Reversible altered consciousness with brain atrophy caused by valproic acid

Yamanouchi, Hideo; Ota, Takako; Imataka, George; Nakagawa, Eiji; Eguchi, Mitsuoki

doi:10.1016/s0887-8994(03)00005-5

Cited by 11 publications

(7 citation statements)

References 9 publications

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“…Another important point is the possible effects of prophylactic treatments used for CM on the brain volume. There are numerous anecdotal case reports with reversible brain atrophy related to valproate treatment in patients with epilepsy, bipolar disorder and dementia in various age groups (39)(40)(41)(42)(43)(44)(45). The mechanism of this rarely observed side effect underlying these brain changes is poorly understood and it was not reported for migraineurs before.…”

Section: Discussionmentioning

confidence: 99%

Volumetric differences suggest involvement of cerebellum and brainstem in chronic migraine

et al. 2015

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CM patients showed significant volume differences in infratentorial areas and white-matter abnormalities in the posterior part of the brain. It is currently unclear whether the structural brain changes seen in migraine patients are the cause or the result of headaches. Longitudinal volumetric neuroimaging studies with larger groups, especially on the chronification of migraine, are needed to shed light on this topic.

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Section: Discussionmentioning

confidence: 99%

Volumetric differences suggest involvement of cerebellum and brainstem in chronic migraine

et al. 2015

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“…24,25 Even in the absence of frank valproate-induced hyperammonemic encephalopathy, there are reports of reversible cognitive deficits associated with VPA use. 7,10 One prospective study of 36 epilepsy patients (age ranging from 22 to 74) with VPA levels in the normal therapeutic range reported an 86% incidence of cognitive impairment, with degree of cognitive adverse effects highly associated with increased age. A total of 72% improved after discontinuing VPA.…”

Section: Discussionmentioning

confidence: 99%

Chronic divalproex sodium use and brain atrophy in Alzheimer disease

et al. 2011

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Objective:We evaluated the effect of the divalproex sodium formulation of valproic acid on brain volumes using MRI in people with mild to moderate Alzheimer disease (AD) and assessed for changes associated with behavioral and cognitive effects.Methods: Eighty-nine of 313 participants randomized to divalproex or placebo in a 24-month, parallel-group trial received MRI scans at baseline and 12 months. Interval MRI annual percent changes in whole brain, ventricular, and hippocampal volumes were the primary outcomes of interest. Change from baseline in clinical outcomes was assessed at 6-month intervals.Results: There were no baseline differences between active treatment and placebo groups in age, education, brain volumes, clinical rating scores, or APOE ⑀4 carrier status. The group treated with divalproex showed a greater rate of decline in left and right hippocampal and brain volumes (Ϫ10.9% and Ϫ12.4% vs Ϫ5.6% and Ϫ6.3%, and Ϫ3.5% vs Ϫ1.4%, respectively), and a greater rate of ventricular expansion (24.5% vs 9.9%) (p Ͻ 0.001). Mini-Mental State Examination scores showed a more rapid decline with divalproex through month 12 (placebo ϭ Ϫ2.0 Ϯ 4.3, divalproex ϭ Ϫ3.9 Ϯ 4.0) (p ϭ 0.037), although there were no changes on other cognitive, behavioral, or functional ratings at 12 and 24 months.

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“…The finding is open to interpretation; however, there are reports of reversible brain atrophy and cognitive impairment in children and young adults, [41][42][43][44] and the drug prescribing information states: "Reports have noted reversible cerebral atrophy and dementia associated with valproate therapy." These reported effects of valproate on brain volumes of individuals with AD are not well understood; it is unclear if they may be due to direct drug effects, such as osmotic shifts or metabolic toxicity, [41][42][43][44][45] or influences on AD pathology, and it is unknown whether these effects are reversible or clinically relevant. The results of this trial, along with inconclusive results of preliminary trials as well as subsequent negative findings from a large trial, 46 should discourage prophylactic or symptomatic use of valproate in dementia.…”

Section: Commentmentioning

confidence: 99%