EEGs Offer Insights for Autistic Children with or without Epilepsy

EEGs Offer Insights for Autistic Children with or without Epilepsy

Abnormal electroencephalography (EEG) results or epilepsy in patients with autism suggest worsening development and adaptive functioning, according to new findings.

Researchers from Cincinnati Children’s Hospital Medical Center studied 443 patients with autism in order to determine the relationship between epilepsy presence and/or abnormal EEG results and impairments linked to autism in young children. The researchers classified the participants into 3 groups: autism without epilepsy but with irregular EEG results, autism without epilepsy and with normal EEG results, and autism with epilepsy.

The researchers collected data about birth and medical history, developmental history, medications, and medical comorbidities while the subjects underwent developmental and language assessments. The investigators also gathered information about EEG results such as presence, characterization, and location of abnormalities.

There were 70 patients diagnosed with epilepsy at the time of autism diagnosis, the researchers said. The remaining patients did not have epilepsy at the time of autism diagnosis, and, of those, a quarter had abnormal EEG results, according to the study authors. One third of the abnormalities were epileptiform, the other third were “other” abnormalities. Most of the epileptiform dischargers were focal and most commonly found in the temporal region of the brain.

The researchers observed that the patients with abnormal EEG results demonstrated more impaired adaptive functioning when compared against the group with normal EEG results, they said. Plus, the abnormal EEG results group was similar to the epilepsy group, the researchers learned, but there were some differences in expressive language and fine motor skills.

The epilepsy group showed lower scores in all developmental and adaptive functioning measures compared to the group with normal EEG results, they added. All 3 groups showed high rates of receptive and expressive language scores in the moderate-to-severe range of impairment, but language differences were expected in all 3 of the groups.

“I think the most surprising findings were that kids with the abnormal EEGs and no seizures appeared more similar to kids with epilepsy in terms of adaptive functioning,” study author Jamie K. Capal, MD told MD Magazine®. “There is a lot of debate as to what to do with kids with [autism] and abnormalities on EEG but no history of seizures. Many neurologists do not treat abnormalities on EEG in the absence of seizures. This finding supports the idea that the abnormalities on EEG have a clinical effect, which could open the doors for treatment interventions.”

Photo: Jamie Capal, MD

While several studies have shown that intellectual disability is an independent risk factor in the development of epilepsy in patients with autism, the study authors wrote, the results of their study showed that patients with epilepsy alone demonstrated lower cognitive and adaptive functioning compared to other groups. Some of these children with epilepsy had moderate-to-profound ranges of impairment, especially expressive and receptive language. About a quarter of children with epilepsy but without autism have intellectual disability, and the highest prevalence is with children who have seizure onset at an earlier age.

 

“The results of our study show evidence that in the setting of [autism], children with abnormal EEG results without seizures are more similar to children with epilepsy than to those without abnormal findings on EEG,” the study authors concluded. “These results have important implications on future research in this area and demonstrate the need for prospective studies that collect EEG data as part of the standard work-up for [autism] regardless of concern for seizure, as well as the need for longitudinal studies to determine the predictive value of an abnormal EEG result in the development of later epilepsy.”

The paper, “EEG endophenotypes in autism spectrum disorder,” was published in Epilepsy & Behavior.

SOURCE: MD Magazine(R)

What does autism look like in the brain?

What does autism look like in the brain?

People on the autism spectrum often dislike exposure to unexpected stimuli, but why is that? New research takes a look at what happens in the brain, and how that relates to a person’s ability to tolerate exposure to various stimuli.  
What happens in the brains of people with autism?

 

“People with autism do not like unexpected stimuli, and it may be because brains are not as efficient at rapidly shifting between ideas or thoughts,” notes Dr. Jeff Anderson, a professor in Radiology at the University of Utah Health in Salt Lake City.

Recently, Dr. Anderson and colleagues decided to try and gain a better understanding as to why individuals with autism may experience some of their symptoms.

To do so, they directed their attention to the complex circuitry of the human brain. “We wondered if we could see how local circuits in the brain react in patients with autism,” explains the researcher.

The research team reports the findings of their study in the journal JAMA Network Open. The full study paper is available online.

 

Overly persistent brain connections

First, the researchers conducted functional MRI (fMRI) scans on 90 male participants, of which 52 had a diagnosis of autism and 38 did not. The participants with autism were aged between 19 and 34, while the rest of the volunteers — who acted as the control group — had ages ranging between 20 and 34.

Then, to confirm the initial findings, the specialists compared their data with that collected from a further 1,402 people who participated in the Autism Brain Imaging Data Exchange (ABIDE) study. Of these, 579 participants (80 female and 499 male) had autism. The remaining 823 participants (211 female and 612 male) did not have autism and acted as the control group.

 

Dr. Anderson and team used a novel fMRI method to explore brain activity in the participants on the current study. More specifically, they looked at the duration of connections established across brain regions.

“We don’t have good methods for looking at the brain on these timescales. It’s been a blind spot because it falls in between typical MRI and [electroencephalogram] studies,” explains Dr. Anderson.

Thanks to the fMRI scans, the researchers were able to confirm that in the brains of people with autism, connections persist for more extended periods than they do in the brains of neurotypical individuals. In other words, in autism, the brain finds it harder to switch between processes.

In those with autism, brain connections remained synchronized for up 20 seconds, while they disappeared faster in individuals without this condition. Moreover, in those with autism, symptom severity appeared to increase with connectivity duration.

‘A whole new perspective’

These findings, which were consistent with data from the ABIDE study, may explain why people with autism can experience distress when exposed to numerous stimuli at once, the research team believes.

“Individuals with autism who have greater social dysfunction have an increase in synched activity in their scans,” notes postdoctoral researcher Jace King, first author of the study paper.

“Now that we are looking at finer timescales, we’ve found a consistent story. It provides us with new tools to figure out the mechanisms that may underlie autism,” King adds.

Nevertheless, the researchers note that their study faced one fundamental limitation — namely that it worked with male participants only, which may not offer the full picture of what characterizes autism in the brain. Still, they will not stop at this study and hope to expand this research.

We want to compare the results from this analysis to more traditional methods. This is a whole new perspective into how autism works in the brain and can help us develop strategies for treatment and finding medications that might be more effective to ease the symptoms of the disorder.”

Dr. Jeff Anderson

SOURCE: Medical News Today By M. Cohut

Reversing autism with a cancer drug

Reversing autism with a cancer drug

Researchers may have found a promising new treatment for a genetic form of autism. Using experimental cancer drugs, scientists reversed the condition in mice.

 

It may soon be possible to reverse and even prevent autism.

(more…)

Early-Life Seizures Prematurely Wake Up Brain Networks Tied to Autism

Early-Life Seizures Prematurely Wake Up Brain Networks Tied to Autism

Antiepileptic Drug May Keep Synapses ‘Silent’ Longer So Brain Can Develop Normally, Penn Study Suggests

 

Early-life seizures prematurely switch on key synapses in the brain that may contribute to further neurodevelopmental delay in children with autism and other intellectual disabilities, suggests a new study from researchers at Penn Medicine published online in Cell Reports. Importantly, the study shows that an existing targeted therapy may keep those synapses “silent” after seizures to allow the brain to develop normally during a critical time in a person’s life. “Silent” synapses become active with experience, and removal of the reservoir of these synapses due to seizures results in a decreased capacity to engage these synapses in later learning.

 
Seizures from epilepsy early on in life have been linked to autism and other disorders—up to 40 percent of children with autism have epilepsy, for instance. However, mechanisms behind that relationship have been less understood. What is known is that early development of the brain involves a series of “critical periods” where synapses tied to learning and language skills are gradually activated. Seizures can lead to learning and cognition issues, past research has shown, but how they affect the critical periods of development remained unknown until now.

 
“Understanding the precise synaptic changes following seizures gives an opportunity to find treatments that can prevent this early ‘unsilencing,’” said senior author Frances E. Jensen, MD, chair of the department of Neurology and a professor of Neurology in the Perelman School of Medicine at the University of Pennsylvania. “The timing is important: We need to stop it right after the seizures and before a critical period of development in a child’s life so the brain can develop without any problems that may lead to future impairments.”

 
According to recent estimates from the Centers for Disease Control and Prevention, about one in 60 children in the United States has autism. Up to 40 percent of children with autism and intellectual disabilities also suffer from epilepsy, and approximately 35 percent of children with infantile spasms develop long-term intellectual disabilities, including autism.

 
In preclinical studies, the team discovered that following induced seizures “silent” thalamocortical synapses in the auditory cortex containing only NMDA receptors switched to “unsilent” synapses with both NMDA and AMPA receptors. Thalamocortical pathways are the main route of sensory information to the cerebral cortex, and the NMDA and AMPA receptors play important roles in learning and forming new memories. This premature activation of the synapses with the additional AMPA receptor is what created a disruption in the auditory synapses days later during the critical period of development in mice, they found.

 
The researchers induced seizures in mice with pentylenetetrazol, or PTZ, injections and used voltage-sensitive dye (VSD) imaging to monitor, measure, and visualize brain activity in the auditory cortex.

 
Next, the researchers investigated what impact an AMPA receptor antagonist, an antiepileptic and anticonvulsant drug known as NBQX, would have on the synapses because past studies had shown that inactivation of AMPA receptors with the drug had prevented seizure-induced changes in the neurons of the hippocampus.

 
In seizure-induced mice, NBQX treatment reduced AMPA receptor enhancement and premature “unsilencing” of the thalamocortical synapses, and also restored synaptic plasticity during the critical period, the researchers reported. Control mice injected with saline after seizures showed impaired synaptic plasticity, which was consistent with the prior observations.

 
The new findings reveal a mechanism for the relationship between seizures and later-in-life cognitive impairment, as well as a much-needed potential treatment avenue to pursue.
“This is proof of principle that synaptic plasticity is a dynamic target for the treatment of autism and intellectual disabilities that accompany early-life seizures,” Jensen said. “Further exploration will not only gain more insight into the etiology and treatment of autism, but also other neurodevelopmental disorders.”

Photo Credit: Penn Medicine
Photo of Frances E. Jensen, MD

Study co-authors include Hongyu Sun and Jocelyn J. Lippman-Bell from Penn, Ting Ting Wang, from Carleton University, and Anne E. Takesian and Takao K. Hensch, from Harvard University.
This work was supported by the National Institutes of Health (NS 031718, DP1 OD003347, P30 HD18655, DP1OD003699, and NS080565-01A1), the Canadian Institute for Advanced Research, Carleton University, a Natural Sciences and Engineering Research Council of Canada Q1 Discovery Grant (RGPIN06552), and the Nancy Lurie Mark Family Foundation.

 

Source: newswise.com –  Perelman School of Medicine at the University of Pennsylvania 

 

Can Marijuana Treat Autism? These Clinical Trials Aim to Find Out

Can Marijuana Treat Autism? These Clinical Trials Aim to Find Out

A growing number of clinical trials are looking into whether compounds in marijuana can be used to treat some of the symptoms of autism.

 
One of these clinical trials was just announced at the University of California, San Diego, and others are slated to take place in New York at Montefiore Medical Center and New York University, and in Israel at Shaare Zedek Medical Center.

 

These trials were prompted, in part, by the success of other clinical trials investigating whether cannabis could effectively and safely treat other neurological disorders, including two rare forms of epilepsy and a condition called fragile X syndrome. [7 Ways Marijuana May Affect the Brain] (more…)

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