The Epilepsy and Autism Connection
December 08, 2014
By Mark Mintz, M.D. President, CEO & Founder
The Center for Neurological and Neurodevelopmental Health and the Clinical Research Center of New Jersey
Diplomate, American Board of Psychiatry and Neurology (Special Qualification in Child Neurology);
Diplomate, Subspecialty Board of Neurodevelopmental Disabilities;
Diplomate, Subspecialty Board of Epilepsy;
Diplomate, American Board of Pediatrics
Under certain conditions, anyone can experience a seizure. However, individuals with neurodevelopmental disabilities and brain disorders are more prone to developing recurrent seizures, or epilepsy. Why?
What is Epilepsy?
Epilepsy is diagnosed when there are recurrent, unprovoked seizure events. Seizures occur when there is a sudden change in the electrical activity of the brain that disrupts normal brain functions. Seizures can take many forms. The more widely recognized types produce observable events, such as “convulsive” shaking, loss of body control, involuntary movements, and/or loss of awareness or consciousness. However, seizures can also be very subtle, for example disrupting a person’s thought patterns or memory but without noticeable external symptoms. There can also be unexpected “subclinical” electrical changes of the brain (particularly “spikes”), detected by electroencephalography (EEG, a device that records the electrical activity of the brain) monitoring, that are neither noticeable to the individual experiencing this phenomenon nor to observers. Unrecognized and untreated, epilepsy carries a risk of injury from seizures, including trauma, drowning, aspiration, and rarely, sudden unexpected death (SUDEP), as well as unfavorably affecting behavior, development, memory or learning. In those individuals with Autism Spectrum Disorder (ASD), having an associated diagnosis of epilepsy can increase the risk of mortality seven-fold.1
Is There an Autism-Epilepsy Connection?
It has been observed for many years that individuals diagnosed with ASD are at high risk of developing epilepsy. Various studies have placed the risk between 6% to 26% of children and adolescents, with a cumulative risk into the adult years reaching as high as 67%.2 Overall, the risk of epilepsy is higher in ASD if there are associated intellectual disabilities or Cerebral Palsy.3 Why is there this connection? Generally, any brain disorder will increase the predisposition and lower the threshold for generating seizures. Additionally, ASD and epilepsies appear to share common biological and anatomical mechanisms. Advances in biotechnologies have revealed that there are many types of genetic variations causing or contributing to both ASD and the generation of seizures. Innovations in neuroimaging tools and neuropathological studies have revealed “disconnectivity” of various brain circuits leading to both autism and epilepsies. Various prenatal, neonatal and childhood metabolic, infectious and inflammatory disorders have been implicated in both ASD and epilepsy. Thus, understanding the epilepsy-autism connection is providing clues to the causes of ASD.
How is Epilepsy Diagnosed in ASD?
The behavioral and developmental complications of ASD can obscure or mimic the clinical manifestations of seizures; thus, the recognition of seizures is not always apparent in this population. Oftentimes children and adults with ASD do not have classical seizure manifestations. An EEG is necessary to determine if there are clinical or subclinical seizures, or abnormal electrical discharges that might be interfering with brain function or present a high risk for recurrent seizures. Language regression can signify a severe form of an “epileptic encephalopathy” (“Landau-Kleffner” and other related syndromes). Such individuals have very abnormal EEGs, with abnormal electrical patterns worsening with sleep but usually without observable clinical events. Infantile seizures associated with fever can sometimes evolve to autism, and, like other epilepsy syndromes, can be associated with genetic defects of “ion transport” (ions include sodium, calcium, potassium, magnesium). Some individuals with ASD and epilepsy will have “drop attacks” (a sudden loss of motor/body control causing a person to drop their head or fall to the ground) and their EEG will have a specific electrical pattern (“Lennox-Gastaut Syndrome”). Other individuals might only have a staring spell, have unwitnessed seizure events during sleep, or may have classic convulsions.
Overall, since epilepsy is a diagnosable condition with important “actionable” clinical implications, clinical evaluations of individuals with ASD should include screening and assessment of seizure risk and susceptibility. In addition to a comprehensive medical and neurological history and examination, there are other neurodiagnostic tests that a specialist may consider or recommend, including:
- EEG: This device measures the activity of brain cells (“neurons”) in real-time. Conventional EEG can be difficult to obtain in ASD since the application of the approximately 20 electrodes with glues/pastes/scalp abrasion can be traumatic in those with behavioral challenges. Newer “dense-array” EEG technologies allow for application of many more electrodes (128 sponge electrodes) using a specially designed “sensor net” that is applied in minutes without discomfort or risk of infection.
- Neuroimaging: Magnetic Resonance Imaging (MRI) is the study of choice to assess for significant structural abnormalities or malformations of the brain. Other neuroimaging technologies (positron emission tomography [PET], single-photon emission computerized tomography [SPECT], MR Spectroscopy [MRS], diffusion tensor imaging [DTI]) can be useful in select cases.
- Laboratory Evaluations: There are wide arrays of relevant laboratory tests of the blood, urine, and on occasion cerebrospinal fluid (CSF) or skin/muscle tissue, which can help identify a biological cause of epilepsy and/or ASD.
- Genetics: There has been an explosion of the availability of advanced genetic testing technologies, which are transforming the understanding, diagnosis and treatment of epilepsy and ASD. In many cases, the sequencing of thousands of “genes of interest” can be performed on a saliva sample. Genetic testing can also provide information concerning risk, susceptibility and prevention of complications of epilepsy and ASD, sometimes with implications for other family members.
- Neuropsychological Evaluation: Both epilepsy and ASD can have profound effects on neuropsychological function. Neuropsychological evaluations include a series of empirically validated, norm-referenced, and evidence-based tests that quantitatively and qualitatively measure brain function, processing and output.
How is Epilepsy Treated?
Treatment must be individualized and personalized, and include programs to encourage healthy lifestyles (good sleep patterns, nutrition, physical activity, and stress reduction). Therapeutic strategies should target identifiable biological mechanisms and triggers of epilepsy, and simultaneously attempt to relieve seizure burden. Therapies should attend to medical and neurological/neuropsychological complications of epilepsy and/or medications, involve preventative strategies for risk reduction and SUDEP, and provide for a “rescue” plan in cases of acute seizure events. The mainstay for limiting seizure recurrence and promoting spike suppression are antiepileptic drugs (AEDs). In cases of identifiable metabolic and genetic disorders, nutritional supplements or dietary alterations may be indicated. Other options include specific diets such as the ketogenic and related diets (high protein and fat, and minimal carbohydrates), neurostimulation (devices that deliver periodic electrical currents, such as the vagal nerve stimulator [VNS] and other modalities) and “seizure surgery” (the localization and removal of brain tissue identified as the source of seizure generation). Research into the common biological sources of epilepsy and autism may lead to new and novel therapies that propose to alter the course of the disease.
In most cases, epilepsy is a treatable condition. Through proper screening and diagnosis, and the utilization of pragmatic therapies and interventions, the quality of life for children, adolescents and adults who may be suffering from epilepsy and ASD can be improved.
- Pickett J, Xiu E, Tuchman R, et al. Mortality in Individuals with Autism, with and without Epilepsy. J Child Neurol 2011; 26:932-939.
- Amiet C, Gourfinkel-An I, Bouzamondo A, et al. Epilepsy in autism is associated with intellectual disability and gender: evidence from a meta-analysis. Biol Psychiatry 2008; 64:577-582.McVicar KA, Ballaban-Gil K, Rapin I, et al. Epileptiform EEG abnormalities in children with language regression. Neurology 2005; 65:129-131.Suren P, Bakken IJ, Aase H, et al. Autism spectrum disorder, ADHD, epilepsy, and cerebral palsy in Norwegian children. Pediatrics 2012; 130:e152-158.
- Bolton PF, Carcani-Rathwell I, Hutton J, et al. Epilepsy in autism: features and correlates. Br J Psychiatry 2011; 198:289-294.Viscidi EW, Triche EW, Pescosolido MF, et al. Clinical characteristics of children with autism spectrum disorder and co-occurring epilepsy. PLoS One 2013; 8(7):e67797.Woolfenden S, Sarkozy V, Ridley G, et al. A systematic review of two outcomes in autism spectrum disorder – epilepsy and mortality. Dev Med Child Neurol 2012; 54:306-312.