Abstract
Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD), the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs) have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine, and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections, immunomodulation, and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports l-carnitine, multivitamins, and N-acetyl-l-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet, and low-frequency repetitive transcranial magnetic simulation. Zinc and l-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use of these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD are warranted.
Highlights
TREATMENTS FOR SEIZURES IN GENETIC AND METABOLIC SYNDROMES ASSOCIATED WITH AUTISM SPECTRUM DISORDER This review examined treatments for specific syndromes associated with autism spectrum disorder (ASD) and seizures, including genetic syndromes such as TSC and Fragile X and metabolic disorders such as mitochondrial disease and dysfunction, urea cycle disorder, succinic semialdehyde dehydrogenase, branched-chain ketoacid dehydrogenase kinase, creatine and biotinidase deficiency, Smith–Lemli–Opitz syndrome, pyridoxine-dependent and responsive seizures, organic acidemias, and abnormalities of folate and cobalamin metabolism
This review suggests that certain novel treatments, such as Mg with pyridoxine, omega-3 fatty acids, the gluten-free casein-free (GFCF) diet, and lowfrequency repetitive transcranial magnetic simulation could be useful for the treatment of seizures and ASD symptoms while other treatments such as Zn and l-carnosine hold some promise
Determining the underlying medical etiology of seizures will assist in directing specific treatment
Summary
A number of studies suggest that seizures affect a high propor- symptoms. tion of children with autism spectrum disorder (ASD). We considered treatments associated with metabolic and genetic disorders that are commonly found in children with ASD and seizures. Since seizures in ASD are associated with specific genetic and metabolic syndromes, therapies that target these syndromes may augment traditional treatments. Since seizures in ASD are associated with specific genetic and metabolic syndromes, therapies that target these syndromes are reviewed as they may augment traditional treatments (see Treatments for Specific Syndromes). There is a high prevalence of the use of novel treatments in ASD individuals with and without seizures [10] and in the general ASD population [11], novel treatments that have the potential to improve seizures are reviewed (see Novel Treatments). Using a well-established scale [14], each study was individually assessed to determine the level of evidence, ranging from Level 1 to 5
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