Autism & Epilepsy

Autism & Epilepsy: Is There A Relationship?

An Amazing Yearly Conference & Resource ~ Epilepsy Awareness Day at Disneyland Resort ~ EADDL

The Following information is from the Epilepsy Foundation & TACA ~ The Autism Community Action

What is Epilepsy?

• Seizures: abnormal electrical firing from the brain

• Epilepsy: recurrent seizures

• Approximately 1-2% of children are diagnosed with epilepsy

What is Autism Spectrum Disorders?

• Autism Spectrum Disorders (ASD): developmental dysfunction involving social, speech, cognition and behavioral disabilities

• About 0.1% of children have ASD worldwide

• In the United States, about 1.5% of children have ASD

Is there a connection?

• Yes, there is an association between epilepsy and autism.

• Children with autism are (a little) more likely to have epilepsy.

• Children with epilepsy are (a little) more likely to have autism.

• Seizures are the most common neurologic complication in ASD.

Do all children with autism have seizures?

• No. Not all autistic children will develop seizures. In fact, only a minority will.

• Similarly, not all children with epilepsy will have autism. Only a small minority.

• Approximately a third of the autistic spectrum also have epilepsy.

Are some people with ASD more prone to seizures than others?

• Yes, some genetic disorders are associated with both seizures and autism, including Rett’s, Fragile X, Angelman, Prader-Willi and many other syndromes.

• Children with characteristics that suggest these disorders should undergo genetic testing.

Is there a specific type of seizure associated with ASD?

• No, there is no one type of seizure in ASD.

• Seizures can be focal or generalized.

• Includes focal onset impaired awareness (complex partial), absence, tonic-clonic, and atonic just to name a few.

Types of Seizures

There are two broad types of seizures: generalized and focal (partial). Below is a brief description of each.

Generalized Seizures

Generalized seizures affect both sides of the brain. There are two types of generalized seizures:

• Absence seizures (petit mal): can cause a person to blink rapidly, stare out into space, or lose focus for a few seconds.

• Tonic-clonic seizures (grand mal): is one of the most severe types of clinical seizures where the entire brain can demonstrate abnormal electrical activity.

• When most people think of seizures, they think of generalized tonic-clonic seizures in which the whole body shakes rhythmically, and there is a loss of consciousness.

• While most tonic-clonic episodes last less than 5 minutes, they can be dangerous if they continue for 15 minutes or more.

Focal (Partial) Seizures

In focal (partial) seizures, only one part of the brain experiences abnormal electrical activity.

• Focal seizures can be very subtle, manifesting only as staring episodes or they might have no visible signs to indicate that a seizure is happening.

• Or, they can cause one part of the body, such as an arm or leg, to demonstrate rhythmic movement.

• Ultimately, how a focal seizure looks and feels depends on which area of the brain the seizure activity occurs because different parts of the brain are responsible for specific functions and sensations.

It is important to note that a seizure can begin as a focal seizure, in one part of the brain, and progress to a generalized seizure, affecting both sides of the brain.

Are seizures in people with ASD more severe?

• Generally no, but it is variable.

• Some seizures are easily controlled and others are intractable.

• There is higher mortality and morbidity (rate of disease) associated with seizures in ASD.

Seizures in Autism

Seizures are relatively common among individuals with autism spectrum disorders (ASD). While 1-2% of children in the general population develop epilepsy, the prevalence of epilepsy in ASD is much higher, with estimates varying from 5% to 38%.

Some individuals with ASD develop seizures in childhood, some at puberty, and some in adulthood. Although the prevalence of seizures by age is not well studied, recent studies suggest the risk remains high into adulthood.

It is noteworthy that specific subgroups within autism have a higher risk of developing seizures and epilepsy. Namely, individuals with comorbid intellectual disabilities, genetic abnormalities, and/or brain malformations.

The most concerning issue is the association between seizures with the increased mortality and morbidity among individuals with autism. For adults with autism, they are the leading cause of premature death.

Diagnosing Seizures in Autism

Seizures can be challenging to diagnose in autism. This is because overlapping symptoms (e.g., staring episodes, motor tics, and stereotyped movements) make it difficult to differentiate between the subtle signs of seizures and the characteristics of autism. Nevertheless, it is important to determine if these symptoms can be attributed to seizures or another neurological abnormality because they are treated very differently.

When it is unclear if a symptom is or isn’t being caused by a seizure, an extended, overnight, or 24-hour electroencephalogram (EEG) should be performed. Because EEGs provide a continuous recording of the brain’s electrical activity, they allow you to capture what is going on in the brain during suspicious behaviors.

Many doctors recommend a 24- to 48-hour EEG to gather needed information during both wakefulness and sleep. Ultimately, obtaining an extended EEG will increase your chance of getting a clear and accurate diagnosis.

Sub-Clinical Electrical Discharges

Individuals with ASD have a high rate of seizure-like activity when their brain waves are measured with an electroencephalogram. These are referred to as sub-clinical electrical discharges. The significance of these abnormalities is not clear as they rarely result in symptoms of seizure. However, some research studies associate them with cognitive dysfunction in children with epilepsy.

Furthermore, these seizure-like discharges are associated with specific epileptic syndromes that share characteristics with ASD, such as Landau-Kleffner Syndrome and Continuous Spike-wave Activity during Slow-wave Sleep.

Early research suggests that anti-epileptic medications may improve cognitive, behavioral, or psychiatric symptoms for individuals with sub-clinical discharges.

Causes of Seizures in Autism

Conditions that can trigger seizures in individuals (with or without ASD) include head injuries, infection or inflammation affecting the brain (e.g., encephalitis), ingestion or withdrawal from certain medications or recreational drugs, and disturbances of electrolyte levels.

Additionally, there is an association between specific genetic and metabolic syndromes and both ASD and seizures. For this reason, every child with ASD and seizures should have a comprehensive medical evaluation for known medical disorders that includes the following:

• A genetic workup, consisting of a chromosomal microarray, Fragile X, and Rett syndrome testing

• If these return normal, further testing may include an epilepsy genetic panel or whole exome genetic sequencing.

• Genetic testing for the following syndromes (if your child has certain dysmorphic features or characteristics):

• Tuberous Sclerosis Complex, Angelman, Prader–Willi, Velocardiofacial, and Smith-Lemli-Opitz syndromes

• Testing for Mitochondrial Dysfunction and Cerebral Folate Deficiency, metabolic disorders with a high prevalence among individuals with ASD and seizures

• If supporting clinical characteristics exist, consider testing for other, much more rare metabolic disorders, such as:

• Succinic Semialdehyde Dehydrogenase Deficiency, Adenylosuccinate lyase deficiency, Creatine Metabolism Disorder, Phenylketonuria, Pyridoxine dependent and responsive seizures, and Urea Cycle Disorders

What should parents look for?

• It may be difficult to recognize seizure activity in ASD, because of the communication barriers and overlap of symptoms with frequent abnormal behaviors.

• For example, repetitive purposeless behaviors of autism can resemble automatisms seen in seizures.

• Cognitive delay, impaired social interactions, and aggressive and irritable behavior seen in children with epilepsy can also be seen with ASD, thus it is difficult to discern the cause.

• Red flags to note for seizures:

• Staring episodes (which could be signs of absence or atypical absence seizures)

• Stiffening (which could be a sign of tonic seizures)

• Rhythmic shaking or twitching (which could be a sign of focal aware/simple partial seizures)

• Loss of attention (which could be a sign of absence or focal impaired awareness/complex partialseizures)

What can be done?

Epilepsy associated with ASD does not change the evaluation or management of seizures.

• Medical evaluation with brain imaging and EEG (electroencephalogram)

• Anti-epileptic drugs for treatment

• Adjunctive non-pharmacologic therapy can be considered if medications fail (ketogenic diet, vagus nerve stimulation)

• Safety measures by caregivers: avoid restraining child, move large objects from area to avoid injury, turn child on his or her side, ensure nothing in mouth to avoid choking. Learn more care and comfort first aid.

Treatment Options for Seizures

Seizures are most commonly treated with anti-epileptic drugs (AEDs), but non-AED treatments are also available. If a specific genetic or metabolic syndrome is associated with seizures in a child with ASD, there may be a specific treatment for that underlying condition. However, for the most part, AEDs are necessary to control seizures–even in children where an underlying genetic or metabolic disorder has been identified.

Below you will find information about AED, non-AED, and emergency treatment options for seizures.

Anti-Epileptic Drugs (AEDs)

Although AEDs are first line for treating seizures, no AED has undergone evaluation for efficacy for the treatment of seizures in the ASD population. Recently, to determine whether specific treatments were more beneficial than others for individuals with ASD and seizures, 733 parents of children with ASD and seizures were asked to rate the effect of AEDs on seizures and other clinical factors including sleep, communication, behavior, attention and mood. The results of the ratings appear to confirm the clinical experience of many clinicians:

• Out of all AEDs examined, four provided the best seizure control and worsened other clinical factors the least:

• Valproate, Lamotrigine, Levetiracetam, and Ethosuximide

• Specifically, Valproate and Lamotrigine had the least detrimental effect on mood, and Lamotrigine appeared to have the least overall adverse effects.

Adverse Effects of Specific AEDs

When taking AEDs, it is common for individuals to experience one or more of the following:

• Neurological side-effects (i.e., ataxia, tremor, nystagmus)

• Behavioral side-effects (i.e., hyperactivity, agitation, aggressiveness)

• Gastrointestinal side-effects (i.e., abdominal pain, nausea)

• Some AEDs can cause an allergic reaction, which can be severe in some cases.

Specific adverse effects are highly dependent on the medication. Overall, newer AEDs, such as Lamotrigine, Oxcarbazepine, Topiramate, and Levetiracetam, have fewer serious adverse effects than older AEDs Phenobarbitol, Phenytoin, Primidone, and Carbamazepine. The exception to this is Valproate, an older anti-epileptic medication that appears to have good efficacy for many individuals with ASD. Still, Valproate does have some severe side effects (see more below).

In general, it is best to avoid older AEDs (Phenobarbitol, Phenytoin, Felbamate). They have a high incidence of cognitive and neurological adverse effects, which can exacerbate existing behavioral and cognitive abnormalities.

You can avoid serious side effects with careful monitoring. For this reason, it is best to have an experienced practitioner prescribe AED medications and monitor the patient. Particular care should be taken when using multiple AEDs as adverse effects can be cumulative. Since many AEDs elevate the risk of congenital disabilities, it is important to carefully consider the choice of AEDs in females of childbearing age.

Below is a guide to selecting AEDs followed by information about the adverse effects of specific AEDs. Please note, adverse effect profiles have not been studied in ASD specifically, so it is unknown whether individuals with ASD have a higher incidence of adverse effects than other populations of individuals with epilepsy.