ Food and Drug Administration; IVIg ϭ IV immunoglobulin; LEV ϭ levetiracetam; NZP ϭ nitrazepam; OR ϭ odds ratio; RCT ϭ randomized controlled trial; TPM ϭ topiramate; TRH ϭ thyrotropin-releasing hormone; TSC ϭ tuberous sclerosis complex; UKISS ϭ United Kingdom Infantile Spasms Study; VABS ϭ Vineland Adaptive Behavioral Scale; VGB ϭ vigabatrin; VPA ϭ valproic acid; ZNS ϭ zonisamide.

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“…High intersubject variability as well as intraindividual variations in VPA clearance thus result in a highly variable dose-to-concentration relationship for patients on both mono-and polytherapy (2). In most cases, a lack of data on individual VPA metabolism existed prior to any clinical complications becoming manifest (3).…”

Section: Introductionmentioning

confidence: 99%

Establishing individual metabolite patterns for patients on valproate therapy

Kreher

Darius

Wien

2001

Eur. J. Drug Metab. Pharmacokinet.

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The aim of this study was to establish individual metabolic profiles of patients receiving valproate (VPA) mono- or polytherapy in order to estimate inter- and intraindividual variability under normal conditions. Serum levels of VPA and 15 metabolites were measured by gas chromotography/mass spectrometry (GC/MS) with selected ion monitoring (SIM). Because of a huge inter-subject variability, calculating means for large epileptic populations resulted in broad and vague ranges for serum levels of VPA and its metabolites. It therefore remained difficult to recognize any significant alteration in the individual metabolic profile. Over long term periods, within-patient changes appeared to be much less intense than inherent interindividual differences. In epileptics consecutively receiving various forms of polytherapy, alterations in the metabolic profiles occurred. Therefore, integrating different kinds of co-medication into a single polytherapy group seemed to be inadequate. An adult patient on VPA monotherapy, suffering form intrahepatic metastasis and renal insufficiency, showed an extremely altered metabolic pattern, with the 4-ene and the omega-/omega1-metabolites being strongly elevated and the major beta-metabolites (E)-2-ene and (E,E)-2,3'-diene being significantly diminished. We suggest determining the individual metabolic profile, consisting of accessible major and minor metabolites, for every patient when VPA therapy has been started or been modified. The moment any clinical complications arise, the previously obtained specific pattern of the individual can be taken as reference in order to assess the possible presance of significant alterations which might indicate or even cause any severe side effects. There seems to be no need of monitoring metabolite levels of the average patient continuously except for the high risk group (e.g. infants under 3 years age receiving polytherapy) which exhibited the highest between-subject as well as within-patient variability.

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Valproate Metabolites in Serum and Urine During Antiepileptic Therapy in Children with Infantile Spasms: Abnormal Metabolite Pattern Associated with Reversible Hepatotoxicity

Cited by 47 publications

References 16 publications

Practice Parameter: Medical Treatment of Infantile Spasms

Practice Parameter: Medical Treatment of Infantile Spasms

Evidence-based guideline update: Medical treatment of infantile spasms [RETIRED]

Establishing individual metabolite patterns for patients on valproate therapy

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