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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

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.

ContributorsFrye, Richard E. (Author) / Rossignol, Daniel (Author) / Casanova, Manuel F. (Author) / Brown, Gregory L. (Author) / Martin, Victoria (Author) / Edelson, Stephen (Author) / Coben, Robert (Author) / Lewine, Jeffrey (Author) / Slattery, John C. (Author) / Lau, Chrystal (Author) / Hardy, Paul (Author) / Fatemi, S. Hossein (Author) / Folsom, Timothy D. (Author) / MacFabe, Derrick (Author) / Adams, James (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2013-09-13
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There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing

There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing number of research studies have provided evidence that the composition of the gut (enteric) microbiome (GM) in at least a subset of individuals with autism spectrum disorder (ASD) deviates from what is usually observed in typically developing individuals. There are several lines of research that suggest that specific changes in the GM could be causative or highly associated with driving core and associated ASD symptoms, pathology, and comorbidities which include gastrointestinal symptoms, although it is also a possibility that these changes, in whole or in part, could be a consequence of underlying pathophysiological features associated with ASD. However, if the GM truly plays a causative role in ASD, then the manipulation of the GM could potentially be leveraged as a therapeutic approach to improve ASD symptoms and/or comorbidities, including gastrointestinal symptoms.

One approach to investigating this possibility in greater detail includes a highly controlled clinical trial in which the GM is systematically manipulated to determine its significance in individuals with ASD. To outline the important issues that would be required to design such a study, a group of clinicians, research scientists, and parents of children with ASD participated in an interdisciplinary daylong workshop as an extension of the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism (www.microbiome-autism.com). The group considered several aspects of designing clinical studies, including clinical trial design, treatments that could potentially be used in a clinical trial, appropriate ASD participants for the clinical trial, behavioral and cognitive assessments, important biomarkers, safety concerns, and ethical considerations. Overall, the group not only felt that this was a promising area of research for the ASD population and a promising avenue for potential treatment but also felt that further basic and translational research was needed to clarify the clinical utility of such treatments and to elucidate possible mechanisms responsible for a clinical response, so that new treatments and approaches may be discovered and/or fostered in the future.

ContributorsFrye, Richard E. (Author) / Slattery, John (Author) / MacFabe, Derrick F. (Author) / Allen-Vercoe, Emma (Author) / Parker, William (Author) / Rodakis, John (Author) / Adams, James (Author) / Krajmalnik-Brown, Rosa (Author) / Bolte, Ellen (Author) / Kahler, Stephen (Author) / Jennings, Jana (Author) / James, Jill (Author) / Cerniglia, Carl E. (Author) / Midtvedt, Tore (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-05-07
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Background: Despite the high prevalence of seizure, epilepsy and abnormal electroencephalograms in individuals with autism spectrum disorder (ASD), there is little information regarding the relative effectiveness of treatments for seizures in the ASD population. In order to determine the effectiveness of traditional and non-traditional treatments for improving seizures and influencing other

Background: Despite the high prevalence of seizure, epilepsy and abnormal electroencephalograms in individuals with autism spectrum disorder (ASD), there is little information regarding the relative effectiveness of treatments for seizures in the ASD population. In order to determine the effectiveness of traditional and non-traditional treatments for improving seizures and influencing other clinical factor relevant to ASD, we developed a comprehensive on-line seizure survey.

Methods: Announcements (by email and websites) by ASD support groups asked parents of children with ASD to complete the on-line surveys. Survey responders choose one of two surveys to complete: a survey about treatments for individuals with ASD and clinical or subclinical seizures or abnormal electroencephalograms, or a control survey for individuals with ASD without clinical or subclinical seizures or abnormal electroencephalograms. Survey responders rated the perceived effect of traditional antiepileptic drug (AED), non-AED seizure treatments and non-traditional ASD treatments on seizures and other clinical factors (sleep, communication, behavior, attention and mood), and listed up to three treatment side effects.

Results: Responses were obtained concerning 733 children with seizures and 290 controls. In general, AEDs were perceived to improve seizures but worsened other clinical factors for children with clinical seizure. Valproic acid, lamotrigine, levetiracetam and ethosuximide were perceived to improve seizures the most and worsen other clinical factors the least out of all AEDs in children with clinical seizures. Traditional non-AED seizure and non-traditional treatments, as a group, were perceived to improve other clinical factors and seizures but the perceived improvement in seizures was significantly less than that reported for AEDs. Certain traditional non-AED treatments, particularly the ketogenic diet, were perceived to improve both seizures and other clinical factors. For ASD individuals with reported subclinical seizures, other clinical factors were reported to be worsened by AEDs and improved by non-AED traditional seizure and non-traditional treatments. The rate of side effects was reportedly higher for AEDs compared to traditional non-AED treatments.

Conclusion: Although this survey-based method only provides information regarding parental perceptions of effectiveness, this information may be helpful for selecting seizure treatments in individuals with ASD.

ContributorsFrye, Richard E. (Author) / Sreenivasula, Swapna (Author) / Adams, James (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2011-05-18
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This manuscript reviews biological abnormalities shared by autism spectrum disorder (ASD) and epilepsy. Two neuropathological findings are shared by ASD and epilepsy: abnormalities in minicolumn architecture and γ-aminobutyric acid (GABA) neurotransmission. The peripheral neuropil, which is the region that contains the inhibition circuits of the minicolumns, has been found to

This manuscript reviews biological abnormalities shared by autism spectrum disorder (ASD) and epilepsy. Two neuropathological findings are shared by ASD and epilepsy: abnormalities in minicolumn architecture and γ-aminobutyric acid (GABA) neurotransmission. The peripheral neuropil, which is the region that contains the inhibition circuits of the minicolumns, has been found to be decreased in the post-mortem ASD brain. ASD and epilepsy are associated with inhibitory GABA neurotransmission abnormalities including reduced GABAA and GABAB subunit expression. These abnormalities can elevate the excitation-to-inhibition balance, resulting in hyperexcitablity of the cortex and, in turn, increase the risk of seizures. Medical abnormalities associated with both epilepsy and ASD are discussed. These include specific genetic syndromes, specific metabolic disorders including disorders of energy metabolism and GABA and glutamate neurotransmission, mineral and vitamin deficiencies, heavy metal exposures and immune dysfunction. Many of these medical abnormalities can result in an elevation of the excitatory-to-inhibitory balance. Fragile X is linked to dysfunction of the mGluR5 receptor and Fragile X, Angelman and Rett syndromes are linked to a reduction in GABA[subscript A] receptor expression. Defects in energy metabolism can reduce GABA interneuron function. Both pyridoxine dependent seizures and succinic semialdehyde dehydrogenase deficiency cause GABA deficiencies while urea cycle defects and phenylketonuria cause abnormalities in glutamate neurotransmission. Mineral deficiencies can cause glutamate and GABA neurotransmission abnormalities and heavy metals can cause mitochondrial dysfunction which disrupts GABA metabolism. Thus, both ASD and epilepsy are associated with similar abnormalities that may alter the excitatory-to-inhibitory balance of the cortex. These parallels may explain the high prevalence of epilepsy in ASD and the elevated prevalence of ASD features in individuals with epilepsy.

ContributorsFrye, Richard E. (Author) / Casanova, Manuel F. (Author) / Fatemi, S. Hossein (Author) / Folsom, Timothy D. (Author) / Reutiman, Teri J. (Author) / Brown, Gregory L. (Author) / Edelson, Stephen M. (Author) / Slattery, John C. (Author) / Adams, James (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-05-10
Description

Human Papillomavirus, or HPV, is a viral pathogen that most commonly spreads through sexual contact. HPV strains 6 and 11 normally cause genital warts, while HPV strains 16 and 18 commonly cause cervical cancer, which causes cancerous cells to spread in the cervix. Physicians can detect those HPV strains, using

Human Papillomavirus, or HPV, is a viral pathogen that most commonly spreads through sexual contact. HPV strains 6 and 11 normally cause genital warts, while HPV strains 16 and 18 commonly cause cervical cancer, which causes cancerous cells to spread in the cervix. Physicians can detect those HPV strains, using a Pap smear, which is a diagnostic test that collects cells from the female cervix.

Created2021-04-06
Description

Johann Gregor Mendel studied patterns of trait inheritance in plants during the nineteenth century. Mendel, an Augustinian monk, conducted experiments on pea plants at St. Thomas’ Abbey in what is now Brno, Czech Republic. Twentieth century scientists used Mendel’s recorded observations to create theories about genetics.

Created2022-01-13
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In the 1930s, George Beadle and Boris Ephrussi discovered factors that affect eye colors in developing fruit flies. They did so while working at the California Institute of Technology in Pasadena, California. (1) They took optic discs (colored fuchsia in the image) from fruit fly larvae in the third instar

In the 1930s, George Beadle and Boris Ephrussi discovered factors that affect eye colors in developing fruit flies. They did so while working at the California Institute of Technology in Pasadena, California. (1) They took optic discs (colored fuchsia in the image) from fruit fly larvae in the third instar stage of development. Had the flies not been manipulated, they would have developed into adults with vermilion eyes. (2) Beadle and Ephrussi transplanted the donor optic discs into the bodies of several types of larvae, including those that would develop with normal colored eyes (brick red), and those that would develop eyes with other shades of red, such as claret, carmine, peach, and ruby (grouped together and colored black in the image). (3a) When implanted into normal hosts that would develop brick red eyes, the transplanted optic disc developed into an eye that also was brick red. (3b) When implanted into abnormal hosts that would develop eyes of some other shade of red, the transplanted optic discs developed into eyes that were vermilion. Beadle and Ephrussi concluded that there was a factor, such as an enzyme or some other protein, produced outside of the optic disc that influenced the color of the eye that developed from the disc.

Created2016-10-11
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This illustration shows George Beadle and Edward Tatum's experiments with Neurospora crassa that indicated that single genes produce single enzymes. The pair conducted the experiments at Stanford University in Palo Alto, California. Enzymes are types of proteins that can catalyze reactions inside cells, reactions that produce a number of things,

This illustration shows George Beadle and Edward Tatum's experiments with Neurospora crassa that indicated that single genes produce single enzymes. The pair conducted the experiments at Stanford University in Palo Alto, California. Enzymes are types of proteins that can catalyze reactions inside cells, reactions that produce a number of things, including nutrients that the cell needs. Neurospora crassa is a species of mold that grows on bread. In the early 1940s, Beadle and Tatum conducted an experiment to discover the abnormal genes in Neurospora mutants, which failed to produce specific nutrients needed to survive. (1) Beadle and Tatum used X-rays to cause mutations in the DNA of Neurospora, and then they grew the mutated Neurospora cells in glassware. (2) They grew several strains, represented in four groups of paired test tubes. For each group, Neurospora was grown in one of two types of growth media. One medium contained all the essential nutrients that the Neurospora needed to survive, which Beadle and Tatum called a complete medium. The second medium was a minimal medium and lacked nutrients that Neurospora needed to survive. If functioning normally and in the right conditions, however, Neurospora can produce these absent nutrients. (3) When Beadle and Tatum grew the mutated mold strains on both the complete and on the minimal media, all of the molds survived on the complete media, but not all of the molds survived on the minimal media (strain highlighted in yellow). (4) For the next step, the researchers added nutrients to the minimal media such that some glassware received an amino acid mixture (represented as colored squares) and other glassware received a vitamin mixture (represented as colored triangles) in an attempt to figure out which kind of nutrients the mutated molds needed. The researchers then took mold from the mutant mold strain that had survived on a complete medium and added that mold to the supplemented minimal media. They found that in some cases the mutated mold grew on media supplemented only with vitamins but not on media supplemented only with amino acids. (5) To discover which vitamins the mutant molds needed, Beadle and Tatum used several tubes with the minimal media, supplementing each one with a different vitamin, and then they attempted to grow the mutant mold in each tube. They found that different mutant strains of the mold grew only on media supplemented with different kinds of vitamins, for instance vitamin B6 for one strain, and vitamin B1 for another. In experiments not pictured, Beadle and Tatum found in step (4) that other strains of mutant mold grew on minimal media supplemented only with amino acids but not on minimal media supplemented only with vitamins. When they repeated step (5) on those strains and with specific kinds of amino acids in the different test tubes, they found that the some mutated mold strains grew on minimal media supplemented solely with one kind of amino acid, and others strains grew only on minimal media supplemented with other kinds of amino acids. For both the vitamins and amino acid cases, Beadle and Tatum concluded that the X-rays had mutated different genes in Neurospora, resulting in different mutant strains of Neurospora cells. In a cell of a given strain, the X-rays had changed the gene normally responsible for producing an enzyme that catalyzed a vitamin or an amino acid. As a result, the Neurospora cell could no longer produce that enzyme, and thus couldn't catalyze a specific nutrient.

Created2016-10-12
Description

The Southern Gastric Brooding Frog (Rheobotrahcus silus) was a frog species that lived in Australia. It was declared extinct in 2002. Once adult males fertilized the eggs of females, the females swallowed their eggs. The stomachs of the females then functioned somewhat like wombs, protecting the eggs while they gestated.

The Southern Gastric Brooding Frog (Rheobotrahcus silus) was a frog species that lived in Australia. It was declared extinct in 2002. Once adult males fertilized the eggs of females, the females swallowed their eggs. The stomachs of the females then functioned somewhat like wombs, protecting the eggs while they gestated. Once the eggs developed into juveniles, female frogs performed oral birth and regurgitated their young.

Created2017-02-06