Treatment, Therapy and Management of Metabolic Epilepsy: A Systematic Review

Abstract

Metabolic epilepsy is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals. Commonly used antiepileptic drugs are typically ineffective against metabolic epilepsy as they do not address its root cause. Presently, there is no review available which summarizes all the treatment options for metabolic epilepsy. Thus, we systematically reviewed literature which reported on the treatment, therapy and management of metabolic epilepsy from four databases, namely PubMed, Springer, Scopus and ScienceDirect. After applying our inclusion and exclusion criteria as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed a total of 43 articles. Based on the reviewed articles, we summarized the methods used for the treatment, therapy and management of metabolic epilepsy. These methods were tailored to address the root causes of the metabolic disturbances rather than targeting the epilepsy phenotype alone. Diet modification and dietary supplementation, alone or in combination with antiepileptic drugs, are used in tackling the different types of metabolic epilepsy. Identification, treatment, therapy and management of the underlying metabolic derangements can improve behavior, cognitive function and reduce seizure frequency and/or severity in patients.

Effects of valproic acid on skeletal metabolism in children with epilepsy: a systematic evaluation and meta-analysis based on 14 studies

“…In addition to the influence of nutritional status, the metabolism of the skeletal system in children is also affected by multiple factors such as chronic disease, drugs, and outdoor exercise time [24,25]. Valproic acid has been used as one of the traditional agents to control epileptic seizures in children [2,13]. As early as 2003, one…”

“…Although antiepileptic drugs (AEDs) do not have a "curative effect" on epilepsy, they control seizures. Valproic acid has been widely used as a long term anti epileptic medication [2], as it displays a certain effects in absence seizures, clinical depression, tonic-clonic seizures, juvenile myoclonic epilepsy and complex partial seizures [3,4].…”

“…Cytochrome P450 (CYP450) isozyme can be induced by AEDs such as carbamazepine, phenytoin sodium, phenobarbital and valproic acid, which may lead to vitamin D deficiency, hypocalcemia, increased fracture risk [6]. Opinions suggest that long-term use of this drug may have an impact on bone metabolism in children [1][2][3]7]. We performed a meta-analysis to determine the effects of valproic acid on bone metabolism and bone mineral density (BMD) in epileptic children.…”

Mini-review on the psychiatric comorbidities in epilepsy – possible relevance for some metabolic changes?

“…When it comes to the relations between epilepsy and metabolism, there are reports and extensive reviews in the literature on the so-called "Metabolic Epilepsy", which is defined by the Lee group in 2018 as "is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals" (64). Even more important, as the above authors are describing, it seems that the commune drugs used for treating "normal" epilepsy, are not working in this case, since the mechanistics behind these two are quite different (64). It also seems that diet could be playing an important part in the management of this specific disorder (65).…”

“…It also seems that diet could be playing an important part in the management of this specific disorder (65). In fact, in an extensive recent review no less than 14 main mecanistical causes were identified such as: biotinidase deficiency, cerebral folate deficiency, creatine-related disorders, disorders of the urea cycle, folinic acid-responsive seizures, glucose transporter type 1 deficiency syndrome, glutaric aciduria, mitochondrial disorders, molybdenum cofactor deficiency, non-ketotic hyperglycaemia, peroxisomal-related disorders, pyridoxine-dependent epilepsy/ pyridox(am)ine-5′-phosphate oxidase-related deficiency and succinic semialdehyde dehydrogenase (SSADH) Deficiency (64).…”